Poly(ethylene) glycol as a green and reusable solvent in the oxidation of sulfides to sulfoxides using NaClO

Article abstract of DOI:10.1080/10426500903055204

This article describes selective oxidation of a range of sulfides to the corresponding sulfoxides in good yields by NaClO in poly(ethylene) glycol as a green and reusable solvent using sulfuric acid as an efficient acid catalyst. The new method compares favorably with previous methods in literature. A separable mixture of two new diastereoisomers is reported. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903055204

Phosphorus, Sulfur, and Silicon, 185:1381–1385, 2010
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Taylor & Francis Group, LLC
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ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903055204
POLY(ETHYLENE) GLYCOL AS A GREEN AND REUSABLE
SOLVENT IN THE OXIDATION OF SULFIDES TO
SULFOXIDES USING NaClO
Ali Amoozadeh and Firouzeh Nemati
Department of Chemistry, Faculty of Science, Semnan University, Semnan, Iran
This article describes selective oxidation of a range of sulfides to the corresponding sulfoxides
in good yields by NaClO in poly(ethylene) glycol as a green and reusable solvent using
sulfuric acid as an efficient acid catalyst. The new method compares favorably with previous
methods in literature. A separable mixture of two new diastereoisomers is reported.
Keywords Oxidation; poly(ethylene) glycol; sulfides, sulfoxides
INTRODUCTION
The search for new reaction media to replace volatile and often toxic solvents that are
used in organic synthetic procedures is an important objective of significant environmental
consequence. While the use of water as solvent is probably the most desirable approach,
this is often not possible due to the hydrophobic nature of the reactants and the sensitivity of
many catalysts to aqueous conditions. In this article, we describe the use of a widely avail-
able polymer, poly(ethylene) glycol (PEG 400), as nontoxic, inexpensive, and nonvolatile
solvent for the oxidation of sulfides to sulfoxides.
Organic sulfoxides are excellent synthons for a vast variety of transformations in
1
organic chemistry, such as C C bond formation, molecular rearrangement, and the prepa-
2
ration of biologically and medically important compounds. The first oxidation of sulfides
3
to sulfoxides was first described by Marker in 1865 using nitric acid.
Recently, oxidation sulfides to sulfoxides via various catalysts and oxidants, such as
4
5
6
Mn(III) complex, VO(acac)2, cis-[MoO2(phox)2]/UHP, immobilized cerium alkyl phos-
7
8
9
10
11
phonate, o-iodoxybenzoic acid, chromium(VI) oxide, TaCl5, Ce(IV) triflate, peroxo-
tungstate immobilizedon ionic liquid–modified silica, nitrophenyl-substituted polyperox-
otungstate catalyst, NaBO3.4H2O or Na2CO3.3H2O2/SSA/KBr, and tetrameric titanium
alkoxide/ionic liquid, are reported. Although a great number of new methods are available
for the conversion of sulfides to corresponding sulfoxides, different kinds of drawbacks
for those methods include use of metallic compounds, complex catalysts, or reagents; the
formation of sulfones as side products; and a longer reaction time commonly required.
12
13
14
15
Received 17 March 2009; accepted 20 May 2009.
We thank Semnan University for supporting this work.
Address correspondence to Ali Amoozadeh, Department of Chemistry, Faculty of Science, Semnan Univer-
sity, Semnan, Iran. E-mail: aliamoozadeh@yahoo.com
1
381

