New non-volatile and odorless organosulfur compounds anchored on ionic liquids. Recyclable reagents for Swern oxidation

Article abstract of DOI:10.1016/j.tet.2006.01.045

A new class of odorless and non-volatile organosulfur compounds grafted to imidazolium ionic liquid scaffold has been synthesized. The sulfoxides can be used effectively for the oxidation of primary allylic and benzylic alcohols into aldehydes and secondary alcohols to ketones under Swern oxidation conditions and the corresponding sulfides can be recovered and recycled.

Full text of DOI:10.1016/j.tet.2006.01.045

Tetrahedron 62 (2006) 3389–3394
New non-volatile and odorless organosulfur compounds anchored
on ionic liquids. Recyclable reagents for Swern oxidation
Xun He and Tak Hang Chan
*
Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6
Received 23 October 2005; revised 13 January 2006; accepted 13 January 2006
Available online 3 February 2006
Abstract—A new class of odorless and non-volatile organosulfur compounds grafted to imidazolium ionic liquid scaffold has been
synthesized. The sulfoxides can be used effectively for the oxidation of primary allylic and benzylic alcohols into aldehydes and secondary
alcohols to ketones under Swern oxidation conditions and the corresponding sulfides can be recovered and recycled.
q 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
bromoalkyl alcohols 2 (Scheme 1). The reaction was
conducted without solvent at 60–70 8C and the product 3
was obtained in nearly quantitative yield simply by
washing the reaction mixture with diethyl ether to
remove the trace amount of unreacted starting materials.
This was followed by anion exchange to give the triflate
salt 4 quantitatively. Mass spectroscopic analysis showed
that the anion exchange was complete based on the
spectra on anions, which showed the absence of bromide
anion. Sodium triflate also worked for the anion
exchange reaction, but the reaction went faster with
silver triflate. The methanesulfonylation of alcohols 4
was conducted at room temperature under the basic
condition provided by Cs CO in acetonitrile. This gave
Organosulfur compounds have played an important role
in organic chemistry. An array of organosulfur compounds
1
2
have been introduced for use in pesticides, medicines, and
3
more recently material sciences. Many organosulfur reagents
4
have important use in synthetic organic chemistry. Volatile
organosulfur compounds, especially thiols, often have very
unpleasant smells and some are toxic. These properties have
2
reduced their attractiveness for applications. We report here
the synthesis of a new class of organosulfur compounds
anchored on the imidizolium scaffold commonly used for
ionic liquids. Ionic liquids have received much attention in
recent years as environmentally benign reaction media for
2
3
5
organic reactions. This is due to some intriguing properties
excellent yields of product mesylates 5. The inorganic
salt was simply removed by filtration and the organic
impurity was easily washed away with diethyl ether. The
mesylates 5 were then transformed to the ionic liquid-
supported sulfides 10 in one pot with a sequence of
reactions but without need of purification of the
intermediate products. First, treatment of 5 with thiourea
of ionic liquids: high thermal and chemical stability,
non-flammability, lack of measurable vapor pressure and
highloadingcapacity. Bymodifying the structure ofthe cation
or the anion, the solubilities of the ionic liquids can be tuned
readily so that they can phase separate from organic as well
as aqueous media. By anchoring the sulfur function to the
ionic liquid moiety, we expect to render the organosulfur
compounds non-volatile, and easily recoverable and
recyclable. We then demonstrate the application of these
new organosulfur compounds as reagents for the Swern
oxidation.
6
in acetonitrile gave the thiouronium salt 6. Base
hydrolysis of 6 gave the odorless ionic liquid-supported
thiol 8 together with the disulfide 9 as a mixture. The
sole formation of pure thiol 8 was difficult even though a
number of reaction conditions were tested including
using different bases such as LiOH, NaOH, KOH and
CsOH, or solvents such as THF and acetonitrile, and
temperature from room temperature to 60 8C. This is due
to ease of thiol oxidative dimerization in air under basic
conditions. However, we were able to trap the thiolate
intermediate 7 readily as the methyl sulfide 10 by
quenching the base hydrolytic reaction mixture with
2
. Results and discussion
The preparation of the ionic liquid-supported sulfur
compounds started from 1,2-dimethylimidazole 1 and
Keywords: Odorlessorganosulfur compounds; Ionic liquids; Swern
oxidation; Supported reagents.
