Efficient and selective sulfoxidation by hydrogen peroxide, using a recyclable flavin-[BMIm]PF6 catalytic system

Article abstract of DOI:10.1021/jo060274q

A new flavin catalyst 2 immobilized in an ionic liquid ([BMIm]PF ₆) was used for the highly selective oxidation of sulfides to sulfoxides by hydrogen peroxide. The sulfoxides were obtained in good to high yields and high selectivity without any

Full text of DOI:10.1021/jo060274q

Efficient and Selective Sulfoxidation by Hydrogen Peroxide, Using a
Recyclable Flavin-[BMIm]PF6 Catalytic System
Auri A. Linde´n, Mikael Johansson, Nina Hermanns, and Jan-E. Ba¨ckvall*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm UniVersity,
SE-106 91 Stockholm, Sweden
jeb@organ.su.se
ReceiVed February 9, 2006
A new flavin catalyst 2 immobilized in an ionic liquid ([BMIm]PF6) was used for the highly selective
oxidation of sulfides to sulfoxides by hydrogen peroxide. The sulfoxides were obtained in good to high
yields and high selectivity without any detectable overoxidation to sulfone. The catalyst in the ionic
liquid was recycled up to seven times without loss of activity or selectivity.
Introduction
dihydroxylation of olefins.8 The effect of substituents on the
oxidation potential of the flavin has been recently reported by
us.9
There are a number of ways to reuse a catalyst and a common
way is to immobilize it on a solid support.10,11 Some recent
approaches involve anchoring the catalyst via a tether to a solid
surface.11 This requires tedious synthetic work and it is often
difficult to quantify the amount of catalyst on the surface. Ionic
Organosulfur compounds are important synthetic intermedi-
ates and they occur in a variety of pharmaceuticals. Furthermore,
enantiomerically pure sulfoxides are often used as chiral ligands
and auxiliaries in asymmetric synthesis.1,2 Because of the interest
in sulfoxides there is an increasing demand of selective and
efficient methods for their preparation.3
There are a number of methods available for the preparation
of sulfoxides; however, many of these are associated with low
selectivity.3 We have previously reported on a highly chemose-
lective oxidation of sulfides by H2O2 using flavin 1 as catalyst
both for simple sulfides4 and for allylic sulfides.5,6 The same
flavin was also utilized as an efficient catalyst for the oxidation
of amines to amine oxides7 and this made possible an in situ
reoxidation of NMM (N-methylmorpholine) to NMO (N-
methylmorpholine N-oxide) in a H2O2-based osmium-catalyzed
(4) (a) Minidis, A. B. E.; Ba¨ckvall, J.-E. Chem. Eur. J. 2001, 7, 297-
302. (b) For a related H2O2-based sulfoxidation catalyzed by a flavin see
ref 4c. (c) Murahashi, S. I.; Oda, T.; Masui, Y. J. Am. Chem. Soc. 1989,
111, 5002-5003.
(5) Linde´n, A. A.; Kru¨ger, L.; Ba¨ckvall, J.-E. J. Org. Chem. 2003, 68,
5890-5896.
(6) For a related flavin-catalyzed oxidation of sulfides with molecular
oxygen see: Imada, Y.; Iida, H.; Ono, S.; Murahashi, S.-I J. Am. Chem.
Soc. 2003, 125, 2868-2869.
(7) (a) Bergstad, K.; Ba¨ckvall, J.-E. J. Org. Chem. 1998, 63, 6650-
6655. (b) For a H2O2-based oxidation of secondary amines to nitrones
catalyzed by a flavin see ref 4c.
(1) (a) Carren˜o, M. C. Chem. ReV. 1995, 95, 1717-1760. (b) Ferna´ndez,
I.; Khiar, N. Chem. ReV. 2003, 103, 3651-3705.
(8) (a) Bergstad, K.; Jonsson, S. Y.; Ba¨ckvall, J.-E. J. Am. Chem. Soc.