1382
A. AMOOZADEH AND F. NEMATI
Therefore, there still is a need for the development of new methods for this transformation,
as well as concern about all the above important protocols under the mild reaction condition.
It is further known that hypochlorous acid oxidation of certain sulfides leads to corre-
16
sponding sulfoxides, most probably via the corresponding chlorosulfonium ion as demon-
17
1c
strated by Johnson and McCants in the oxidation of thianes with tert-butyl hypochlorite. c
These types of oxidations are very much pH- and solvent-dependent, which also limits their
use.
RESULTS AND DISCUSSION
In continuation of our work on safe and environmentally friendly procedures for
preparation of chemical compounds,18 we decided to look at the use of poly(ethylene)
glycol as a reusable, inexpensive, nonvolatile, and commercially available solvent for the
selective oxidation of sulfides to sulfoxides. We used NaClO and H2SO4 as cheap and
commercially available reagents. The use of these cheap reagents and the environmentally
benign nature of PEG encouraged us to couple them together and study their utility for
oxidation of sulfides to sulfoxides.
To the best of our knowledge, there is no report in the literature on the selective oxi-
dation of sulfides to sulfoxides under these conditions. Oxidation of sulfides was performed
at room temperature in the presence of 4 mmol of sulfuric acid as catalyst and NaClO
(
(
1 mmol) 5.84% w/v as the oxidant in 4 mL polyethylene glycol as the solvent
Scheme 1).
O
NaClO (1 mmol.)
S
S
R1
R2
R1
R2
PEG, RT
H SO 4 mmol.
2
4
Scheme 1 Selective oxidation of sulfides to sulfoxides by NaClO in the presence sulfuric acid in poly(ethylene)
glycol as solvent.
In a typical general experimental procedure, a solution of sulfide and NaClO (both 1
mmol) in 4 mL of PEG in the presence of sulfuric acid (4 mmol) was stirred for 45–70 min,
resulting in the formation of the corresponding sulfoxides without any over oxidation and
with good to excellent yields. To study the scope of this procedure, a series of various
substituted sulfides including alkyl aryl sulfides and dialkyl sulfides was reacted according
to optimized reaction conditions. The results are summarized in Table I.
The process is devoid of sulfone formation, a byproduct common to most other
◦
peroxide-based oxidations even by warming the reaction mixture to 50 C. It is important
to note that some alpha hydroxyl phenylthio compounds, which have been successfully
1
8e,f
oxidized by this reagent in other solvents such as water and EtOH/water,
in these conditions.
did not work
In order to investigate the recyclability of poly(ethylene) glycol (it is immiscible
with ether), the oxidation product was extracted with it and the retained PEG phase was
reused. The solvent phase was recycled with a decrease in reactivity for three cycles, and
an approximately 5% weight loss of PEG was observed from each cycle.

OXIDATION OF SULFIDES TO SULFOXIDES USING PEG
1383
Table I Oxidation of sulfides to sulfoxides using NaClO in poly(ethylene) glycol/H2SO4 at room temperature
a
Yield (%) with H2SO4
Entry
R1
R2
Time (min)
as catalyst
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Et
Me
Et
Ph
Bn
Et
Me
n-Pr
n-Bu
55
45
60
70
60
65
70
60
70
75
80
85
90
80
72
75
78
Et
n-Pr
n-Bu
Ph
b
c
9
85
N
PG
PG= m-methoxybenzoyl
aIsolated yield.
b
The starting material was prepared according to ref. no. [19].
c
Two diastereoisomers were separated.
It is interesting to note (see Table I) that for protected 2-phenylthio dehydropiperidine
derivative (entry 9), two possible diastereoisomers were observed (Scheme 2). Note that the
19
20, 21
18e, f
sulfur atom is chiral. Based on the literature,
and based on our recent work,
as there
is no neighboring hydroxyl group to assist, both of sulfur’s electron pairs are available,
and the results are logical. Two mentioned diastereoisomers can be separated by flash
1
chromatography and characterized by spectroscopic methods (Scheme 2). The H NMR
spectrum shows clearly the difference between the two diastereoisomers. The less polar
diastereoisomer gives a triplet at 4.85 ppm integrating for one proton and corresponding
to the axial proton of C-6, and the corresponding peak for the more polar diatereoisomer
is a triplet at 4.75 ppm. The geminal protons of the phenylsulfinylmethyl for the less polar
diastereoisomer appear at 3.25 and 3.15 ppm in the form of doublets of doublets, while the
corresponding signals for more polar diastereoisomer appear at 3.40 and 3.20 ppm.
.
.
O
S
Ph
.
.
.
N
.
PG
NaClO (1 mmol.)
PEG, RT
S
Ph
N
.
.
O
2 4
H SO 4 mmol.
PG
S
PG= m-methoxybenzoyl
Ph
N
PG
Scheme 2 Two possible diastereoisomers for oxidation of protected 2-phenylthio dehydropiperidine.