Corresponding author. Tel.: C514 398 2094;
e-mail: tak-hang.chan@mcgill.ca
7
dimethyl sulfate. The conversion of the ionic liquid 4
to the sulfur compound 10 could be achieved in O92%
overall yield with no need of chromatographic
*
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.045

3390
X. He, T. H. Chan / Tetrahedron 62 (2006) 3389–3394
Me
Me
OH
6
0 – 70 °C
OH
1
. Br
n
Me
N
N
n
Me
N
N
X
2
. AgOTf, CH CN
3
3
: X=Br;
4: X=TfO
MsCl
Cs2CO3
CH CN
1
2
2
2
a: n=1;
b:n=2;
c: n=5
3
Me
Me
1
, Thiourea, CH CN, reflux
OMs
n
3
SMe
n
Me
N
N
TfO
Me
N
N
TfO
2, NaOH/H O
2
5
3
, Me SO
2
4
10
H IO
5
6
Me
Me
CH3OH
°C - rt
+
0
S
S
n
Me
N
N
C(NH2)2 Me
N
N
N
n
Me
TfO
Ox
S
n
TfO
MsO
6
7
Me
N
N
TfO
Me
Me
Me
SH
n
S
n
Me
N
N
TfO
Me
N
1
1
1: x=1
2: x=2
TfO
2
8
9
Scheme 1. Preparation of ionic liquid-grafted sulfides and sulfoxides.
purification of intermediates and there was no foul smell
released in any of the operations. This is because in all
the reaction steps, the products were separated from the
excess organic or inorganic reagents by simply washing
with organic or aqueous solvents, an advantage, which
we have demonstrated previously in ionic liquid-
been used extensively for that purpose. A major drawback
of the Swern oxidation is that dimethyl sulfide, generated in
stoichiometric amount, is volatile, malodorous, toxic and
difficult to be recovered. This mitigates against its use on a
large scale. A number of research groups have attempted to
overcome the problem by using polymer-supported sulf-
8
9
15
16
supported synthesis of small molecules, oligopeptides
oxide reagents, fluorous sulfoxides or dodecyl methyl
sulfoxide. Each of these has some inherent deficiencies. In
1
0
17
and oligosaccharides. The whole synthetic sequence
was odor-free as no volatile organosulfur compounds
were used or generated. Previously, sulfur containing
imidazolium ionic liquid had been synthesized from
the dodecyl methyl sulfoxide case, recovery of the product
sulfide was difficult. The fluorous sulfoxides and sulfides are
likely to be expensive and relatively volatile. Polymer-
1
5
1
1
supported sulfoxide reagents, whether using insoluble or
soluble polymer support, usually have a low loading level of
the effective functional group.
N-methylimidazole and 2-(chlorethyl)ethyl sulfide.
However, this involved the use of odorous volatile sulfur
compound for the synthesis, and ethyl sulfoxides in
general are not used for Swern oxidation.
We examined therefore the ionic liquid-supported sulf-
oxides 11 as recoverable and recyclable reagents for the
Swern oxidation reaction (Scheme 2).
The oxidation of the sulfides 10 with periodic acid generated
very cleanly the sulfoxides 11 without over-oxidation to the
1
2
sulfone 12 under the experimental condition. Potassium
periodate did not oxidize 10 under neutral conditions, but
under acidic conditions converted 10 to a mixture of
sulfoxide 11 as well as sulfone 12 in a ratio of 3 to 1
H IO
5
6
1
according to H NMR spectra. m-Chloroperoxybenzoic acid
(
Me
Me
O
mCPBA) also oxidized the sulfide 10 to give similar results
S
Me N
N
S
n Me
Me N
N
n Me
as acidified potassium periodate. The oxidation of the
sulfides with peracetic acid, on the other hand, proceeded
slowly at room temperature. It only generated a very small
amount of sulfoxide 11 after stirring for 24 h at room
temperature.
TfO
TfO
10
11
(
COCl) /Et N
2 3
O
OH
1
2
1
2
R
R (H)
R
R (H)
The conversion of alcohols to aldehydes and ketones is one
of the key functional transformations in organic chemistry.
Scheme 2. Recycle of ionic liquid-supported sulfides and sulfoxides in
Swern oxidation.