1999, 121, 10424-10425. (b) Bergstad, K.; Piet, J. J. N.; Ba¨ckvall, J.-E. J.
Org. Chem. 1999, 64, 2545-2548. (c) Jonsson, S. Y.; Adolfsson, H.;
Ba¨ckvall, J.-E. Chem. Eur. J. 2003, 9, 2783-2788. (d) Jonsson, S. Y.;
Adolfsson, H.; Ba¨ckvall, J.-E. Org. Lett. 2001, 3, 3463-3466. (e) Jonsson,
S. Y.; Fa¨rnegårdh, K.; Ba¨ckvall, J.-E. J. Am. Chem. Soc. 2001, 123, 1365-
1371.
(2) (a) Grennberg, H.; Gogoll, A.; Ba¨ckvall, J.-E. J. Org. Chem. 1991,
56, 5808-5811. (b) Petra, D. G. I.; Kamer, P. C. J.; Spek, A. L.;
Schoemaker, H. E.; van Leeuwen, P. W. N. M. J. Org. Chem. 2000, 65,
3010-3017. (c) Brebion, F.; Delouvrie, B.; Najera, F.; Fensterbank, L.;
Malacria, M.; Vaissermann, J. Angew. Chem., Int. Ed. 2003, 42, 5342-
5345. (d) Chen, M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126, 1346-
1347.
(9) Linde´n, A. A.; Hermanns, N.; Ott, S.; Kru¨ger, L.; Ba¨ckvall, J.-E.
Chem. Eur. J. 2005, 11, 112-119.
(3) (a) Ba¨ckvall, J.-E. In Modern Oxidation Methods; Ba¨ckvall, J.-E.,
Ed.; Wiley-VCH: Weinheim, Germany, 2004; pp 193-222. (b) Legros,
J.; Bolm, C. Chem. Eur. J. 2005, 11, 1086-1092 and references cited
therein.
(10) (a) Bolm C.; Gerlach, A. Eur. J. Org. Chem. 1956, 21, 1-27. (b)
Thomas, J. M.; Raja, R. J. Organomet. Chem. 2004, 689, 4110-4124.
(11) Kirschning, A. Immobilized Catalysts. In Top. Curr. Chem. 2004,
242.
10.1021/jo060274q CCC: $33.50 © 2006 American Chemical Society
Published on Web 04/21/2006
J. Org. Chem. 2006, 71, 3849-3853
3849

Linde´n et al.
FIGURE 2. The ionic liquid.
FIGURE 1. Flavins 1 and 2.
and 8-regioisomers. In this step also the acid moiety was
methylated to give the ester. The ester was hydrolyzed by
reaction with concentrated hydrochloric acid, which afforded
flavin 7 in 85% yield in a 3:2 ratio of the 7- and 8-regioisomers.
The precatalyst 2 was obtained in 67% yield by reductive
alkylation of 7.
SCHEME 1. Synthesis of the Catalyst
Our previous studies on the substituent effects have shown
that electron-withdrawing substituents on the flavin increase its
oxidation potential and hence the rate of the corresponding
flavin-catalyzed oxidation.9 Thus, flavin 2 is expected to give
a faster sulfoxidation with H2O2 compared to 1. Furthermore,
and more importantly, the carboxylate group makes an im-
mobilization of 2 in an ionic liquid very efficient. Flavin 2 is
most likely present in its zwitterionic form or as its carboxylate
ion. The 1H NMR spectrum of 2 is consitent with a zwitterionic
form with the nitrogen in the 5-position protonated since in both
isomers the two hydrogens of the CH2 group in the ethyl group
on N-5 are coupled with an additional proton. Furthermore, the
1H NMR shows that the two protons in the CH2 group are
nonequivalent and appear at different shifts (∆δ ) 0.48 ppm;
see the Experimental Section). In previous studies we have used
flavin 1 in ionic liquid [BMIm]PF6 for the recycling of NMM
to NMO in the osmium-catalyzed dihydroxylation.18 One
problem with flavin 1 is that it leaches on recycling and attempts
to immoblize 1 in [BMIm]PF6 for sulfoxidation by H2O2 were
unsuccessful due to severe leaching.17 p-Tolyl methyl sulfide
(8a) was used as a model substrate in the tuning of reaction
conditions. We found that sulfide 8a was efficiently oxidized
to sulfoxide 8b using 2 mol % of flavin 2 and 1.5 equiv of
H2O2 in the ionic liquid [BMIm]PF6/methanol mixture. The
immobilized catalytic system showed high activity and no
overoxidation was detected. The new system was applied to
several other sulfides and the results are presented in Table 1.
