Heterocyclic amine salts of Keggin heteropolyacids used as catalyst for the selective oxidation of sulfides to sulfoxides

Article abstract of DOI:10.1016/j.tetlet.2008.01.009

A range of sulfides can be selectively oxidized to the corresponding sulfoxides in good yields using catalytic quantities of heterocyclic amine salts (quinoline, cinchonine, and cinchonidine) of Keggin heteropolyacids with different green oxidants. The cinchonine heteropolyacid catalyst is easily recoverable and reusable without loss of its catalytic activity, and an enantiomeric excess can be obtained.

Full text of DOI:10.1016/j.tetlet.2008.01.009

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1441–1444
Heterocyclic amine salts of Keggin heteropolyacids used as
catalyst for the selective oxidation of sulfides to sulfoxides
*
´
Angel G. Sathicq, Gustavo P. Romanelli , Valeria Palermo, Patricia G. Vazquez,
Horacio J. Thomas
Centro de Investigacio´n y Desarrollo en Ciencias Aplicadas ‘Dr. Jorge J. Ronco’ (CINDECA), Departamento de Quı´mica,
Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 N° 257 (B1900AJK) La Plata, Argentina
Received 12 December 2007; revised 28 December 2007; accepted 3 January 2008
Available online 8 January 2008
Abstract
A range of sulfides can be selectively oxidized to the corresponding sulfoxides in good yields using catalytic quantities of heterocyclic
amine salts (quinoline, cinchonine, and cinchonidine) of Keggin heteropolyacids with different green oxidants. The cinchonine hetero-
polyacid catalyst is easily recoverable and reusable without loss of its catalytic activity, and an enantiomeric excess can be obtained.
Ó 2008 Elsevier Ltd. All rights reserved.
Heteropolyacid compounds (HPAs) with Keggin-struc-
ture are polynuclear complexes principally constituted by
molybdenum or tungsten as polyatoms, and phosphorus
and silicon as central atoms or heteroatoms. They operate
either as multielectron oxidants or strong acids, with an
acid strength higher than that of classical acids. The list
of liquid-phase reactions in which HPAs may be used to
replace the conventional inorganic and organic acids is
extensive. They are used as industrial catalysts for several
liquid-phase reactions.1–5
We have recently reported a range of heteropolyacids
with Keggin-type structure for performing acidic catalysis
and oxidation reactions such as the tetrahydropyranylation
of phenols and alcohols,6–8 chromone and flavone prepara-
tion,9 ethyl b-arylaminocrotonates,10 and the phenol,11 sulf-
ide,12 alcohol, and amine oxidations.13 The pyridinium
salts of Keggin-type molybdovanadophosphates are appro-
priate catalysts to perform the selective oxidation of sulf-
ides to sulfoxides with hydrogen peroxide.14
oxides are important in organic synthesis as an activating
group, they have been utilized extensively in carbon
bond-forming reactions,15 as building blocks, especially
as chiral auxiliaries,16 and they play key roles in the activa-
tion of enzymes.17
There are several reagents available for these key trans-
formation; they are conventionally achieved using stoichio-
metric amounts of both organic and inorganic reagents, for
example, nitric acid, chromic acid, manganese dioxide,
ozone, sodium periodate, selenium dioxide, hypervalent
iodine reagents, sodium perborate,18 halogens, tetrabutyl-
ammonium peroxydisulfate,19 binuclear manganese
complex-periodic acid,20 N-hydroxyphalimide-molecular
oxygen,21 and FeBr3–nitric acid.22
During the last years, very useful procedures involving
catalysis and hydrogen peroxide as oxidant, for example,
H2WO4, H3PW12O40 + [(C8H17)4N]Br, rhenium(V) oxo
phosphine complexes, methyltrioxorhenium, Sc(OTf)3,
(salen) Mn(III), and Ti(IV) complexes, tellurium dioxide
and TPPFe(III)Cl-imidazole have been used.21 They have
been developed to promote the oxidation of organic sub-
strates due to their effective oxygen content, low cost,
and safety in storage and operation.23,24 Other green oxi-
dants such as urea–hydrogen peroxide complex,25 sodium
percarbonate,26 and tert-butyl-hydroperoxide23 have been
On the other hand, the selective oxidation of sulfides to
sulfoxides is of interest because of the importance of sulf-
oxides as synthetic intermediates in organic synthesis. Sulf-
*
Corresponding author. Tel.: +54 221 421 1353.
E-mail address: gpr@quimica.unlp.edu.ar (G. P. Romanelli).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.009