1
3,14
The Swern oxidation and its numerous variations
have

X. He, T. H. Chan / Tetrahedron 62 (2006) 3389–3394
3391
The Swern oxidations were conducted under standard
conditions, using oxalyl chloride as activator and
triethylamine as base in acetonitrile/dichloromethane at
low temperature. The ionic liquid-attached sulfoxides 11b
or 11c were quite reactive. A number of alcohols were
converted to the corresponding aldehydes or ketones in
high yields (Table 1). The carbonyl product was easily
separated from the ionic liquid anchored sulfide 10 (b or
c) by simple phase separations with diethyl ether after
Swern oxidation. However, it should be pointed out that
the sulfoxide 11a, which has two methylene spacers
between the ionic liquid moiety and the sulfoxide part,
did not work well as Swern oxidation reagent. It is
possible that facile b elimination may have occurred
leading to the fragmentation of the imidazolium moiety
from the sulfoxide. The oxidation of secondary alcohols
to the corresponding ketones worked very efficiently
under the reaction conditions (Table 1). On the other
hand, oxidation of primary alcohols to aldehydes appears
to have worked well only for benzylic or allylic alcohols.
Simple aliphatic primary alcohols tended to give low
yield, possibly because the sulfoxide 11b or 11c reagent
was not employed in large excess, in contrast to what
was normally used for DMSO. We have conducted one
reaction on a larger (10–50 mmol) scale for the oxidation
of benzhydrol to benzophenone. The isolated yield of the
product was 91%.
1
4
The use of ionic liquid-supported reagents allows for the
opportunity of recovery and recycle. The sulfide 10b or
10c, insoluble in ether, was recovered after aqueous
treatment with K CO and extraction with acetonitrile/
2 3
1
8
dichloromethane. The recovered sulfide 10b or 10c can
be re-oxidized with periodic acid and used for the Swern
oxidation again. Oxidation of benzhydrol to benzophe-
none was chosen as an example to test the recovery and
recycling efficiency of the 11b410b system. The results
are summarized in Table 2, which show that the product
yields and recovered sulfide yields were still quite
1
8
acceptable after four recycles (Table 2).
Table 1. Swern oxidation using ionic liquid-supported sulfoxides
Entry
1
Sulfoxide
Substrate
Product
Yield (%)
90
11b
OH
O
2
11b
OH
O
95
3
4
11b
11b
OH
O
86
85
Br
Br
HO
O
O
O
5
6
11b
11b
CHO
88
95
OH
OH
CHO
OBn
OBn
7
8
11b
11b
OH
O
O
O
82
85
Me
Me
Me
Me
Me
H
Me
H
H
H
H
H
O
HO
H
H
9
11b
11c
Me
Me
Me
90
95
Me
Me
Me
O
OH
10
OH
O
1
1
1
2
11c
11c
OH
O
82
97
MeO
MeO
CHO
OH
OMe
OMe

3392
X. He, T. H. Chan / Tetrahedron 62 (2006) 3389–3394
Table 2. Recycle of ionic liquid-supported sulfide 10b in Swern oxidation
of benzhydrol to benzophenone
58.1, 45.2, 34.9, 31.6, 9.1; HRMS (ESI): calcd for
C H N O (M ) 155.1179, found: 155.1180.
C
8
15 2
OH
O
(
COCl)2
0
flate (4a). Yield: 100% as clear liquid; H NMR (400 MHz,
+
11b
+
10b
4.1.3. 1-(2 -Hydroxyethyl)-2,3-dimethylimidazolium tri-
1
Et N
3
D O): d 7.28 (d, 1H, JZ2.0 Hz), 7.24 (d, 1H, JZ2.0 Hz),
2
4
2.51 (s, 3H); C NMR (300 MHz, D O): d 144.5, 122.5,
.15 (t, 2H, JZ5.6 Hz), 3.82 (t, 2H, JZ6 Hz), 3.69 (s, 3H),
Recycle times
Product yield (%)
Recovered sulfide (%)
1
90
88
2
87
82
3
86
82
4
81
80
13
2
121.2, 60.2, 50.4, 35.0, 9.4; HRMS (ESI): calcd for
C H N O (M ) 141.1018, found: 141.1022.
C
7
13 2
3. Conclusions
0
.1.4. 1-(6 -Hydroxyhexyl)-2,3-dimethylimidazolium tri-
flate (4c). Yield: 100% as clear liquid; H NMR (300 MHz,
4
1
We have prepared a class of novel sulfur containing
compounds anchored onto an imidazolium ionic liquid
scaffold. Because of the lack of vapour pressure of these
ionic liquids, the sulfur compounds do not possess odor. The
sulfoxide compounds 11b and 11c can be used effectively
for the oxidation of alcohols to carbonyl compounds under
the Swern oxidation conditions. The product sulfide 10b can
be recovered easily from the reaction mixture and
regenerated to 11b and thus reused for at least 4 cycles.