1384
A. AMOOZADEH AND F. NEMATI
The less polar diastereoisomer has an Rf value of 0.39 (Et.:Hex., 90:10), and the most
polar diastereoisomer has an Rf value of 0.25 (Et.:Hex., 90:10).
In conclusion, a fast and exclusive generation of various sulfoxides from the cor-
responding sulfides was achieved using NaClO in polyethylene glycol as solvent in the
presence of H2SO4 as catalyst at room temperature. The reaction is highly selective and
efficient. The use of a reusable solvent, the exceptionally fast reaction rate, the absence of
a need for control of temperature, and no formation of over-oxidized products make this
protocol an attractive alternative to the existing methodologies.
EXPERIMENTAL
The IR spectra were taken on a Perkin-Elmer, model 783 spectrophotometer. The
NMR spectra have been recorded by a Bruker AMX-300 (300 MHz) spectrometer. The
chemical shifts are expressed in parts per million (ppm), and tetramethylsilane (TMS) was
used as internal reference. The mass spectra (MS) were recorded on an AEI MS-902 model.
General Procedure
A solution of sulfide (1 mmol) and diluted NaClO (1 mmol, 1.25 mL) (5.84% w/v)
in poly(ethylene) glycol (4 mL), and sulfuric acid (4 mmol) was stirred vigorously for an
appropriate time (45–70 min). After completion of the reaction (monitored by TLC), the
reaction mixture was cooled in a dry ice/acetone bath to precipitate the PEG 400 and organic
products extracted with ether. The ether layer was washed with water (2 mL) and dried over
MgSO4. The organic solvent was removed under reduced pressure to give the corresponding
pure sulfoxide (Table I). Two sulfoxides from entry 9 (Rf = 0.39; diethyl ether:hexane,
9
0:10) and (Rf = 0.25; diethyl ether:hexane, 90:10) were separated and purified by flash
chromatography as oily products. The recovered PEG 400 can be reused for three runs.
1
Known compounds were identified by IR and H NMR spectral data.
3-Isopropyl-5-phenylsulfinylmethyl-1,2-dehydro Piperidine
1
Less polar diastereoisomer. Rf: 0.39 (Et.:Hex., 90:10). H NMR (300 MHz,
CDCl3): δ 7.70 (dd, J = 8 and 2 Hz, 1H), 7.50 (m, 3H), 7.30 (t, J = 7 Hz, 1H), 7.00 (m, 3H),
6
3
.50 (d, J = 6 Hz, 1H), 5.05 (m, 1H), 4.85 (t, J = 4 Hz, 1H), 3.82 (s, 3H), 3.25 (dd, J = 7 and
Hz, 1H), 3.15 (dd, J = 7 and 4 Hz, 1H), 2.20 (m, 1H), 2.10 (m, 1H), 1.85 (m, 1H), 1.65
13
(
m, 1H) and 1.00 (dd, J = 9 and 6 Hz, 6H). C NMR (75 MHz, CDCl3): δ 169.3, 159.5,
1
3
6
44.4, 136.0, 131.1, 129.4, 129.3, 124.1, 119.2, 116.3, 113.3, 112.1, 61.9, 55.4, 47.9, 37.9,
2.7, 30.2 and 20.3. IR (neat): 3062, 2958, 2861, 1717, 1639, 1439, 1361, 1253, 1046, 749,
91 and 633 cm . MS (m/e): 398 (MH ); Calculated: 398.17899; Obtained: 398.17790.
−1
+
1
More polar diastereoisomer. Rf: 0.25 (Et.:Hex., 90:10). H NMR (300 MHz,
CDCl3): δ 7.70 (dd, J = 8 and 2 Hz, 1H), 7.50 (m, 3H), 7.30 (t, J = 7 Hz, 1H), 7.00 (m,
3
H), 6.50 (d, J = 6 Hz, 1H), 5.10 (dd, J = 6 and 2 Hz, 1H), 4.75 (t, J = 4 Hz, 1H), 3.83
(
2
s, 3H), 3.40 (dd, J = 7 and 3 Hz, 1H), 3.20 (dd, J = 7 and 4 Hz, 1H), 2.23 (m, 1H),
13
.10 (m, 1H), 1.85 (m, 1H), 1.65 (m, 1H) and 1.00 (dd, J = 9 and 5 Hz, 6H). C NMR
(75 MHz, CDCl3): δ 169.3, 159.5, 144.4, 136.0, 131.1, 129.4, 129.3, 124.1, 119.2, 116.3,
1
1
3
13.3, 112.1, 61.9, 55.4, 47.9, 37.9, 32.1, 30.2 and 20.3. IR (neat): 3060, 2955, 2860, 1715,
640, 1440, 1360, 1250, 1045, 750, 690 and 630 cm . MS (m/e): 398 (MH ); Calculated:
98.17899; Obtained: 398.17830.
−1
+

