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Synlett 2003(14): 2159-2162  
DOI: 10.1055/s-2003-42096
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Sonia Mirandaa, Pilar López-Alvaradoa, Giorgio Giorgia, Jean Rodriguezb, Carmen Avendañoa, J. Carlos Menéndez*a
a Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
e-Mail: josecm@farm.ucm.es;
b Laboratoire RéSo, UMR-CNRS 6516 Réactivité en Synthèse Organique, Centre de St Jérôme, boîte D12, 13397 Marseille, cedex 20, France
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Publication History

Received 16 July 2003
Publication Date:
15 October 2003 (online)

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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.

Key words

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

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