D O): d 7.21 (d, 1H, JZ2.4 Hz), 7.17 (d, 1H, JZ2.4 Hz),
2
3
6
4
6
.98 (t, 2H, JZ6.9 Hz), 3.64 (s, 3H), 3.46 (t, 2H, JZ
.6 Hz), 2.46 (s, 3H), 1.70 (m, 2H), 1.42 (m, 2H), 1.23 (m,
13
H); C NMR (300 MHz, D O): d 144.2, 122.2, 120.8,
1.9, 48.3, 34.8, 31.4, 29.2, 25.5, 24.9, 9.1; HRMS (ESI):
2
C
calcd for C H N O (M ) 197.1648, found: 197.1646.
1 21 2
1
4
1
.1.5. Compound 5b. To a flask containing 4b (6.00 g,
9.7 mmol) and cesium carbonate (8.05 g, 24.7 mmol) was
added acetonitrile (30 mL). The mixture was cooled to 0 8C
and methanesulfonyl chloride (2.30 mL, 29.6 mmol) was
added dropwise. After 2 h of stirring at 0 8C, the mixture
was warmed to room temperature and stirring continued for
4. Experimental
2
0 h. The insoluble inorganic salt was filtered off and the
4
.1. General
filtrate was evaporated by rotary evaporation and dried in
vacuo overnight. The crude product was washed with
diethyl ether for four times to afford white solid product 5b
The procedures to make ionic liquid-attached compounds
with two, three, six methylene spacers in the Scheme 1 were
the same.
1
(7.31 g, 97% yield). Mp 47–49 8C; H NMR (400 MHz,
D O): d 7.25 (d, 1H, JZ2.0 Hz), 7.21 (d, 1H, JZ2.0 Hz),
2
4
3
.23 (t, 2H, JZ5.6 Hz), 4.16 (t, 2H, JZ7.2 Hz), 3.64 (s,
H), 3.06 (s, 3H), 2.46 (s, 3H), 2.19 (m, 2H); C NMR
0
triflate (4b). To a flask containing 1,2-dimethylimidazole
4
.1.1. 1-(3 -Hydroxypropyl)-2,3-dimethylimidazolium
13
(400 MHz, D O): d 144.7, 122.6, 120.9, 68.2, 44.8, 36.6,
2
(
(
10.0 mL, 113 mmol) was added 3-bromopropanol
10.0 mL, 114 mmol). The mixture was heated to 70 8C
C
4.9, 28.8, 9.2; HRMS (ESI): calcd for C H N O S (M )
9 17 2 3
33.0954, found: 233.0953.
3
2
and stirred for 2 h under nitrogen and then cooled to room
temperature. The crude product solidified during the cooling
process. The solid was washed with diethyl ether for four
times and dried in vacuo for 3 h to afford
1
.1.6. Compound 5a. Yield: 94% as clear liquid; H NMR
4
(
400 MHz, D O): d 7.30 (d, 1H, JZ1.6 Hz), 7.23 (d, 1H,
2
JZ1.6 Hz), 4.51 (t, 2H, JZ4.8 Hz), 4.42 (t, 2H, JZ5.6 Hz),
1
3
3
.65 (s, 3H), 3.05 (s, 3H), 2.49 (s, 3H); C NMR (400 MHz,
D O): d 145.4, 122.8, 121.3, 68.6, 47.3, 36.9, 35.1, 9.5;
2
0
bromide (3b). As white solid (26.2 g, 98% yield). Mp
4
.1.2. 1-(3 -Hydroxypropyl)-2,3-dimethylimidazolium
C
HRMS (ESI): calcd for C
found: 219.0798.
