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Synlett 2004(13): 2315-2318  
DOI: 10.1055/s-2004-832815
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Practical and User-Friendly Method for the Selenium-Free One-Step Preparation of 1,2-Diketones and their Monoxime Analogs

Georg Rüedi*a, Matthias A. Oberlia, Matthias Nagelb, Christophe Weymutha, Hans-Jürgen Hansena
a Organisch-chemisches Institut, Universität Zürich, Winterthurerstrasse190, 8057 Zürich, Switzerland
Fax: +41(1)6356853; e-Mail: georg@access.unizh.ch;
b Swiss Federal Laboratories for Materials Testing and Research (EMPA), Überlandstrasse 138, 8600 Dübendorf, Switzerland
Further Information

Publication History

Received 18 June 2004
Publication Date:
24 September 2004 (online)

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Abstract

Treatment of α-methylene ketones with excess sodium nitrite and aqueous HCl in THF at reduced temperatures provides an effective tool for the preparation of a variety of 1,2-diketones. The diastereoselective synthesis of the corresponding (Z)-1,2-dione monoximes could be accomplished under similar conditions, but by using only one equivalent of nitrosating reagent.

Key words

1,2-diketones - 1,2-dione monoximes - nitrosation - α-oximation - oxidations

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The 1H NMR of 2 showed a significantly low field shifted singlet at δ = 8.53 ppm accounting for an OH group being part of a hydrogen bridge.

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MS analysis provided evidence for the formation of a minor amount of a dehydrogenated form of 2, that was purified by silica gel chromatography, characterized and proved to be 2-nitroso-cyclododec-2-enone (1% yield), colorless oil. 1H NMR (300 MHz, CDCl3): δ = 6.91 (t, 3 J = 7.7 Hz, 1 H), 2.74 (t, 3 J = 6.7 Hz, 2 H), 2.46 (dt, 3 J = 7.7 Hz, 3 J = 6.2 Hz, 2 H), 1.80-1.66 (m, 2 H), 1.46 (quint., 3 J = 6.2 Hz, 2 H), 1.34-1.23 (m, 10 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 198.23 (s, C1), 140.99 (d, C3), 133.57 (s, C2), 37.53 (t), 29.07 (t), 26.55 (t), 25.66 (t), 24.79 (t), 24.75 (2 C, t), 24.72 (t), 23.95 (t)ppm. MS (EI): m/z (%) for C12H19NO2 (209.29) = 209 (19) [M - NO]+ , 161 (16), 149 (10), 143 (23), 132 (27), 111 (32), 98 (100), 84 (67), 55 (71).

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In a control experiment we could show that diketone 3 did not react further to give the corresponding 1,2,3-trione, even if large excess of sodium nitrite in combination with longer reaction times was used.

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General Procedure for the Prearation of 1,2-Diketones and 1,2-Dione Monoximes.
A suspension of the starting ketone (50 mmol) and NaNO2 (10.35 g, 150 mmol) in THF (100 mL) was cooled to 0 °C. To this mixture, concd HCl (65 mL) was added in such a way that the temperature did not exceed 10 °C. In order to avoid the evolution of nitrous gases the acid was added via cannula that was immerged into the reaction mixture. After the addition the cooling bath was removed and the suspension turned dark yellow. The progress of the reaction was monitored by GC. After the starting material had vanished (0.1-12 h) the reaction mixture containing the crude 1,2-diketone was poured into a separatory funnel containing crushed ice (200 g) and Et2O (100 mL). The organic layer was separated, and the aqueous phase extracted with Et2O (3 × 100 mL). The combined organic layers were washed with a sat. aq solution of NaHCO3 (100 mL) and with brine (100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by filtration over a pad of silica gel (5:1) using hexane-EtOAc (50:1) as eluent. The corresponding 1,2-dione monoximes were prepared accordingly by using only 3.45 g (50 mmol) of NaNO2 and 25 mL of concd HCl. The crude product was purified either by filtration over a pad of silica gel (5:1) using hexane-EtOAc (50:1) as eluent or by crystallization from hexane-EtOAc.

