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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18

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
(20 mL). The solution was washed with sat. aq NaHCO₃ (2 × 30 mL) and brine (2 × 30 mL). The organic layer was dried (Na₂SO₄) and evaporated, yielding 1-cycloheptenyl acetate (14.08 g, 100%), as a dark brown oil. To a solution of this compound in CH₂Cl₂ (30 mL) at 0 °C was successively added acetic anhydride (28.26 mL, 30.55 g, 295.7 mmol) and 96% sulfuric acid (0.5 mL). A mixture of glacial acetic acid (2.25 mL, 2.39 g, 40.8 mmol) and 65% nitric acid (6.75 mL) was then added dropwise. After stirring for an additional time of 3 h, the reacting mixture was diluted with CH₂Cl₂ (30 mL) and washed with brine (2 × 20 mL), and sat. aq NaHCO₃ (3 × 20 mL, until no effervescence was observed). The organic layer was dried (Na₂SO₄) and evaporated and the residue was chromato-graphed on silica gel, eluting with 10:1 petroleum ether-ethyl acetate, yielding 7.482 g (54%) of compound 2a, as a pale yellow viscous oil. IR (NaCl): 1721 (C=O), 1158 and 1375 (NO₂) cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 5.34 (dd, 1 H, J = 9.5 and 3.9 Hz, H-2), 2.80-2.50 (m, 2 H, H-7), 2.40-2.20 (m,
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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21b

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

22 For a similar effect with 1,3-diones, see: Crispin DJ. Vanstone AE. Whitehurst JS. J. Chem. Soc. C  1970,  10 

23

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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26

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