H
N
O
S (M ) 219.0795,
8
15
2
3
1
5
8–60 8C; H NMR (400 MHz, D O): d 7.24 (d, 1H, JZ
2
2
Hz), 7.20 (d, 1H, JZ2 Hz), 4.10 (t, 2H, JZ7.2 Hz), 3.65
1
4.1.7. Compound 5c. Yield: 95% as clear liquid; H NMR
(
s, 3H), 3.50 (t, 2H, JZ6.4 Hz), 2.48 (s, 3H), 1.93 (m, 2H);
1
3
C NMR (300 MHz, D O): d 144.5, 122.4, 120.9, 58.2,
5.3, 35.0, 31.6, 9.4; HRMS (ESI): calcd for C H N O
(400 MHz, D O): d 7.16 (d, 1H, JZ2.4 Hz), 7.12 (d, 1H,
2
2
4
(
JZ2.4 Hz), 4.15 (t, 2H, JZ6.0 Hz), 3.94 (t, 2H, JZ7.2 Hz),
3.58 (s, 3H), 3.00 (s, 3H), 2.41 (s, 3H), 1.68 (m, 2H), 1.59
8
15 2
C
M ) 155.1179, found: 155.1178.
1
3
m, 2H), 1.28 (m, 2H), 1.17 (m, 2H); C NMR (400 MHz,
(
CD CN): d 144.6, 122.5, 121.0, 71.1, 48.4, 36.8, 35.1, 29.5,
0
zolium bromide (3b) (4.97 g, 21.1 mmol) in dry acetonitrile
To a solution of 1-(3 -hydroxypropyl)-2,3-dimethylimida-
3
28.9, 25.6, 25.0, 9.6; HRMS (ESI): calcd for C12H N O S
23 2 3
C
(M ) 275.1424, found: 275.1420.
(
20 mL) was added silver triflate (5.43 g, 21.1 mmol). The
mixture was stirred for 2 h in the dark under nitrogen. The
mixture was filtered to remove the yellow salt and
the filtrate was evaporated by rotary evaporation under
vacuum and dried in vacuo to generate the product 4b as a
4.1.8. Compound 10b. To a flask containing 5b (1.00 g,
2.61 mmol) and thiourea (0.32 g, 4.20 mmol) was added dry
acetonitrile (20 mL). The mixture was refluxed for 10 h
under nitrogen. After removing the solvent, NaOH (0.42 g,
10.5 mmol) and degassed water (20 mL) were added and the
mixture was stirred at 45 8C overnight under nitrogen.
Dimethyl sulfate (0.30 mL, 3.15 mmol) was added and
the mixture was stirred at room temperature for 20 h.
clear liquid with a very light brown color (6.42 g, 100%
1
yield). H NMR (300 MHz, D O): d 7.27 (d, 1H, JZ
2
1
3
2
.8 Hz), 7.23 (d, 1H, JZ1.8 Hz), 4.12 (t, 2H, JZ7.2 Hz),
.68 (s, 3H), 3.53 (t, 2H, JZ6.3 Hz), 2.51 (s, 3H), 1.96 (m,
1
H); C NMR (300 MHz, D O): d 144.5, 122.4, 120.9,
3
2

X. He, T. H. Chan / Tetrahedron 62 (2006) 3389–3394
3393
After the pH of the mixture was adjusted to 7 with the
addition of aqueous HCl, the mixture was freeze dried to
remove water. Acetonitrile was added to the residue to
extract the product. The acetonitrile solution was filtered to
remove the insoluble inorganic salt, and the filtrate was
rotary evaporated under vacuum and then dried in vacuo to
(m, 2H), 2.52 (s, 3H), 2.42 (s, 3H), 1.67 (m, 2H), 1.58 (m,
2H), 1.35 (m, 2H), 1.19 (m, 2H); C NMR (400 MHz,
D O): d 144.2, 122.2, 120.8, 52.8, 48.3, 36.7, 34.9, 29.0,
2
1
3
27.5, 25.4, 22.0, 9.2; HRMS (ESI): calcd for C H N SO
12 23 2
C
(M ) 243.1526, found: 243.1525.
1
give product 10b as clear oil (0.87 g, 99% yield). H NMR
400 MHz, D O): d 7.22 (d, 1H, JZ2.4 Hz), 7.17 (d, 1H,
4.2. General procedure for the Swern oxidation
(
2
JZ2.4 Hz), 4.08 (t, 2H, JZ6.8 Hz), 3.62 (s, 3H), 2.47 (s,
A solution of ionic liquid-attached sulfoxide 11 (0.9 mmol,
3 equiv) in dichloromethane (2.5 mL) and acetonitrile
(2.5 mL) was cooled to K78 8C and oxalyl chloride
(0.9 mmol, 3 equiv) was added dropwise. The mixture was
stirred at K78 8C for 40 min and then the alcohol
1
3
3
H), 2.41 (t, 2H, JZ6.8 Hz), 1.97 (m, 5H); C NMR
(
2
300 MHz, D O): d 144.5, 122.5, 120.8, 46.9, 34.9, 29.9,
C
8.3, 14.4, 9.2; HRMS (ESI): calcd for C H N S (M )
9 17 2
2
1
85.1107, found: 185.1103.