OXIDATION OF SULFIDES TO SULFOXIDES USING PEG
1385
REFERENCES
1
. (a) M. C. Careno, M. Ribagorda, and G. H. Poster, Angew. Chem. Int. Ed., 41, 2753 (2002);
b) J. P. Marino, M. S. Mcclure, D. P. Holub, J. V. Comasseto, and F. C. Tucci, J. Am. Chem. Soc.,
24, 1664 (2002); (c) M. R. Acocella, M. A. De Rosa Massa, L. Palombi, R. Villano, and A.
(
1
Scettri, Tetrahedron, 61, 4091 (2005); (d) A. Massa, A. V. Malkov, and P. Kocovsky, Tetrahedron
Lett., 42, 7147 (2001).
2
3
4
5
6
. B. M. Trost, Chem. Rev., 78, 363 (1978).
. M. Madesclaire, Tetrahedron, 42, 5459 (1986).
. F. Hosseinpoor and H. Golchoubian, Tetrahedron Lett., 47, 5195 (2006).
. K. L. Prasanth and H. Maheswaran, J. Mol. Catal. A: Chem., 268, 45 (2007).
. M. Bagherzadeh, L. Tahsini, R. Latifi, A. Ellern, and L. K. Woo, Inorg. Chim. Acta, 361, 2019
(2008).
7. M. Al-Hashimi, G. Roy, A. C. Sullivan, and J. R. H. Wilson, Tetrahedron Lett., 46, 4365 (2005).
8. V. G. Shukla, P. D. Salgaonkar, and K. G. Akamanchi, J. Org. Chem., 68, 5422 (2003).
9. L. Xu, J. Cheng, and M. L. Trudell, J. Org. Chem., 68, 5388 (2003).
1
1
0. M. Kirihara, J. Yamamoto, T. Noguchi, and Y. Hirai, Tetrahedron Lett., 50, 1180 (2009).
1. B. Rama Raju, S. Sarkar, U. Ch. Reddy, and A. K. Saikia, J. Mol. Catal. A: Chem., 308, 169
(2009).
1
1
1
2. X.-Y. Shi and J.-F. Wei, J. Mol. Catal. A: Chem., 280, 142 (2009).
3. A. M. Al-Ajlouni, T. M. Daiafla, and M. El-Khateeb, J. Mol. Catal. A: Chem., 275, 139 (2007).
4. D. Habibi, M. A. Zolfigol, M. Safaiee, A. Shamsian, and A. Ghorbani-Choghamarani, Catal.
Commun., 10, 1257 (2009).
15. Ch. V. Reddy and J. G. Verkade, J. Mol. Catal. A: Chem., 272, 233 (2007).
1
6. L. S. S. R e´ amonn and W. I. O’Sullivan, J. Chem. Soc., Chem. Commun., 1012 (1976).
17. (a) C. R. Johnson and D. McCants Jr., J. Am. Chem. Soc., 87, 1109 (1965); (b) C. R. Johnson
and J. J. Rigau, J. Am. Chem. Soc., 91, 5398 (1969).
18. (a) M. A. Bigdeli, F. Nemati, and G. H. Mahdavinia, Tetrahedron Lett., 48, 6801 (2007);
(
(
b) M. A. Bigdeli, M. M. Heravi, and F. Nemati, Synth. Commun., 37, 2225 (2007);
c) M. A. Bigdeli, H. Dostmohammadi, G. H. Mahdavinia, and F. Nemati, J. Heterocycl. Chem.,
45, 1203 (2008) (d) M. A. Bigdeli, M. M. Heravi, F. Nemati, and G. H. Mahdavinia, Arkivoc,
243 (2008) (e) A. Amoozadeh and F. Nemati, S. Afr. J. Chem., 62, 44 (2009); (f) A. Amoozadeh
and F. Nemati, Phosphorus, Sulfur, and Silicon, 184, 2569 (2009).
1
2
9. D. Gravel, A. Amoozadeh, and Y. Wang, Tetrahedron Lett., 39, 8039 (1998).
0. O. De Lucchi, V. Lucchini, C. Marchioro, G. Valle, and G. Modena, J. Org. Chem., 51, 1457
(1986).
2
1. A. Hirschon, J. Takahashi Doi, and W. K. Musker, J. Am. Chem. Soc., 104, 725 (1982).