New odorless protocols for the Swern and Corey-Kim oxidations

Article abstract of DOI:10.1016/S0040-4039(02)00968-1

New odorless protocols for the Swern oxidation as well as the Corey-Kim oxidation using dodecyl methyl sulfoxide (1) or dodecyl methyl sulfide (3) are described.

Full text of DOI:10.1016/S0040-4039(02)00968-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5177–5179
New odorless protocols for the Swern and Corey–Kim oxidations
Kiyoharu Nishide, Shin-ichi Ohsugi, Masato Fudesaka, Sumiaki Kodama and Manabu Node*
Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
Received 7 February 2002; revised 26 April 2002; accepted 17 May 2002
Abstract—New odorless protocols for the Swern oxidation as well as the Corey–Kim oxidation using dodecyl methyl sulfoxide (1)
or dodecyl methyl sulfide (3) are described. © 2002 Elsevier Science Ltd. All rights reserved.
The Swern oxidation [dimethyl sulfoxide (DMSO)–oxa-
lyl chloride]1 is the most commonly used of several
activated DMSO methods2 for oxidation of primary or
secondary alcohols to aldehydes or ketones. Among its
many advantages are mild conditions, stability of acid
sensitive functional groups, no epimerization of the
a-carbon of the carbonyl group, easy work-up, gaseous
byproducts (carbon dioxide and carbon monoxide), and
rapid reaction rate.2 Nevertheless, one important draw-
back is the foul odor of the volatile dimethyl sulfide
produced, which is regulated by the offensive odor
control law. From an environmental standpoint, the
need for odorless substitutes for foul-smelling molecules
like dimethyl sulfide is therefore great. In order to
circumvent this problem, substitutes for the original
dimethyl sulfoxide, like 6-methylsulfinylhexanoic acid
and its polymer-supported derivatives,3 are constantly
being sought. Recently, Crich and Neelamkavil devised
a fluorous Swern oxidation using tridecafluorooctyl
methyl sulfoxide for this purpose.4 The development of
a new odorless Swern oxidation is, however, still needed
for researchers in the laboratory as well as in the
chemical industry setting.
found that the dodecyl methyl sulfide was also odorless
and used it in the debenzylation of esters. This result
prompted us to develop a new odorless Swern oxida-
tion. Herein we report new protocols for odorless Swern
oxidation and Corey–Kim oxidation using dodecyl
methyl sulfoxide or sulfide, respectively.
The process of a new odorless Swern oxidation is
illustrated in Scheme 1. Dodecyl methyl sulfoxide (1)7
was easily prepared in high yields by methylation of
1-dodecanethiol (2) with methyl iodide followed by
oxidation with sodium periodate in chloroform–water
catalyzed by a phase transfer catalyst. The dodecyl
methyl sulfide (3)6,7 and the sulfoxide 1 are odorless,
namely, this modified Swern oxidation procedure is free
from the malodorous dimethyl sulfide produced in the
original Swern oxidation. In addition, the less polar
and fairly high boiling-point sulfide 3 (bp 110°C/0.2
mmHg) is easily separable by silica gel chromatography
and can be reused by re-oxidation to the sulfoxide 1.
HS
2
K2CO3
DMF
CH3I
93%
Recently, we have also been involved in a program
aimed at developing odorless thiols and sulfides that
can be used in organic reactions as substitutes for the
usual foul-smelling thiols5 and sulfides. We have per-
formed a study on a formal asymmetric Michael addi-
tion of hydrogen sulfide to a-substituted a,b-unsatu-
rated carbonyl compounds using odorless 10-mercap-
toisoborneol and 1-dodecanethiol.6 In this study, we
S
R1
3
O
R2
R1
(COCl)2
NaIO4 99%
OH
R2
S
Keywords: odorless Swern oxidation; dodecyl methyl sulfoxide; odor-
less Corey–Kim oxidation; dodecyl methyl sulfide.
* Corresponding author. Tel.: +81-75-595-4639; fax: +81-75-595-4775;
e-mail: node@mb.kyoto-phu.ac.jp
1
O
Scheme 1. A new odorless Swern oxidation.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00968-1

