A New Heterogeneous One-Pot Process for Both Nitroaldol (Henry) and Michael Reactions from Primary Haloalkanes via Nitroalkanes

Abstract

At room temperature, one equivalent of primary haloalkane and aldehyde, or conjugated enone, in the presence of IRA-402 nitrite and Amberlyst A-21, gave β-nitroalkanols or γ-nitro ketones, respectively, via a one-pot tandem S_N2-nitroaldol (Henry) or S_N2-Michael reactions.

Key words

one-pot process - haloalkanes - nitroalkanes - nitroaldol reaction - Henry reaction - Michael addition - heterogeneous process

References and Notes

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9

Preparation of Amberlite IRA-402 Nitrite: To a stirred solution of NaNO₂ (3 g) in H₂O (30 mL), Amberlite IRA-402 (Fluka; 3 g) was added and the heterogeneous mixture was heated at 40 °C for 30 min. Then, H₂O was separated from Amberlite by decantation, and the resin was washed with MeOH (2 × 15 mL) and with Et₂O (2 × 15 mL). Finally the exchanged resin was dried under vacuum.

10

General Procedure for the One-Pot Preparation of β-Nitroalkanols 6 and γ-Nitro Ketones 7: In a round-bottomed flask the resins IRA-402 nitrite (800 mg) and Amberlyst A-21 (600 mg), were added to a solution of DMF (2 mL), haloalkane 1 (1 mmol) and the appropriate electrophilic species 4 or 5 (1 mmol). The resulting mixture was stirred for the appropriate time (Table [1] ), then filtered and washed with Et₂O (20 mL). The organic layer was washed with cold H₂O (20 mL), dried (Na₂SO₄), filtered and evaporated yielding a crude product that was purified by flash chromatography (cyclohexane-EtOAc as eluent), giving the pure compound 6 or 7.

11

Selected Analytical Data for Compounds 6b,c and 7a,b: Compound 6b: yellow oil. IR (neat): 1456, 1916, 3354 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.86-0.92 (m, 3 H), 1.21-1.40 (m, 4 H), 1.60-1.93 (m, 3 H), 1.96-2.17 (m, 1 H), 2.32 (d, J = 8.1 Hz, 0.6 H), 2.45 (d, J = 4.3 Hz, 0.4 H), 2.65-2.80 (m, 1 H), 2.82-2.96 (m, 1 H), 3.82-3.94 (m, 0.6 H), 3.97-4.06 (m, 0.4 H), 4.40-4.49 (m, 1 H), 7.16-7.34 (m, 5 H). ¹³C NMR (100 MHz): δ = 13.9, 14.0, 22.3, 22.4, 27.9, 28.0, 28.3, 30.4, 31.8, 32.1, 35.0, 35.5, 71.4, 71.7, 92.5, 93.1, 126.5, 128.7, 128.8, 141.0. Anal. Calcd for C₁₄H₂₁NO₃: C, 66.91; H, 8.42; N, 5.57. Found: C, 67.24; H, 8.66; N, 5.38.
Compound 6c: yellow oil. IR (neat): 1730, 3404 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.96-1.04 (m, 3 H), 1.37-1.94 (m, 5 H), 2.03-2.21 (m, 1 H), 2.43 (d, J = 7.7 Hz, 0.5 H), 2.54 (d, J = 5.1 Hz, 0.5 H), 3.63-3.83 (m, 2.5 H), 3.88-3.96 (m, 0.5 H), 4.49-4.61 (m, 1 H), 7.68-7.74 (m, 2 H), 7.79-7.85 (m, 2 H). ¹³C NMR (100 MHz): δ = 10.0, 10.2, 25.2, 25.3, 26.6, 26.8, 27.7, 37.0, 37.1, 73.6, 73.8, 91.4, 91.9, 123.6, 132.1, 134.4, 168.6. Anal. Calcd for C₁₅H₁₈N₂O₅: C, 58.82; H, 5.92; N, 9.15. Found: C, 59.14; H, 6.18; N, 8.89.
Compound 7a: yellow oil. IR (neat): 1442, 1577, 1732 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.84-0.92 (m, 3 H), 1.23-1.40 (m, 4 H), 1.68-2.20 (m, 4 H), 2.25 (s, 3 H), 2.45-2.53 (m, 2 H), 4.43-4.52 (m, 1 H). ¹³C NMR (100 MHz): δ = 13.9, 22.2, 27.5, 28.0, 30.2, 33.8, 39.1, 88.1, 206.7. EI-MS (70 eV): m/z = 187, 157, 141, 123, 97, 83, 71, 55, 43 (100). Anal. Calcd for C₉H₁₇NO₃: C, 57.73; H, 9.15; N, 7.48. Found: C, 57.44; H, 8.91; N, 7.70.
Compound 7b: yellow oil. IR (neat): 1168, 1364, 1736 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.58-1.67 (m, 2 H), 1.72-1.81 (m, 1 H), 1.96-2.11 (m, 3 H), 2.02 (s, 3 H), 2.12 (s, 3 H), 2.43-2.52 (m, 2 H), 3.96-4.10 (m, 2 H), 4.47-4.56 (m, 1 H). ¹³C NMR (100 MHz): δ = 21.1, 25.2, 27.6, 30.3, 30.7, 39.1, 63.4, 87.6, 171.2, 206.6. EI-MS (70 eV): m/z = 43 (100), 81, 125, 141, 185, 231. Anal. Calcd for C₁₀H₁₇NO₅: C, 51.94; H, 7.41; N, 6.06. Found: C, 52.23; H, 7.61; N, 5.88.