The sulfides were oxidized to sulfoxides by H2O2 in high
yields at room temperature with short reaction times (Scheme
2). In all cases a high selectivity for sulfoxide was obtained
with no overoxidation to sulfone. The system tolerates both
electron-rich and electron-deficient substrates, although electron-
deficient sulfides required slightly longer reaction times. The
electron-rich sulfides 8a-10a gave the corresponding sulfoxides
8b-10b, respectively, within 3 h in good to excellent yields
(Table 1, entries 1-3). The electron-deficient p-bromophenyl
methyl sulfide 11a yielded 83% of the sulfoxide 11b in 5 h
(Table 1, entry 4). The electronic properties do not explain why
naphthyl sulfide 12a required about 3 times longer reaction time
to be oxidized than the corresponding tolyl derivative 8a (Table
1, entry 5 vs entry 1). We observed that the starting sulfide
12a was poorly soluble in the reaction medium, and this may
explain the slightly longer reaction time. The more sterically
hindered sulfide 13a-15a afforded the corresponding sulfoxides
13b-15b in good yields within 4.5 h (Table 1, entries 6-8).
To investigate the chemoselectivity of the new catalytic
system a few allylic sulfides were tested. The system is
compatible with allylic sulfides 17a-21a leaving the double
liquids have attracted considerable attention in recent years as
good and reusable reaction media for organic reactions.12 The
reusability arises from the fact that ionic liquids have essentially
no vapor pressure and that they are easily extractable. They are
generally good solvents for organic compounds as well as for
a wide range of inorganic complexes such as metal catalysts.13
Many reactions have been reported utilizing ionic liquids as
solvents, and among them one finds examples of metal
catalysis,12,14 as well as bio- and organocatalysis.12 So far only
two groups have reported on the oxidation of sulfides to
sulfoxides in ionic liquid.15,16
Attempts to immobilize flavin 1 in an ionic liquid for
sulfoxidation and recycling gave poor results.17 In this work
we have prepared the new flavin 2 and report on its use as an
ionic liquid-immobilized catalyst for the highly selective H2O2
oxidation of sulfides to sulfoxides. An important feature of this
system is that it can be recycled many times without any
detectable loss of activity.
Results and Discussion
Flavin 2 was synthesized from 3,4-diaminobenzoic acid (3)
and alloxane monohydrate (4) in good yield according to
standard procedures (Scheme 1).9 The first step afforded flavin
5 in quantitative yield, in 1:1 ratio of the 7- and 8-hydroxycar-
bonyl regioisomers, and was subsequently methylated by methyl
iodide to form flavin 6 in 86% yield, in a 3:2 ratio of the 7-
(12) Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S. Tetrahedron
2005, 61, 1015-1060.
(13) Chiappe, C.; Pieraccini, D. J. Phys. Org. Chem. 2005, 18, 275-
297.
(14) Special Issue on Organometallic Chemistry in Ionic Liquids;
Ba¨ckvall, J. E., Adams, R. D., Eds. J. Organomet. Chem. 2005, 690 (15).
