Molecular-Iodine-Catalyzed One-Pot Synthesis of 1,5-Benzodiazepine Derivatives under Solvent-Free Conditions

Abstract

2,3-Dihydro-1H-1,5-benzodiazepines have been syn­thesized from o-phenylenediamine (OPDA) and ketones under ­solvent-free conditions in the presence of a catalytic amount of ­molecular iodine. All of the ketones, including cyclic ketones and acyclic ketones, reacted smoothly with OPDA to furnish products. Compared to other reaction conditions, this new protocol has the ­advantage of excellent yield and short reaction time at room temperature.

benzodiazepine - o-phenylenediamine - iodine - ketones - solvent-free

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21

General Experimental Procedure: A mixture of OPDA (1 mmol), ketone (2 mmol), and iodine (0.1 mmol) were ground together in a mortar with a pestle at room temperature for several minutes. After completion of the reaction (TLC), the reaction was treated with aqueous Na₂S₂O₃ to furnish the crude products, which were further purified by column chromatography.
3a: Mp 145-146 °C. IR (KBr): 3341, 1637, 1600 cm^-1. ¹H NMR (CDCl₃): δ = 1.37 (s, 6 H), 2.25 (s, 2 H), 2.39 (s, 3 H), 3.44 (br s, 1 H), 6.64-7.41 (m, 4 H). ¹³C NMR (CDCl₃): δ = 29.4, 30.8, 44.9, 68.1, 121.6, 122.3, 126.1, 126.8, 138.2, 140.9, 171.6.
3b: Mp 137-138 °C. IR (KBr): 3328, 1640, 1608 cm^-1.¹H NMR (CDCl₃): δ = 0.98 (t, 3 H, J = 6.8 Hz), 1.24 (t, 3 H, J = 7.1 Hz), 1.72 (q, 2 H, J = 6.8 Hz), 2.18 (m, 2 H), 2.34 (s, 3 H), 2.71 (q, 2 H, J = 7.1 Hz), 3.28 (br s, 1 H), 6.78-7.33 (m, 4 H). ¹³C NMR (CDCl₃): δ = 8.8, 11.2, 26.8, 35.9, 36.0, 42.3, 70.8, 121.9, 125.2, 126.4, 126.8, 137.6, 140.9, 175.8.
3c: Mp 142-144 °C. IR (KBr): 3320, 1638, 1596 cm^-1.¹H NMR (CDCl₃): δ = 0.81-1.15 (m, 10 H), 1.22-1.42 (m, 4 H), 1.52-1.66 (m, 2 H), 2.38-2.56 (m, 2 H), 2.91 (q, 1 H, J = 7.0 Hz), 3.78 (br s, 1 H), 6.56-7.38 (m, 4 H). ¹³C NMR (CDCl₃): δ = 7.6, 7.9, 11.9, 12.4, 28.1, 28.5, 35.5, 46.4, 68.4, 117.6, 118.2, 126.4, 132.7, 139.1, 142.2, 173.9.
3d: Mp 118-120 °C. IR (KBr): 3265, 1651, 1600 cm^-1. ¹H NMR (CDCl₃): δ = 0.96-1.085 (m, 12 H), 1.34 (s, 3 H), 1.50-1.52 (m, 2 H), 1.66-1.75 (m, 1 H), 2.07-2.26 (m, 3 H), 2.25 (d, 2 H, J = 12.7 Hz), 6.60-7.15 (m, 4 H). ¹³C NMR (CDCl₃): δ = 22.6, 22.9, 24.1, 24.8, 25.1, 26.2, 28.3, 43.4, 51.7, 51.9, 70.9, 121.4, 121.5, 125.3, 127.4, 137.9, 140.5, 173.9.
3e: Mp 150-152 °C. IR (KBr): 3268, 1640, 1601 cm^-1. ¹H NMR (CDCl₃): δ = 1.81 (s, 3 H), 3.01 (d, 1 H, J = 12.8 Hz), 3.16 (d, 1 H, J = 12.8 Hz) 3.45 (br s, 1 H), 6.56-7.02 (m, 3 H), 7.14-7.40 (m, 7 H), 7.56-7.65 (m, 4 H). ¹³C NMR (CDCl₃): δ = 29.8, 42.9, 73.5, 121.2, 121.5, 125.3, 126.1, 126.7, 126.9, 127.8, 128.2, 128.5, 129.6, 137.9, 139.4, 139.9, 147.5, 167.6.
3f: Mp 141-143 °C. IR (KBr): 3270, 1644, 1602 cm^-1. ¹H NMR (CDCl₃): δ = 2.11 (s, 9 H,), 3.05 (d, 1 H, J = 13.6 Hz), 3.17 (d, 1 H, J = 13.6 Hz,), 3.60 (br s, 1 H), 7.12-7.61 (m, 11 H). ¹³C NMR (CDCl₃): δ = 21.3, 24.4, 28.4, 29.0, 46.4, 52.5, 114.7, 122.2, 126.2, 127.1, 128.6, 132.7, 133.1, 133.6, 135.5, 136.1, 164.9.
3g: Mp 136-138 °C. IR (KBr): 3342, 1656, 1604 cm^-1. ¹H NMR (CDCl₃): δ = 1.29-1.88 (m, 12 H), 2.31-2.58 (m, 3 H), 4.36 (br s, 1 H), 6.71-7.39 (m, 4 H). ¹³C NMR (CDCl₃): δ = 23.5, 24.1, 24.4, 28.9, 33.4, 38.5, 39.4, 54.4, 67.3, 118.6, 119.5, 126.9, 132.3, 139.3, 143.3, 178.4.
3h: Mp 137-139 °C. IR (KBr): 3321, 1654, 1600 cm^-1. ¹H NMR (CDCl₃): δ = 1.88-2.58 (m, 16 H), 2.46-2.79 (m, 3 H), 4.55 (br s, 1 H), 6.65-7.36 (m, 4 H). ¹³C NMR (CDCl₃): δ = 21.5, 21.7, 23.3, 24.5, 25.4, 33.4, 34.4, 39.3, 40.5, 52.4, 63.2, 121.1, 121.4, 126.3, 129.7, 138.2, 142.4, 178.8.