An Improved, Fully Heterogeneous, Diastereoselective Synthesis of (Z)-α-Bromonitroalkenes

Abstract

α-Bromonitroalkenes are both key starting materials for the preparation of complex structures and possess antimicrobial activity. In this context, we disclose a simple, fully heterogeneous synthetic approach for their preparation in good overall yields.

Key words

Henry reaction - dehydration - diastereoselectivity - α-bromo­nitroalkanes - heterogeneous catalysis

• References and Notes

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• 9 Usually, the dehydration of bromonitroalkanols is performed under basic conditions, see ref. 6.
• 10 Typical Procedure for the Synthesis of Compounds 5 The catalyst (0.56 g, 0.3 mmol) was slowly added at r.t. to a mechanically stirred mixture of the bromonitromethane (6, 1 mmol, 0.155 g, pure 90%) and the requisite aldehyde 1 (1 mmol), and the reaction was stirred for the appropriate time (see Table). The mixture was then treated with EtOAc (5 mL), and the catalyst was filtered off and washed with additional EtOAc (10 mL). The solution was concentrated under reduced pressure to a volume of 3 mL and then treated with Ac₂O (306 mg, 3 mmol) and Amberlyst 15 (0.5 g) and stirred, at r.t., for an additional 1.5 h. Finally, the Amberlyst 15 was removed by filtration, washing with EtOAc (7 mL), and the solution was concentrated under vacuum giving the crude product 5 which was purified by flash chromatography (hexane–EtOAc = 9:1). (Z)-1-Bromo-1-nitrohept-1-ene (5a) Light yellow oil. IR (neat): ν = 3045, 1551, 1325, 1261, 942, 722 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.91 (t, 3 H, J = 6.8 Hz), 1.30–1.40 (m, 4 H), 1.51–1.61 (m, 2 H), 2.37 (q, 2 H, J = 7.3 Hz), 7.67 (t, 1 H, J = 7.3 Hz). ¹³C NMR (100MHz, CDCl₃): δ = 14.1, 22.5, 27.3, 31.3, 31.6, 131.2, 141.6. MS (EI, 70 eV): m/z (%) = 165, 142, 119, 95, 69, 55, 41 (100), 39, 30. Anal. Calcd for C₇H₁₂BrNO₂ (222.08): C, 37.86; H, 5.45; N, 6.31. Found: C, 37.91; H, 5.49; N, 6.28. (Z)-1-Bromo-1-nitronon-1-ene (5b) Light yellow oil. IR (neat): ν = 3040, 1542, 1321, 1254, 960, 768 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.89 (t, 3 H, J = 6.8 Hz), 1.23–1.41 (m, 8 H), 1.50–1.61 (m, 2 H), 2.37 (q, 2 H, J = 7.3 Hz), 7.66 (t, 1 H, J = 7.3 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 14.3, 22.8, 27.6, 29.1, 29.4, 31.3, 31.9, 131.2, 141.6. MS (EI, 70 eV): m/z (%) = 234, 121, 93, 81, 67, 55, 43 (100), 41, 39, 29. Anal. Calcd for C₉H₁₆BrNO₂ (250.13): C, 43.22; H, 6.45; N, 5.60. Found: C, 43.27; H, 6.49; N, 5.58. (Z)-(2-Bromo-2-nitrovinyl)cyclohexane (5c) Light yellow oil. IR (neat): ν = 3030, 1539, 1320, 971, 960, 761 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.18–1.44 (m, 6 H), 1.65–1.84 (m, 4 H), 2.39–2.53 (m, 1 H), 7.48 (d, 1 H, J = 9.8 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 25.3, 25.7, 30.8, 40.8, 129.7, 145.3. MS (EI, 70 eV): m/z (%) = 218, 216, 137, 119, 97, 91, 81, 79, 71, 69, 55 (100), 41, 39. Anal. Calcd for C₈H₁₂BrNO₂ (234.09): C, 41.05; H, 5.17; N, 5.98. Found: C, 41.09; H, 5.21; N, 5.96. (Z)-(4-Bromo-4-nitrobut-3-enyl)benzene (5d) Light yellow oil. IR (neat): ν = 3035, 1618, 1525, 1331, 937, 750, 724, 698 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.71 (q, 2 H, J = 7.7 Hz), 2.88 (t, 2 H, J = 7.7 Hz), 7.17–7.36 (m, 5 H), 7.67 (t, 1 H, J = 7.7 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 33.0, 33.6, 127.0, 128.5, 129.0, 131.8, 139.7, 140.2. MS (EI, 70 eV): m/z (%) = 240, 238, 129, 91 (100), 65. Anal. Calcd for C₁₀H₁₀BrNO₂ (256.10): C, 46.90; H, 3.94; N, 5.47. Found: C, 46.88; H, 3.97; N, 5.44. (Z)-Ethyl 3-Bromo-3-nitroacrylate (5e) Light yellow oil. IR (neat): ν = 1733, 1622, 1552, 1323 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (t, 