Org. Synth. 2002, 79, 125
DOI: 10.15227/orgsyn.079.0125
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. Sundermann
1
.
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]D
22 +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]D
22
−103° (toluene, c 2.0).
7.
The spectral properties of
(1R,4S)-(−)-camphorquinone
(
2) are as follows: 1H
NMR (300 MHz, CDCl
3) 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, CDCl
3)
δ: 8.9, 17.6, 21.3, 22.4,
30.1, 42.8, 58.1, 58.8, 203.0,
205.0
; IR (film) cm
−1:
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, CDCl
3) 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, CDCl
3) δ (major isomer): 8.9, 17.6,
20.6, 23.7, 30.6, 44.8, 46.6,
58.5, 159.6, 204.3
; IR (CHCl
3) cm
−1: 3262, 2963,
2878, 1748, 1654
; mass spectrum (CI) m/z 182.1179 [C
10H
15NO
2
(M+1) requires 182.1181], 182 (base), 136
.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
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:
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)
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