(15) (a) Cimpeanu, V.; Parvulescu, V. I.; Amoro´s, P.; Beltra´n, D.;
Thompson, J. M.; Hardacre, C. Chem. Eur. J. 2004, 10, 4640-4646. (b)
Cimpeanu, V.; Parvulescu, A. N.; Parvulescu, V. I.; On, D. T.; Kaliaguine,
S.; Thompson, J. M.; Hardacre, C. J. Catal. 2005, 232, 60-67.
(16) Okrasa, K.; Guibe-Jampel, E.; Therisod, M. Tetrahedron: Asymmetry
2003, 14, 2487-2490.
(17) Recycling experiments with catalyst 1 in [BMIm]PF6 for sulfoxi-
dation of 8a and 12a with H2O2 gave poor results (% yield of sulfoxide);
run 1 91-99%, run 2 55-60%, run 3 40-50%.
(18) Closson, A.; Johansson, M.; Ba¨ckvall, J.-E. Chem. Commun. 2004,
1494-1495.
3850 J. Org. Chem., Vol. 71, No. 10, 2006

SelectiVe Sulfoxidation by Hydrogen Peroxide
TABLE 1. Oxidation of Sulfides by Hydrogen Peroxide in
[BMIm]PF6/MeOH with Use of 2 mol % of 2a
FIGURE 3. The amount of sulfoxide 8b with and without precatalyst
2 present.
SCHEME 3. General Reaction Procedure for the Recycling
Experiments
TABLE 2. Recycling of the Flavin Catalyst in Ionic Liquida,b
yieldc (%)
substrate/
entry
product
run 1 run 2 run 3 run 4 run 5 run 6/7
1
8a/8b
9a/9b
10a/10b
18a/18b
78
87e
95
91
84
87e
98
94
80
87e
89
88
88
87e
86
-
91
87e
92
-
89/-
87e/88
94/-
-/-
2d
3
4
a Unless otherwise noted the reactions were run with use of 1 mmol of
sulfide in 0.5 mL of [BMIm]PF6 and 3.2 mL of MeOH. Flavin 2 (6.3 mg,
2 mol %) and H2O2 (150-170 µL, ∼1.5 equiv) were added and the reaction
was stirred for 1.5-2.5 h. b Conversion determined by 1H NMR, 96-99%.
c Isolated yield. d A seventh run gave 88% yield. e The crude products of
runs 1-6 were combined to give 482% isolated yield converted on one
run, which gives in average 87% yield per run.
stopped at 86% conversion, which is higher than that with the
previous method,5 and the product 22b was isolated in 66%
yield.
Even though the conversions are above 95% in most of the
cases the isolated yields are lower for the more polar substrates.
This is due to the fact that the sulfoxides formed are not fully
extracted out of the ionic liquid.
a Unless otherwise noted the reactions were run with 1 mmol of sulfide
in 0.5 mL of [BMIm]PF6 and 3.2 mL of MeOH. Flavin 2 (6.3 mg, 2 mol
%) and H2O2 (150-170 µL, ∼1.5 equiv) were added and the reaction
mixture was stirred for the given time. b Isolated yields unless otherwise
noted. c Diastereomeric ratio 4:1. d NMR yield.
SCHEME 2. General Reaction Procedure for the
Sulfoxidation
The background reactions (in the absence of flavin 2) were
negligible for all sulfides within the reaction time and for the
oxidation of methyl p-tolyl sulfide the reaction was monitored
with GC both with and without catalyst 2. The results are
presented in Figure 3. The recycling of catalyst 2 is highly
efficient and was demonstrated with four different sulfoxidations
(Scheme 3, Table 2). The reactions were run as above but now
the cosolvent methanol was evaporated after completion of the
reaction and the residual ionic liquid phase was extracted 3 times
with 10 mL of diethyl ether. The remaining H2O2 in the ethereal
phase was quenched with sodium dithionite and the ether phase
bond untouched (Table 1, entries 10-14). The sulfoxides 17b-
21b were formed in good to excellent yield within 4.5 h. The
diphenyl sulfide (16a) and propargyl phenyl sulfide (22a) (Table
1, entries 9 and 15) gave the lowest yields. The reaction of 22a
J. Org. Chem, Vol. 71, No. 10, 2006 3851

Linde´n et al.