3 H, J = 7.3 Hz), 4.34 (q, 2 H, J = 7.3 Hz), 7.74 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 62.8, 125.8, 139.3, 162.2. MS (EI, 70 eV): m/z (%) = 180, 178, 166, 164, 151, 149, 133, 131, 106, 104, 69, 53, 29 (100). Anal. Calcd for C₅H₆BrNO₄ (224.01): C, 26.81; H, 2.70; N, 6.25. Found: C, 26.86; H, 2.72; N, 6.22. (Z)-1-(2-Bromo-2-nitrovinyl)-4-tert-butylbenzene (5f) Yellow solid, mp 50–52 °C. IR (neat): ν = 3030, 1599, 1530, 1325, 953, 834, 762 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.35 (s, 9 H), 7.51 (d, 2 H, J = 8.5 Hz), 7.86 (d, 2 H, J = 8.5 Hz), 8.64 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 31.3, 35.4, 126.3, 127.3, 127.5, 131.3, 136.7, 156.3. MS (EI, 70 eV): m/z (%) = 285, 283, 270, 268, 222, 220, 143 (100), 128, 115, 57. Anal. Calcd for C₁₂H₁₄BrNO₂ (284.15): C, 50.72; H, 4.97; N, 4.93. Found: C, 50.76; H, 5.00; N, 4.90. (Z)-1-(2-Bromo-2-nitrovinyl)-3-methoxybenzene (5g) Yellow solid, mp 68–70 °C. IR (neat): ν = 3070, 3029, 1607, 1553, 1331, 1176, 897, 743 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.86 (s, 3 H), 7.07 (d, 1 H, J = 7.7 Hz), 7.38–7.46 (m, 3 H), 8.61 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 55.6, 115.8, 118.0, 124.0, 128.5, 130.2, 131.5, 136.6, 159.9. MS (EI, 70 eV): m/z (%) = 259, 257, 212, 210, 150, 148, 132 (100), 102, 89, 77, 63. Anal. Calcd for C₉H₈BrNO₃ (258.07): C, 41.89; H, 3.12; N, 5.43. Found: C, 41.93; H, 3.10; N, 5.40. (Z)-1-(2-Bromo-2-nitrovinyl)-4-methoxybenzene (5h) Yellow solid, mp 59–61 °C. IR (neat): ν = 3041, 1520, 1310, 1261, 1181, 957, 825 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.88 (s, 3 H), 7.00 (d, 2 H, J = 8.5 Hz), 7.92 (d, 2 H, J = 8.5 Hz), 8.63 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 55.8, 114.8, 122.6, 125.6, 133.7, 136.6, 163.0. MS (EI, 70 eV): m/z (%) = 259, 257, 212, 210, 132 (100), 117, 89, 63. Anal. Calcd for C₉H₈BrNO₃ (258.07): C, 41.89; H, 3.12; N, 5.43. Found: C, 41.93; H, 3.09; N, 5.45. (Z)-1-Bromo-2-(2-bromo-2-nitrovinyl)benzene (5i) Yellow waxy solid. IR (neat): ν = 3078, 3035, 1606, 1582, 1532, 1300, 898, 764, 733, 703 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.35 (t, 1 H, J = 7.7 Hz), 7.44 (t, 1 H, J = 7.7 Hz), 7.69 (d, 1 H, J = 7.7 Hz), 7.86 (d, 1 H, J = 7.7 Hz), 8.77 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 125.7, 127.7, 130.6, 131.3, 131.6, 132.5, 133.5, 136.2. MS (EI, 70 eV): m/z (%) = 309, 307, 305, 262, 260, 258, 228, 226, 198, 196, 182, 180 (100), 147, 101, 75, 50. Anal. Calcd for C₈H₅Br₂NO₂ (306.94): C, 31.30; H, 1.64; N, 4.56. Found: C, 31.33; H, 1.65; N, 4.54. (Z)-5-(2-Bromo-2-nitrovinyl)-1,2,3-trimethoxybenzene (5j) Orange solid, mp 113–115 °C. IR (neat): ν = 3075, 3035, 1603, 1577, 1522, 1333, 1246, 1125, 824, 618 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.91 (s, 6 H), 3.93 (s, 3 H), 7.19 (s, 2 H), 8.59 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 56.4, 56.5, 61.3, 105.9, 108.9, 125.2, 127.1, 131.9, 136.7, 141.8, 153.4. MS (EI, 70 eV): m/z (%) = 319, 317, 272, 270, 257, 255, 192, 177 (100), 149, 134, 119, 63. Anal. Calcd for C₁₁H₁₂BrNO₅ (318.12): C, 41.53; H, 3.80; N, 4.40. Found: C, 41.57; H, 3.82; N, 4.38. (Z)-2-Bromo-5-(2-bromo-2-nitrovinyl)furan (5k) Yellow solid, mp 87–89 °C. IR (neat): ν = 3134, 3036, 1618, 1537, 1505, 1348, 1292, 1025, 948, 818, 786, 645 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 6.61 (d, 1 H, J = 3.4 Hz), 7.37 (d, 1 H, J = 3.4 Hz), 8.50 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 115.8, 122.3, 124.0, 125.1, 129.6, 148.6. MS (EI, 70 eV): m/z (%) = 299, 297, 295, 225, 223, 221, 135, 133, 79, 63 (100). Anal. Calcd for C₆H₃Br₂NO₃ (296.90): C, 24.27; H, 1.02; N, 4.72. Found: C, 24.30; H, 1.03; N, 4.69.