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All new compounds were fully characterized. Selected data for novel compounds:
3-Methylcyclododecane-1,2-dione (6f): yellow oil (1.42 g). 1H NMR (300 MHz, CDCl3): δ = 3.52 (qdd, 3 J = 7.0 Hz, 3 J = 6.9 Hz, 3 J = 3.5 Hz, 1 H, H-C3), 3.36-3.27 (m, 1 H), 2.26-2.17 (m, 1 H), 1.82-1.68 (m, 3 H), 1.38-1.17 (m, 13 H), 1.10 (d, 3 J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.07 (s, C2), 201.93 (s, C1), 38.34 (d, C3), 36.47 (t, C12), 29.86 (t), 26.34 (t), 26.17 (t), 24.95 (t), 23.79 (t), 23.70 (t), 22.09 (t), 14.45 (q, CH3) ppm. MS (EI): m/z (%) C13H22O2 (210.32) = 210 (7) [M+ ], 192 (1), 167 (3), 153 (6), 139 (8), 125 (22), 112 (29), 98 (37), 83 (24), 69 (51), 55 (100). Anal. Calcd for C13H22O2 (210.32): C, 74.24; H, 10.54. Found: C, 74.44; H, 10.60.
( Z )-3-Methylcyclododecane-1,2-dione-1-oxime (5f): colorless crystals (0.99 g); mp 97-98 °C (from hexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = ca. 8 (s, 1 H, NOH), 3.62 (qdd, 3 J = 7.0 Hz, 3 J = 6.9 Hz, 3 J = 3.6 Hz, 1 H, H-C12), 2.89-2.80 (m, 1 H), 2.65-2.57 (m, 1 H), 1.84-1.76 (m, 1 H), 1.66-1.42 (m, 3 H), 1.37-1.16 (m, 12 H), 1.09 (d, 3 J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 203.15 (s, C1), 160.06 (s, C2), 39.64 (d, C12), 31.38 (t, C3), 26.09 (t, 2 C), 25.04 (t), 23.42 (t), 22.87 (t), 22.65 (t), 21.89 (t), 21.19 (t), 15.12 (q, CH3) ppm. MS (EI): m/z (%) C13H23NO2 (225.32) = 225 (4) [M+ ], 208 (26), 197 (5), 180 (42), 168 (11), 138 (18), 124 (26), 110 (28), 96 (34), 82 (37), 69 (45), 55 (100). Anal. Calcd for C13H23NO2 (225.33): C, 69.29; H, 10.29; N, 6.22. Found: C, 69.18; H, 10.19; N, 6.11.
3-Methoxycyclododecane-1,2-dione (6g): yellow oil (1.23 g). 1H NMR (300 MHz, CDCl3): δ = 4.85 (t, 3 J = 4.4 Hz, 1 H, H-C3), 3.38 (s, 3 H, OCH3), 2.23-2.14 (m, 1 H), 1.90-1.83 (m, 2 H), 1.73-1.66 (m, 2 H), 1.53-1.49 (m, 1 H), 1.39-1.02 (m, 12 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 202.10 (s), 199.00 (s), 81.14 (d, C3), 57.61 (q, OCH3), 36.71 (t, C12), 27.30 (t), 26.21 (t), 26.17 (t), 24.33 (t), 23.29 (t), 22.03 (t), 21.83 (t), 19.48 (t) ppm. MS (EI): m/z (%) C13H22O2 (210.32) = 226 (1) [M+ ], 198 (8), 148 (5), 138 (8), 127 (6), 109 (13), 96 (19), 82 (43), 71 (100), 55 (34). Anal. Calcd for C13H22O3 (226.32): C, 68.99; H, 9.80. Found: C, 69.12; H, 9.85.
( Z )-3-Methoxycyclododecane-1,2-dione-1-oxime (5g): colorless crystals (1.86 g); mp 100-102 °C (from hexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 7.50 (s, 1 H, NOH), 4.88-4.86 (m, 1 H, H-C12), 3.37 (s, 3 H, OCH3), 2.94-2.84 (m, 1 H), 2.65-2.58 (m, 1 H), 1.97-1.86 (m, 2 H), 1.55-1.37 (m, 2 H), 1.36-1.02 (m, 12 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 198.16 [s, C(1)], 159.63 [s, C(2)], 82.52 [d, C(12)], 57.46 (q, OCH3), 29.03 (t), 26.24 (t), 26.16 (t), 24.02 (t), 22.81 (t), 22.50 (t), 21.91 (t), 21.78 (t), 18.80 (t)ppm. MS (EI): m/z (%) C13H23NO2 (225.33) = 241 (2) [M+ ], 224 (58), 196 (95), 182 (17), 166 (14), 120 (23), 110 (21), 96 (27), 71 (100), 55 (52). Anal. Calcd for C13H23NO3 (241.33): C, 64.70; H, 9.61; N, 5.80. Found: C, 64.83; H, 9.70; N, 5.88.

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(+)- trans -2-(2,2,3-Trimethylcyclopentyl)-1-phenyl-ethanedione (13): bright yellow oil; [α]D 23 +39.2 (c 1.6, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 8.03 (dd, 3 J = 8.2 Hz, 4 J = 1.4 Hz, 2 H), 7.64-7.59 (m, 1 H), 7.52-7.47 (m, 2 H), 3.61 (dd, 3 J = 8.3, 6.4 Hz, 1 H), 2.10-1.24 (m, 5 H), 0.97 (s, 3 H), 0.95 (s, 3 H), 0.87 (d, 3 J = 6.9 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 205.83 (s), 192.16 (s), 135.10 (s), 134.17 (d), 130.40 (d), 128.70 (d), 55.64 (d), 45.75 (s), 44.27 (d), 31.74 (t), 24.92 (q), 24.81 (t), 24.22 (q), 14.44 (q) ppm. MS (EI): m/z (%) C16H20O2 (244.33) = 244 (3) [M+ ], 139 (59) [M - COPh]+ , 111 (97), 105 (82) [COPh+ ], 77 (75), 69 (100), 55 (94).

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Several reactions were conducted on a 20 g scale.