1H NMR (400 MHz, CDCl3) δ 8.92 (d, J ) 1.8 Hz, 1H), 8.38 (dd,
J ) 1.9, 8.9 Hz, 1H), 7.98 (d, J ) 8.9 Hz), 3.97 (s, 3H), 3.78 (s,
3H), 3.56 (s, 3H). 13C NMR (CDCl3, 100 MHz) for the mixture δ
165.7, 159.4, 159.3, 150.5, 146.4, 145.9, 145.3, 142.6, 141.5, 138.9,
134.5, 133.3, 133.2, 131.1, 131.0, 130.7, 130.5, 130.2, 128.4, 128.1,
53.0, 52.9, 29.8, 29.8, 29.4, 29.4.
was washed with 10 mL of water.19 The water phase was
subsequently extracted 3 times with 10 mL of diethyl ether. It
was demonstrated that the ionic liquid-catalyst system can be
recycled up to 7 times for the p-methoxyphenyl methyl sulfide
(9b) without significant loss of either activity or selectivity. The
results are given in Table 2.
Synthesis of N1,N3-dimethyl-7/8-hydroxycarbonyl alloxazine
(7). The N1,N3-dimethyl-7/8-methoxycarbonyl alloxazine (6) (1
mmol, 300 mg) was suspended in concentrated hydrochloric acid
(4 mL) and the mixture was heated at 80 °C for 22 h. The reaction
mixture was allowed to cool to room temperature and poured into
12 mL of ice-water. The formed precipitate was filtered off and
washed with water and small amounts of diethyl ether and dried
under vacuum. The product was obtained as a yellow solid in 85%
yield as a 3:2 mixture of the 7- and 8-regioisomer. Major product
7-hydroxycarbonyl derivative: 1H NMR (400 MHz, DMSO-d6):
δ ) 8.49 (d, 1.7, 1H), 8.31 (d, J ) 8.7 Hz, 1H), 8.21 (dd, J ) 1.8,
8.7 Hz, 1H), 3.65 (s, 3H), 3.39 (s, 3H). Minor product 8-hy-
droxycarbonyl derivative: 1H NMR (400 MHz, DMSO-d6): δ )
8.67 (d, 1.7, 1H), 8.36 (dd, J ) 1.8, 8.7 Hz, 1H), 8.08 (d, J ) 8.7
Hz, 1H), 3.65 (s, 3H), 3.39 (s, 3H).
Synthesis of Dihydroflavin 2. N1,N3-Dimethyl-7/8-hydroxy-
carbonylalloxazine (7) (0.421 g, 1.5 mmol) was suspended in a
mixture of degassed ethanol (25 mL) and water (20 mL). Palladium
(10%) on charcoal (0.162 g, preactivated under vacuum) was added
followed by hydrochloric acid (3.2 mL) and acetaldehyde (3.2 mL).
The reaction was stirred overnight under 30 psi of H2 (g). After 26
h the reaction mixture was filtered through a Celite plug, in a
Schlenk equipped with a frit, which was connected to a Schlenk.