(
0.3 mmol, 1 equiv) solution in dichloromethane (2.5 mL)
1
.1.9. Compound 10a. Yield: 99% as clear oily liquid; H
4
was added dropwise in 10 min. After stirring at low
temperature for 1.5 h, triethylamine (0.25 mL, 6 equiv)
was added and the mixture was slowly warmed to room
temperature. The solvent was removed by rotary evapor-
ation and the product in the residue was extracted with
diethyl ether (6 mL) for five times. The ether extract was
evaporated by rotary evaporation in vacuo. The product
residue was subject to flash column chromatography (silica
gel 60A, 230–400 mesh) using hexane and ethyl acetate as
eluant to afford the pure product.
NMR (400 MHz, D O): d 7.28 (d, 1H, JZ2.0 Hz), 7.21 (d,
2
1
(
(
1
1
H, JZ2.0 Hz), 4.22 (t, 2H, JZ6.4 Hz), 3.66 (s, 3H), 2.83
13
t, 2H, JZ6.4 Hz), 2.51 (s, 3H), 1.99 (s, 3H); C NMR
400 MHz, D O): d 144.7, 122.4, 121.1, 47.2, 35.0, 33.4,
2
C
4.7, 9.4; HRMS (ESI): calcd for C H N S (M )
8 15 2
71.0950, found: 171.0949.
1
.1.10. Compound 10c. Yield: 98% as clear oily liquid; H
4
NMR (300 MHz, D O): d 7.16 (d, 1H, JZ1.8 Hz), 7.13 (d,
2
1
H, JZ1.8 Hz), 3.94 (t, 2H, JZ7.2 Hz), 3.60 (s, 3H), 2.42
(
s, 3H), 2.36 (t, 2H, JZ7.2 Hz), 1.92 (s, 3H), 1.65 (m, 2H),
4.3. Swern oxidation in larger scale
1
.43 (m, 2H), 1.52 (m, 4H); C NMR (300 MHz, D O): d
3
1
1
1
2
2
44.2, 122.2, 120.8, 48.3, 34.7, 33.4, 29.1, 28.3, 27.6, 25.3,
4.4, 9.1; HRMS (ESI): calcd for C H N S (M )
27.1576, found: 227.1575.
A solution of ionic liquid-attached sulfoxide 11b (16.73 g,
48 mmol) in dichloromethane (50 mL) and acetonitrile
(75 mL) was cooled to K78 8C and oxalyl chloride
C
1
2 23 2
(4.8 mL, 55 mmol) was added dropwise. The mixture was
4
1
.1.11. Compound 11b. To a solution of 10b (5.05 g,
5.1 mmol) in methanol (50 mL), which was cooled with
stirred at K78 8C for 40 min and then the alcohol benzhydrol
(2.92 g, 16 mmol) solution in dichloromethane (25 mL) was
added dropwise in 10 min. After stirring at low temperature
for 1.5 h, triethylamine (14 mL, 100 mmol) was added and
the mixture was slowly warmed to room temperature in 2 h.
The solvent was removed by rotary evaporation and the
product in the residue was extracted with diethyl ether
(60 mL) for 10 times. The ether extract was evaporated by
rotary evaporation in vacuo. The product residue was subject
to flash column chromatography (silica gel 60A, 230–400
mesh) using hexane and ethyl acetate as eluant to afford the
product benzophenone (2.62 g, 91% yield).
ice bath, was added dropwise a solution of periodic acid
3.45 g, 15.1 mmol) in methanol (15 mL). The mixture was
(
stirred at 0 8C for 2 h. The ice bath was removed and stirring
was continued for 20 h. To the orange mixture was added
aqueous Na S O solution until the orange color disap-
peared. The solvent methanol was removed by rotary
evaporation in vacuo and water was removed by freeze
drying. To the residue was then added the mixed solvent
2
2 3
(
100 mL) of acetonitrile and dichloromethane (v/vZ1:1).