1442
A. G. Sathicq et al. / Tetrahedron Letters 49 (2008) 1441–1444
to sulfone results. For example, at 50 °C and for 3 h, a 99%
O
S
selectivity to sulfone is achieved (Table 1, entry 4).
The catalytic activity of some amine salts of Keggin-type
heteropolyacids in the selective oxidation of sulfides to sulf-
oxides with hydrogen peroxide is reported in Table 1,
entries 5–7. When PM12Cin was used, the catalytic activity
decreased, but these catalysts have the advantage on being
insoluble in the mixture reaction. When PM12Cin is used as
catalyst, a conversion of 100% is observed at 15 h of reac-
tion, with 95% selectivity to sulfoxide (Table 1, entry 7).
The replacement of acetonitrile by a green solvent such
as ethanol increases the catalytic activity of PM12Cin. A
conversion of 100% is observed at 8 h, with 90% selectivity
to sulfoxide (Table 1, entry 8). Water is also a good solvent
to perform this reaction, conversion of 100% and selectivity
of 95% was obtained in 3 h (Table 1, entry 11).
S
HPA
R
R´
R
R´
Oxidant
R = Aryl, Alkyl
Scheme 1.
used for sulfide oxidation. More recent methods include
gold(III)–hydrogen peroxide,27 silica-immobilized vanadyl
alkyl phosphonate–sodium bromate,28 and silica sulfuric
acid–hydrogen peroxide.29
In this Letter, we describe a procedure for the selective
oxidation of sulfides to sulfoxides (Scheme 1) using
Keggin-type structure catalysts, synthesized in our lab, by
partial proton substitution of H3PMo12O40 (PM12) on
different amines such as quinoline QuiH3PMo12O40
(PM12Qui), cinchonidine CidH3PMo12O40 (PM12Cid),
and cinchonine CinH3PMo12O40 (PM12Cin). They were
characterized by FT-IR, DRS, XRD, SBET, and in liquid
phase by 13C NMR.
Other oxidants such as urea–hydrogen peroxide 1:1
complex, sodium percarbonate and t-butyl-hydroperoxide
were used (Table 1, entries 9–14). Table 1, entry 9 shows
that the urea–hydrogen peroxide was the most active oxi-
dant. A conversion of 100% is observed at 20 °C and for
2 h with a 100% of the selectivity in the sulfoxide. On
increasing the reaction temperature, the conversion rate
increases and a higher selectivity to sulfone results. For
example, at 50 °C and for 3 h, a 100% selectivity to sulfone
is achieved (Table 1, entry 11).
The cinchonine and cinchonidine catalysts represent an
alternative for the enantioselective oxidation of sulfides to
sulfoxides. For example, entry 9 in Table 1, the sulfoxide
was obtained with a ratio of R:S 70:30, estimated by
polarimetry.
Once the reaction conditions for the selective oxidation of
sulfides to sulfoxides and sulfones had been optimized, the
reaction was extended to other starting substrates. Table 2
shows the results for the selective oxidation of different
sulfides to sulfoxides.30 All the reactions were run within a
very short time and the sulfoxides were obtained in excel-
lent yields, as practically the only oxidation product. For
We initially screened the oxidation of the methyl p-tolyl
sulfide using different HPAs, oxidants, solvents, and reac-
tion conditions (Table 1).
The reaction yields very low conversions in the absence
of a catalyst (10% for 20 h), at 20 °C using a stoichiometric
amount of 35% p/v hydrogen peroxide and acetonitrile as
solvent of the reaction (Table 1, entry 1) but when an
HPA is added, the times are reduced considerably and
the conversion increases to values close to 100%. When
commercial HPA such as H3PMo12O40 is used (Table 1,
entry 2), a conversion of 100% is observed at 3.5 h of reac-
tion, with 99% selectivity to sulfoxide. The hydrogen per-
oxide concentration effect on the selectivity of reaction
was studied. As can be observed, on increasing the hydro-
gen peroxide/sulfide molar ratio, the selectivity to sulfone
increases (Table 1, entry 3), and on increasing the temper-
ature, the conversion rate increases and a higher selectivity
Table 1
Selective oxidation of methyl p-tolyl sulfide to sulfoxide employing different HPAs as catalyst
Convn.a (%)
SO:SO2 (%)
a
Entry
Catalyst
Solvent
Oxidant (mmol)
Time (h)
Temp (°C)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
a
None
PM12
PM12
PM12
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CH2OH
CH3CH2OH
CH3CH2OH/H2O 4:1
H2Oc
CH3CH2OH
CH3CH2OH
CH3CH2OH
H2O2 (2)
H2O2 (2)
H2O2 (20)
H2O2 (2)
H2O2 (2)
H2O2 (2)
H2O2 (2)
H2O2 (2)
1:1 H2O2/urea (2)
1:1 H2O2/urea (2)
1:1 H2O2/urea (2)
1:1 H2O2/urea (20)
Na2CO3Á1.5H2O2 (2)
t-Butyl-hydroperoxide (2)
20
3.5
15
3
20
20
20
50
20
20
20
20
20
20
20
50
20
20
10
100:0
99:1
2:98
1:99
95:5
100
100
100
100
100
100
100
100
100
100
100b
100
100
PM12Qui
PM12Cid
PM12Cin
PM12Cin
PM12Cin
PM12Cin
PM12Cin
PM12Cin
PM12Cin
PM12Cin
3
15
15
8
2
2.5
3
3
7
21
93:7
95:5
90:10
100:0
100:0
95:5
0:100
100:0
100:2
Determined by GC analysis.
Ratio R:S 70:30. Estimated by polarimetry.
Methyl p-tolyl sulfide is insoluble in water.
b
c