The Celite was washed with degassed ethanol until all yellow
substance was removed from the Celite plug. The Schlenk frit was
then replaced with a tube connected to a cold trap and the solvents
were removed under vacuum. The residual solids were suspended
in water and filtered in another Schlenk frit after which they were
left to dry over P2O5. Product 2 was obtained as an orange-red
powder in 67% yield. MS (MALDI-TOF) m/z calcd for C15H16N4O4
[M]+ 316.31, found 316.27. Major product 7-hydroxycarbonyl
derivative:1H NMR (400 MHz, CD3OD) δ 7.94 (d, J ) 2.0 Hz,
1H), 7.88 (dd, J ) 2.1, 8.9 Hz, 1H), 7.08 (d, J ) 8.8 Hz, 1H), 4.11
(m, J ) 2.6, 7.2, 14.6 Hz, 1H), 3.63 (m, J ) 6.6, 6.6, 14.6 Hz,
1H), 3.52 (s, 3H), 3.25 (s, 3H), 1.53 (t, J ) 6.9 Hz, 3H). Minor
product 8-hydroxycarbonyl derivative: 1H NMR (400 MHz, CD3-
OD) δ 7.70 (d, J ) 1.0 Hz, 1H), 7.51 (dd, J ) 1.3, 8.1 Hz, 1H),
7.34 (d, J ) 8.1 Hz, 1H), 4.11 (m, J ) 2.6, 7.2, 14.6 Hz, 1H), 3.63
(m, J ) 6.6, 6.6, 14.6 Hz, 1H), 3.52 (s, 3H), 3.26 (s, 3H), 1.55 (t,
J ) 6.9 Hz, 3H).
General Procedure for the Sulfoxidation. The catalyst precur-
sor 2 (6.3 mg, 0.02 mmol) was dissolved in [BMIm]PF6 (0.5 mL)
and methanol (3.2 mL) in a 20 mL vial. The sulfide (1 mmol) was
then added followed by hydrogen peroxide (30% in water) (170
µL). The reactions were stirred for the given time (the reactions
were followed by TLC) after which the methanol was removed
and the residual ionic liquid was extracted with diethyl ether (3 ×
15 mL). The combined ether layers were treated with sodium
dithionite and washed with water (3 × 10 mL). The ether phase
was dried over Na2SO4, filtered, and concentrated in vacuo. The
products were purified by conventional or Biotage flash chroma-
tography.
p-Tolyl Methyl Sulfoxide (8b). Isolated yield after 1 h of
reaction time, 78%. The NMR data were in accordance with those
previously reported.4 The conversions (Figure 3) were determined
by GC analysis of the reaction mixture: tR(p-tolyl methyl sulfide)
) 12.7 min; tR(p-tolyl methyl sulfoxide) ) 17.2 min.
As is clear from the recycling experiments, the catalyst stays
in the ionic liquid and no detectable leaching of the catalyst
takes place. The system is equally active in the seventh run as
in the first run. It is important to note that the catalyst system
could be stored in the freezer for days between the runs with
neither decomposition nor loss of activity of the catalyst. This
is noteworthy since the flavin catalysts are usually sensitive
toward autooxidative degradation in solution.
In conclusion, we have developed a mild and robust catalytic
system for sulfoxidation. The combination of an electron-
deficient flavin catalyst with the use of an ionic liquid as medium
leads to an efficient and stable system. We have shown that a
variety of sulfides can be selectively oxidized to sulfoxides in
good yields. It was demonstrated that the catalyst in the ionic
liquid can be recycled up to seven times. The selectivity and
yield did not decrease on recycling, and the only product
obtained was the desired sulfoxide. The efficient immobilization
of flavin 2 is most likely due to it being present as its zwitterion
form and therefore it is not extracted by ether.
Experimental Section
Synthesis of 7/8-Hydroxycarbonylalloxazine (5). To a stirred
solution of 3,4-diaminobenzoic acid (3, 3.04 g, 20 mmol) in 170
mL of acetic acid were added boric acid (1.36 g, 22 mmol) and
alloxane (4) monohydrate (3.36 g, 21 mmol). The reaction was
stirred for 3 h at room temperature after which the precipitated
product was filtered off and washed, first with acetic acid then with
diethyl ether, water, and last diethyl ether. The product 5 (green
powder) was isolated in a 3:2 ratio of the 7- and 8-isomer in
1
quantitative yield. Major isomer: H NMR (400 MHz, DMSO-
d6) δ 12.02 (s, 1H), 11.79 (s, 1H), 8.29 (d, J ) 1.9 Hz, 1H), 8.18
(d, J ) 8.8 Hz, 1H), 8.09 (dd, J ) 1.9, 8.8 Hz, 1H). Minor isomer:
1H NMR (400 MHz, DMSO-d6) δ 12.06 (s, 1H), 11.80 (s, 1H),
8.55 (d, J ) 2.0 Hz), 8.25 (dd, J ) 2.0, 8.8 Hz, 1H), 7.90 (d, J )
8.8 Hz, 1H). 13C NMR (DMSO-d6, 100 MHz) for the mixture δ
167.0, 167.0, 160.8, 160.8, 150.7, 150.7, 148.6, 148.1, 145.4, 142.5,
141.4, 138.8, 135.1, 134.0, 133.7, 132.8, 132.5, 131.1, 130.8, 129.1,
128.0, 127.9.
