Organic Syntheses, Vol. 79, pp. 125-129
CAMPHORQUINONE AND CAMPHORQUINONE MONOXIME
[Bicyclo[2.2.1]heptane-2,3-dione, 1,7,7-trimethyl-, (1R)- and Bicyclo[2.2.1]heptan-2-one, 1,7,7-trimethyl-3-oxime, (1R)-]
Submitted by James D. White, Duncan J. Wardrop, and Kurt F. Sundermann1.
Checked by Kenji Koga, Kei Manabe, Christopher E. Neipp, and Stephen F. Martin.
1. Procedure
Caution! Parts A and B should be carried out in a well ventilated hood since toxic selenium dioxide is used.
A. (1R,4S)-(−)-Camphorquinone (Note 1). A 125-mL, three-necked, round-bottomed flask, equipped for mechanical stirring and outfitted with a reflux condenser, is charged with 20.0 g (0.13 mol) of (+)-camphor (1) (Note 2), 8.0 g (0.07 mol) of selenium dioxide (Caution! Selenium dioxide is toxic) (Note 3), and 14.0 mL of reagent grade acetic anhydride (Note 4). The green mixture is stirred at reflux for 1 hr, cooled to ambient temperature, and an additional 8.0 g (0.07 mol) of selenium dioxide is added. The mixture is again heated to reflux, and two further batches of 8.0 g (0.07 mol) of selenium dioxide are added at 2.5-hr and 6-hr intervals. After the reaction is heated at reflux for an additional 8 hr, during which time precipitation of selenium metal is observed, it is cooled to ambient temperature and transferred to a 125-mL beaker with the aid of 50 mL of ethyl acetate. The black precipitate is removed by filtration, and the filtrate is diluted with 100 mL of toluene (Note 5). Concentration of the filtrate by rotary evaporation gives crude 2 as an orange solid. This is dissolved in 200 mL of ethyl acetate, and the solution is filtered by vacuum filtration through Celite. The filtrate is transferred to a 1-L separatory funnel and is washed successively with 200 mL of 10% aqueous sodium hydroxide solution and 100 mL of saturated aqueous sodium chloride solution. The organic solution is dried over magnesium sulfate, filtered, and concentrated by rotary evaporation to afford 20.89 g of crude (1R,4S)-(−)-camphorquinone (2) as yellow crystals, mp 198-199°C (Notes 6 and 7). This material is suitable for the next reaction without purification.
B. (1R,4S)-(−)-Camphorquinone monoxime. A 500-mL, single-necked, round-bottomed flask equipped with a magnetic stirring bar is charged with 10.0 g (0.060 mol) of crude (1R)-(−)-camphorquinone (2), 240 mL of ethanol, 40 mL of pyridine (Note 8) and 5.44 g (0.078 mol) of hydroxylamine hydrochloride (NH2OH·HCl) (Note 9). The solution is stirred for 20 min, and the ethanol is removed by rotary evaporation at 40°C. The resulting oil is diluted with 100 mL of hexane and 100 mL of ethyl acetate, and the solution is transferred to a 1-L separatory funnel. The organic phase is separated and washed successively with 125 mL of 5% hydrochloric acid solution, 300 mL of water, and 300 mL of saturated aqueous sodium chloride solution. The organic solution is dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. The residue is taken up in 65 mL of heptane and heated to reflux. After reflux is maintained for 2 min, the mixture is allowed to cool to room temperature. The solid is collected by vacuum filtration, and the filter cake is dried under high vacuum to provide 8.63 g (79%) of (1R)-(−)-camphorquinone oxime (3) as an off-white solid (Note 10). This is a mixture of syn- and anti-oxime isomers, mp 148-151°C [α]D22 +184° (CH2Cl2, c 3.5) (Note 11).
