Practical and User-Friendly Procedure for Michael Reactions of α-Nitro­ketones in Water

Abstract

A variety of α,β-unsaturated carbonyl derivatives gave selective Michael additions with several α-nitrocycloalkanones in water, at room temperature without any added catalyst, or in very dilute, aqueous solutions of potassium carbonate. Both preparative methods constitute new, environmentally benign and more efficient alternatives to previous procedures.

Michael additions - carbanions - nucleophillic additions - nitroketones - organic reactions in water

References

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These starting materials were prepared in two steps, by transformation of commercially available cycloalkanones into the enol acetates and subsequent treatment of the latter compounds with acetyl nitrate.
Representative Procedure: To a solution of cyclo-heptanone (10 g, 90 mmol) in isopropenyl acetate (85 mL) was added p-toluenesulfonic acid (2.9 g, 15 mmol). The reacting mixture was refluxed for 24 h in an oil bath at 100 °C, and then it was cooled and diluted with Et₂O
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1 H, H-3), 2.20-2.00 (m, 2 H, H-5,3), 2.00-1.75 (m, 2 H,
H-6,4), 1.75-1.50 (m, 2 H, H-6,4), 1.50-1.25 (m, 1 H, H-5). ¹³C NMR (63 MHz, CDCl₃): δ = 201.7 (C-1), 94.1 (C-2), 41.7 (C-7), 29.1 (C-5), 29.0 (C-3), 26.6 (C-4), 24.2 (C-6). Anal. Calcd. for C₇H₁₁NO₃ (M = 157): C, 53.50; H, 7.00; N, 8.92. Found: C, 53.37; H, 7.06; N, 8.85.

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The rationalization given in this reference for the formation of 4 differs from the one proposed in Scheme [1] .

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<A NAME="RD17803ST-23">23</A>

Representative Procedure: To a vigorously stirred dispersion of α-nitrocycloheptanone 2a (150 mg, 0.96 mmol) in H₂O (5 mL) was added acrolein (2.4 mmol, 2.5 equiv). The mixture was stirred at r.t. for 8 h, and the aqueous phase was then extracted with Et₂O (3 × 10 mL), which was dried (Na₂SO₄) and evaporated, yielding 172 mg (85%) of 3-(1′-nitro-2′-oxocycloheptyl)-propanal (3a), as a pale yellow, viscous liquid. IR (NaCl): 1721 (C=O), 1542 and 1347 (NO₂) cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 9.77 (s, 1 H, CHO), 2.80-1.40 (m, 14 H). ¹³C NMR (63 MHz, CDCl₃): δ = 202.5 (C-2′), 199.7 (C-1), 98.4 (C-1′), 41.2 (C-3′), 38.3 (C-2), 35.1 (C-5′), 29.3 (C-7′), 28.6 (C-6′), 25.5 (C-4′), 24.4 (C-2). Anal. Calcd for C₁₀H₁₅NO₄: C, 56.33; H, 7.09; N, 6.57. Found: C, 56.59; H, 7.29; N, 6.49.

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<A NAME="RD17803ST-26">26</A>

For a similar effect of K₂CO₃ in the Michael reactions of 1,3-diones, see ref. [21]