5178
K. Nishide et al. / Tetrahedron Letters 43 (2002) 5177–5179
Table 1. Odorless Swern oxidation of alcohols using dode-
cyl methyl sulfoxide (1)
In order to optimize the reaction conditions for a new
odorless Swern oxidation [sulfoxide 1–oxalyl chloride],
an oxidation of benzhydrol was carried out first under
the original Swern oxidation conditions1 (−60°C to rt, 2
h, after addition of triethylamine) to give benzophen-
one (51%) accompanied by the recovered alcohol
(42%). It was suggested that longer reaction times and
keeping the reaction temperature at about −40°C after
addition of triethylamine were necessary to generate a
sufficient amount of the sulfonium ylide intermediate
and to prevent the undesired Pummerer rearrange-
ment.3a A high yield (95%) of benzophenone was
obtained under a prolonged reaction time (200 min) at
−60 to −40°C after addition of triethylamine. The reac-
tions in other solvents (THF, toluene, ether) afforded
benzophenone in moderate to low yields (49, 53 and
10%), respectively. The results of the new odorless
Swern oxidation8 using the sulfoxide 1 and oxalyl chlo-
ride are summarized in Table 1. All benzylic, allylic,
and aliphatic primary and secondary alcohols were
oxidized smoothly to aldehydes or ketones in high
yields.
yield (%)a
aldehyde
conditions (temp. and
time after Et3N addition)
substrate
recovery of
Dod-S-Me
or ketone
(lit.)b
-60°C ~ -40°C (3.33 h)
-40°C ~ r. t. (1 h)
95 (98)
100
94
OH
OH
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
91 (95)
O
Br
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
95
95
93
OH
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
OH
93 (98)
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
93 (95)
93 (99)
89
99
OH
The other oxidation of alcohols using dimethyl sulfide
and N-chlorosuccinimide is known as the Corey–Kim
oxidation.9 Instead of using the dimethyl sulfide, we
applied the dodecyl methyl sulfide (3) to this oxidation.
The results of the new odorless Corey–Kim oxidation10
were compiled in Table 2. From the standpoint of the
chemical industry setting, toluene as a solvent was
tested instead of dichloromethane. The yields of the
corresponding aldehydes or ketones were excellent in
both solvents.
-60°C ~ -40°C (5 h)
-40°C ~ r. t. (1 h)
OH
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
H
91 (95)
81 (98)
91
95
OH
-60°C ~ -40°C (2 h)
-40°C ~ r. t. (40 min)
OH
a) Isolated yields. b) See ref. 2c.
The two protocols described for the oxidation of alco-
hols were performed without foul smelling in the labo-
ratory. Since dodecyl methyl sulfide (3) has a higher
boiling point than volatile dimethyl sulfide, the prod-
ucts of the oxidation were isolated by column chro-
matography in the case of neutral alcohols.11 However,
chromatographic isolation of the products should be
avoided in large-scale reactions. In the case of acidic
alcohols, for example, odorless Swern oxidation of
mandelic acid gave phenylglyoxylic acid in 96% yield by
sequential extraction of the reaction mixture after
basification and acidification.12
Table 2. Odorless Corey–Kim oxidation of alcohols using
dodecyl methyl sulfide (3)
NCS (3 equiv.)
Dod-S-Me (3, 3 equiv.)
aldehydes
alcohols
or ketones
yield (%)a
Et3N (5 equiv.)
-40°C (14 h)
in CH2Cl2
in toluene
In conclusion, we were able to provide new odorless
protocols for the Swern oxidation and the Corey–Kim
oxidation using the dodecyl methyl sulfoxide (1) or the
dodecyl methyl sulfide (3), respectively. These protocols
furnish the products under odorless experimental condi-
tions at minimal cost. The starting material 1-dode-
canethiol (2) for the synthesis of the odorless sulfoxide
(1) and the sulfide (3) is inexpensive (about $20/kg)
because it is used in bulk as a vulcanizing agent for
rubber. The odorless reagents 2 and 3 can therefore be
prepared at a more moderate price than the other new
sulfoxides3,4 or the new oxidizing reagent13 recently
developed. We believe that the odorless feature of these
protocols is important for environmental chemistry as
well as for organic chemistry. Further studies utilizing
odorless sulfides and sulfoxides are underway in our
laboratory.
95
98
OH
OH
b
90
99
91
O
OH
OMe
OBn
BnO
99
91
95
CH2OH
OH
97
O
a) Isolated yields. b) The starting material was insoluble.