2. Notes
1. Camphorquinone is available in racemic and both enantiomeric forms from Aldrich Chemical Company, Inc.
2. (+)-Camphor was purchased from Aldrich Chemical Company, Inc. and was used without purification.
3. Selenium dioxide was purchased from Aldrich Chemical Company, Inc.
4. Reagent grade acetic anhydride was purchased from Fischer Scientific.
5. Addition of toluene at this stage aids the removal of traces of acetic acid.
6. The crude product (2) is of sufficient purity for the next step even if trace amounts of acetic acid and selenium dioxide remain. The material can be purified by crystallization from a mixture of hexane and 2-propanol to provide a product with mp 198-199°C (lit. mp 199°C)2 and [α]D22 −103° (toluene, c 2.0).
7. The spectral properties of (1R,4S)-(−)-camphorquinone (2) are as follows: 1H NMR (300 MHz, CDCl3) δ: 0.92 (s, 3 H), 1.03 (s, 3 H), 1.08 (s, 3 H), 1.52-1.68 (m, 2 H), 1.79-1.94 (m, 1 H), 2.06-2.22 (m, 1 H), 2.62 (d, 1 H, J = 5.4); 13C NMR (75 MHz, CDCl3) δ: 8.9, 17.6, 21.3, 22.4, 30.1, 42.8, 58.1, 58.8, 203.0, 205.0; IR (film) cm1: 1767, 1746, 994
8. Reagent grade pyridine was purchased from Fischer Scientific Company.
9. Analytical reagent grade hydroxylamine hydrochloride was purchased from Mallinckrodt Inc.
10. The camphorquinone monoxime 3 is not completely soluble in 65 mL of boiling heptane, but it is nevertheless obtained in pure form after this step.
11. The spectral properties of syn- and anti-(1R,4S)-(−)-camphorquinone monoxime (3) are as follows: 1H NMR (300 MHz, CDCl3) δ: 0.84 (s, 2.6 H), 0.88 (s, 0.4 H), 0.96 (s, 3 H), 0.97 (s, 0.4 H), 0.98 (s, 2.6 H), 1.47-2.12 (comp, 5 H), 2.68 (d, 0.1 H, J = 4.1), 3.23 (d, 0.9 H, J = 4.6); 13C NMR (75 MHz, CDCl3) δ (major isomer): 8.9, 17.6, 20.6, 23.7, 30.6, 44.8, 46.6, 58.5, 159.6, 204.3; IR (CHCl3) cm1: 3262, 2963, 2878, 1748, 1654; mass spectrum (CI) m/z 182.1179 [C10H15NO2 (M+1) requires 182.1181], 182 (base), 136.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
(−)-Camphorquinone (2) is most conveniently prepared from (1R,4R)-(+)-camphor (1) by the method of Rupe,3 and is converted to a mixture of syn and anti monoximes 3 by the method of Cherry, et al.2 The oxime 3 has also been obtained by nitrosation of camphor.4
This preparation is referenced from:
References and Notes
  1. Department of Chemistry, Oregon State University, Corvallis, OR 97331-4003.
  2. Cherry, P. C.; Cottrell, W. R. T.; Meakins, G. D.; Richards, E. E J. Chem. Soc. (C) 1968, 459.
  3. Rupe, H.; Tommasi di Vignano, A. Helv. Chim. Acta 1937, 20, 1078.
  4. Forster, M. O.; Rao, K. S. N. J. Chem. Soc. 1926, 2670.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

(1R,4S)-(−)-Camphorquinone: Bicyclo[2.2.1]heptane-2,3-dione, 1,7,7-trimethyl-, (1R)-; (10334-26-6)

(1R,4S)-(−)-Camphorquinone monoxime: 2,3-Bornanedione, 3-oxime (9); Bicyclo[2.2.1]heptan-2-one, 1,7,7-trimethyl-, 3-oxime, (1R)- (12); (663-17-2)

(+)-Camphor: Camphor, (1R,4R)-(+)- (8); Bicyclo[2.2.1]heptan-2-one, 1,7,7-trimethyl-, (1R)-; (464-49-3)

Selenium dioxide: Selenium oxide (8,9); (7446-08-4)

Acetic anhydride (8); Acetic acid, anhydride (9); (108-24-7)

Hydroxylamine hydrochloride (8); Hydroxylamine, hydrochloride (9); (5470-11-1)