Org. Synth. 1985, 63, 188
DOI: 10.15227/orgsyn.063.0188
HEXAHYDRO-2-(1H)-AZOCINONE
[2(1H)-Azocinone, hexahydro-]
Submitted by George A. Olah and Alexander P. Fung
1.
Checked by David Varie and Edwin Vedejs.
Checked by Scott Thompson and Clayton H. Heathcock.
1. Procedure
A
100-mL, three-necked flask is equipped with a
magnetic stirring bar, a
pressure-equalizing dropping funnel, and a
reflux condenser connected to a nitrogen flow line. The system is dried with a heat gun while it is flushed with dry
nitrogen. The reaction vessel is then cooled in a
water bath while a light positive pressure of
nitrogen is maintained. The flask is charged with
hydroxylamine-O-sulfonic acid2 (8.48 g, 0.075 mol) (Note 1) and
95–97% formic acid (45 mL) (Note 2). A solution of
cycloheptanone (5.61 g, 0.05 mol) (Note 3) in
15 mL of 95–97% formic acid is added with stirring over a 3-min period. After addition is complete, the reaction mixture is heated under reflux for 5 hr and then cooled to room temperature. The reaction mixture is quenched with 75 mL of ice–water. The aqueous solution is slowly neutralized to pH ~7 with
6 N sodium hydroxide (Note 4) and extracted with three
100-mL portions of chloroform. The combined organic layers are dried with anhydrous
magnesium sulfate. After removal of the solvent on a
rotary evaporator, the product
hexahydroazocinone is purified by distillation to give
4.6 g (
72%), bp
94–96°C/0.2 mm, (short-path apparatus), lit
3 bp
133–135°C/4 mm (Note 5).
2. Notes
1.
The
hydroxylamine-O-sulfonic acid used by the submitters was purchased from Ventron Corporation and used directly. However, it can be readily prepared in the laboratory.
4,32.
Formic acid 95–97% was obtained from the Aldrich Chemical Company.
3.
Commercial
cycloheptanone (bp 179°C) obtained from MCB, Inc. was used directly.
4.
An external
ice–salt bath is used.
5.
The product exhibits the following spectra:
1H NMR (CDCl
3) δ: 1.6–1.8 (m, 6 H, CH
2), 2.40 (3 H, m), 2.57 (m, 2 H, CH
2CO), 3.31 (m, 2 H, CH
2-N), 7.16 (br, 1 H, NH); IR (cm
−1): 3270, 3200, 1650; GLC analysis: 20% SE-30, 60/80 on Chrom-W,
1/8-in × 20-ft column, 180°C: one peak.
3. Discussion
The procedure described here is a one-step conversion of
cycloheptanone into
hexahydro-2(1H)-azocinone. The method is general and is characterized by good yields, mild conditions, and easy preparation of the product in pure form from readily available starting materials. Several methods are described in the patent literature for simultaneous oximation of ketones and rearrangement of the corresponding oxime, including the use of hydroxylamine and
sulfuric acid,
5,6 or by employing primary nitroparaffins as a source of hydroxylamine.
7,8 The present method has been shown
9 to be applicable to a wide variety of lactams (C
5 ~ C
12). In the specific case of
hexahydroazocinone, the yield from
cycloheptanone (
60–63%) appears lowers than for the conventional two-step method,
10,11 but the latter requires isolation of the intermediate oxime.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
sulfuric acid (7664-93-9)
sodium hydroxide (1310-73-2)
chloroform (67-66-3)
formic acid (64-18-6)
nitrogen (7727-37-9)
magnesium sulfate (7487-88-9)
Cycloheptanone (502-42-1)
Hydroxylamine-O-sulfonic acid (2950-43-8)
hexahydroazocinone (673-66-5)
Hexahydro-2-(1H)-azocinone,
2(1H)-Azocinone, hexahydro-,
hexahydro-2(1H)-azocinone (673-66-5)
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