Synthesis of N1,N3-Dimethyl-7/8-methoxycarbonylalloxazine
(6).9 To a stirred solution of 7/8-hydroxycarbonylalloxazine (5)
(2.58 g, 10 mmol) in 500 mL of dimethylformamide (DMF) were
added potassium carbonate (K2CO3) (4.70 g, 34 mmol) and methyl
iodide (2 mL, 32 mmol). The reaction mixture was stirred overnight
(22 h) after which it was filtered through a glass filter funnel to
remove inorganic salts. The liquids were collected and the solvents
removed under reduced pressure. The solids were then suspended
in 500 mL of chloroform (CHCl3) and extracted with 200 mL of 2
M hydrochloric acid (HCl), 200 mL of diluted brine, and finally
200 mL of brine. The organic phase was dried over sodium sulfate
(Na2SO4) and after filtration the solvents were removed and the
product dried under vacuum. The product 6 was isolated in 86%
yield as a yellow solid. The product was a mixture of the
7-methoxycarbonyl derivative and the 8-methoxycarbonyl derivative
in a 3:2 ratio. Major isomer: 1H NMR (400 MHz, CDCl3) δ 8.62
(d, J ) 1.7 Hz, 1H), 8.29 (d, J ) 8.9 Hz, 1H), 8.23 (dd, J ) 1.7,
8.9 Hz, 1H), 3.99 (s, 3H), 3.78 (s, 3H), 3.56 (s, 3H). Minor isomer:
General Procedure for the Recycling of the Ionic Liquid-
Catalyst System. The catalyst precursor 2 (6.3 mg, 0.02 mmol)
was dissolved in [BMIm]PF6 (0.5 mL) and methanol (3.2 mL) in
a 20 mL vial. The sulfide (1 mmol) was then added followed by
hydrogen peroxide (170 µL). The reaction was stirred for the given
(19) It is important that no hydrogen peroxide is left in the ether phase
since it causes overoxidation after removal of the solvent.
3852 J. Org. Chem., Vol. 71, No. 10, 2006

SelectiVe Sulfoxidation by Hydrogen Peroxide
time (the reaction was followed by TLC) after which the methanol
was removed and the residual ionic liquid was extracted with diethyl
ether (3 × 15 mL). The combined ether layers were treated with
sodium dithionite and washed with water (10 mL). The water phase
was back extracted with diethyl ether (3 × 10 mL). The combined
ether phases were dried over Na2SO4, filtered, and concentrated in
vacuo. The products were isolated by flash chromatography. The
ionic liquid phase was reused after evaporation of the remaining
diethyl ether. Sulfide (1 mmol) and H2O2 (1.5 equiv) were added
after addition of methanol (3.2 mL).
Acknowledgment. This research was supported by the
Swedish Research Council (VR) and Deutscher Akademischer
Austauschdienst (DAAD).
Supporting Information Available: General experimental and
characterization of compounds 9b-22b; copies of NMR spectra
of compounds 2, 5-7, 10b, 13b, 14b, 15b, 16b, and 21b. This
material is available free of charge via the Internet at http://
pubs.acs.org.
JO060274Q
J. Org. Chem, Vol. 71, No. 10, 2006 3853