After filtering off the inorganic salt, the filtrate was rotary
evaporated under vacuum and dried in vacuo to afford the
product as white sticky foam (5.18 g, 98% yield). H NMR
1
4.4. General procedure to recover ionic liquid-attached
sulfide after Swern oxidation
(
400 MHz, D O): d 7.24 (d, 1H, JZ2 Hz), 7.17 (d, 1H, JZ
2
2
2
Hz), 4.14 (t, 2H, JZ7.2 Hz), 3.61 (s, 3H), 2.84–2.72 (m,
13
H), 2.56 (s, 3H), 2.45 (s, 3H), 2.15 (m, 2H); C NMR
After the extraction of the product with diethyl ether
described above, water (10 mL) was added to the residue.
The aqueous phase was collected and to which K CO
3
(
400 MHz, D O): d 144.6, 122.7, 120.8, 49.1, 46.9, 37.1,
2
C
3
5.1, 23.0, 9.4; HRMS (ESI): calcd for C H N SO (M )
9 17 2
2
2
01.1056, found: 201.1056.
(0.16 g, 1.1 mmol) was added. The aqueous phase was
stirred for 3 h at room temperature and water was removed
by freeze–dry by lypholyser. To the solid residue was then
added acetonitrile (10 mL), dichloromethane (5 mL) and
anhydrous Na SO . The mixture was stirred for 20 min to
extract the expected sulfide into the organic phase. After
filtering off the insoluble inorganic salts, the organic filtrate
was evaporated by rotary evaporation under vacuum and
dried in vacuo to generate the recovered ionic liquid-
attached sulfide 10 (Table 2). The NMR spectra of the
recovered sulfide showed the same NMR as that of 10
before reaction. The recovered sulfide was used as is for the
next cycle. The recovery yield was about 80%, due to
1
.1.12. Compound 11a. Yield: 99% as thick oil; H NMR
4
(
400 MHz, D O): d 7.33 (d, 1H, JZ2.4 Hz), 7.26 (d, 1H,
2
JZ2.4 Hz), 4.53 (t, 2H, JZ6.0 Hz), 3.68 (s, 3H), 3.33 (m,
2
4
1
3
H), 3.24 (m, 1H), 2.68 (s, 3H), 2.55 (s, 3H); C NMR
1
(
300 MHz, D O): d 144.9, 123.0, 121.0, 52.1, 42.3, 37.5,
2
C
5.2, 9.5; HRMS (ESI): calcd for C H N SO (M )
8 15 2
87.0900, found: 187.0898.
3
1
1
.1.13. Compound 11c. Yield: 96% as thick oil; H NMR
4
(
300 MHz, D O): d 7.16 (d, 1H, JZ2.1 Hz), 7.13 (d, 1H,
2
JZ2.1 Hz), 3.95 (t, 2H, JZ6.9 Hz), 3.59 (s, 3H), 2.71

3394
X. He, T. H. Chan / Tetrahedron 62 (2006) 3389–3394
mechanical loss associated with the small scale experimen-
tal conditions.
6. Cossar, B. C.; Fournier, J. O.; Fields, D. L.; Reynolds, D. D.
J. Org. Chem. 1962, 27, 93.
7
. The sulfide 10 could also be made through the nucleophilic
replacement of the mesylate 5 with sodium thiomethoxide;
however, this approach was less desirable as the unpleasant
smelling methanethiol was inevitably generated in the workup.
Acknowledgements
We thank Merck Frosst Canada and Natural Science and
Engineering Research Council (NSERC) of Canada
for financial support. We also thank Dr. O. Mamer and
Dr. A. Lesimple for high-resolution mass spectrometric
analyses.
8. Miao, W.; Chan, T. H. Org. Lett. 2003, 5, 5003.
. Miao, W.; Chan, T. H. J. Org. Chem. 2005, 70, 3251.
9
1
1
0. He, X.; Chan, T. H. Synthesis, in press, 2006.
1. Visser, A. E.; Swatloski, R. P.; Reichert, W. M.; Mayton, R.;
Sheff, S.; Wierzbicki, A.; Davis, J. H.; Rogers, R. D., Jr.
Environ. Sci. Technol. 2002, 36, 2523–2529.
References and notes
1
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1
8. The sulfide 10b or 10c were recovered in 75–88% yield of the
sulfoxide used. The loss was attributed to mechanical loss
because of the small amount of sulfoxide used (0.9 mmol) and
the difficulty of complete recovery during transfer between
flasks.
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