K. Nishide et al. / Tetrahedron Letters 43 (2002) 5177–5179
5179
Acknowledgements
brine, dried (Na2SO4), filtered, and concentrated in
vacuo. Purification of the residue by silica gel column
chromatography (hexane/ethyl acetate=40/1) gave ben-
zophenone (47 mg, 95% yield) and dodecyl methyl sulfide
(3) (60 mg, 100% yield).
We are grateful for a Grant-in-Aid from the Ministry
of Education, Science, Sports and Culture of Japan, for
partial financial support of this research.
The 10-times scale-up experiment under the above condi-
tions using benzhydrol (500 mg, 2.7 mmol) gave ben-
zophenone (460 mg, 93% yield), accompanied with
dodecyl methyl sulfide (3) (540 mg, 92% yield).
9. Corey, E. J.; Kim, C. U. J. Am. Chem. Soc. 1972, 94,
7586–7587.
References
1. (a) Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org.
Chem. 1978, 43, 2480–2482; (b) Marx, M.; Tidwell, T. T.
J. Org. Chem. 1984, 49, 788–793.
2. (a) Lee, T. V. Comprehensive Organic Synthesis; Trost, B.
M.; Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 7, pp. 291–303. Reviews: (b) Tidwell, T. T. Org.
React. 1990, 39, 297–572; (c) Mancuso, A. J.; Swern, D.
Synthesis 1981, 165–185; (d) Tidwell, T. T. Synthesis
1990, 857–870.
3. (a) Liu, Y.; Vederas, J. C. J. Org. Chem. 1996, 61,
7856–7859; (b) Harris, J. M.; Liu, Y.; Chai, S.; Andrews,
M. D.; Vederas, J. C. J. Org. Chem. 1998, 63, 2407–2409.
4. Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001, 123,
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5. Node, M.; Kumar, K.; Nishide, K.; Ohsugi, S.;
Miyamoto, T. Tetrahedron Lett. 2001, 42, 9207–9210.
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10. A typical procedure for the new odorless Corey–Kim oxi-
dation using dodecyl methyl sulfide (3): To
dichloromethane or toluene solution (10 ml) of N-chloro-
succinimide (108 mg, 0.81 mmol) was added
a
a
dichloromethane or toluene solution (2 ml) of dodecyl
methyl sulfide (3) (176 mg, 0.81 mmol) dropwise at
−40°C, and the resulting mixture was stirred for 30 min.
A dichloromethane or toluene solution (2 ml) of benzhy-
drol (50 mg, 0.27 mmol) was added dropwise at −40°C.
After the mixture was stirred for 2 h, triethylamine (189
ml, 1.36 mmol) was added dropwise at −40°C. After
stirring for 14 h, water (20 ml) was added to the reaction
mixture. The mixture was neutralized with 1N HCl (0.5
ml), followed by extraction of the aqueous layer with
chloroform (40 ml×3) or ethyl acetate (40 ml×3). The
combined organic layer was washed with brine, dried
(Na2SO4), filtered, and concentrated in vacuo. Silica gel
chromatography of the residue (hexane/ethyl acetate=
40/1) gave benzophenone (47 mg, 95% yield in
dichloromethane or 49 mg, 98% yield in toluene, respec-
tively).
7. Dodecyl methyl sulfoxide (1) and dodecyl methyl sulfide
(3) will be available in the near future from Wako Pure
Chemical Industries, Ltd.
8. A typical procedure for the new odorless Swern oxidation
using dodecyl methyl sulfoxide (1): To a dichloromethane
(4 ml) suspension of dodecyl methyl sulfoxide (1) (95 mg,
0.41 mmol) was added dropwise oxalyl chloride (1.0 M
dichloromethane solution, 0.41 ml, 0.41 mmol) at −60°C,
and the resulting mixture was stirred for 15 min. A
dichloromethane (1 ml) solution of benzhydrol (50 mg,
0.27 mmol) was added dropwise at −60°C. The mixture
was stirred for 30 min, triethylamine (189 ml, 1.36 mmol)
was added dropwise, and the resultant mixture was grad-
ually warmed to −40°C in 200 min. The reaction mixture
was then warmed to room temperature by removing the
cooling bath and stirred for 1 h. The mixture was
quenched with water (10 ml), and neutralized with an 1N
HCl (0.5 ml) solution, then extracted with chloroform (40
ml×3). The combined organic layer was washed with
The 20-times scale-up experiment under the above condi-
tions using benzhydrol (1.0 g, 5.43 mmol) gave benzophe-
none (953 mg, 96% yield).
11. Depending on the physical property and the amounts of
the products, extraction, crystallization, or distillation
could be used for isolation of the products.
12. The same extraction in the case of Corey–Kim oxidation
gave a mixture of phenylglyoxylic acid and succinimide.
13. (a) Matsuo, J.; Iida, D.; Tatani, K.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 2002, 75, 223–234; (b) Mukaiyama, T.;
Matsuo, J.; Iida, D.; Kitagawa, H. Chem. Lett. 2001,
846–847; (c) Matsuo, J.; Kitagawa, H.; Iida, D.;
Mukaiyama, T. Chem. Lett. 2001, 150–151; (d)
Mukaiyama, T.; Matsuo, J.; Yanagisawa, M. Chem. Lett.
2000, 1072–1073.