A. G. Sathicq et al. / Tetrahedron Letters 49 (2008) 1441–1444
1443
Table 2
Table 3
Oxidation of sulfides to sulfoxides with 1:1 H2O2–urea catalyzed by
PM12Cina
Oxidation of methyl p-tolyl sulfide with 1:1 hydrogen peroxide–urea
catalyzed by reused PMo12Cina
Entry Substrate
Product
Yieldb
(%)
Entry
Catalyst
Yieldsb (%)
1
2
3
4
a
1st use
2nd use
3rd use
4th use
90
88
89
89
O
S
S
CH3
95c
1
CH3
The reactions were carried out with 1:2 substrate and 1:1 hydrogen
peroxide–urea at 20 °C.
O
b
Yields % of pure sulfoxide. Conversions were >99% by proton NMR;
S
CH3
S
only trace amounts of residual sulfide were observed, and oxidation was
generally selective with only trace amounts of sulfone seen in most cases.
Run time was 2 h.
2
CH3
100
82
H3C
H3C
O
S
S
S
O
CH3
C2H5
S
3
4
C2H5
PM12 Urea-H2O2
O
O
S
20 °C 3 h
H
N
EtO
H3C
80
CH3
N
H
O
S
85%
O
S
S
S
OH
O
5
6
96
1a
OH
H
N
EtO
H3C
O
S
N
H
O
CH3
O
S
O
88
1
PM12 Urea-H2O2
O
50 °C 3 h
H
N
EtO
H3C
O
S
7
8
9
97
93
N
H
O
S
S
73%
1b
O
S
Scheme 2.
O
S
S
derivatives can be oxidized selectively to new sulfoxides or
sulfones using these catalysts (Scheme 2). The sulfone
derivatives compounds are promising agents with potential
plant fungicides activity.
CH3
+
100
CH3
+
PhCHO
PhCHO
a
b
c
Reactions were carried out at 20 °C for 2 h.
Pure product yields.
Ratio R:S 60:40. Estimated by polarimetry.
As conclusions, we developed a procedure for the
selective oxidation of sulfides to sulfoxide using Keggin-
structure catalysts, synthesized in our lab, by partial proton
substitution on different amines such as quinoline
(PM12Qui), cinchonidine (PM12Cid), and cinchonine
(PM12Cin). First, methyl p-tolyl sulfide was used as
substrate, commercial PM12 as catalyst, and hydrogen
peroxide (35% (p/v)) and acetonitrile as solvent to optimize
homogeneous reaction conditions. The sulfoxides were
obtained at 20 °C, using a stoichiometric amount of hydro-
gen peroxide, in 3–4 h. Under this condition, sulfoxides
were obtained with a yield higher than 95%. Also, the sulf-
ones were obtained at 50 °C and with excess of hydrogen
example, entry 9 in Table 2, the benzaldehyde group was not
affected by the reaction conditions.
Due to the need to obtain catalysts for green processes,
the use of recycled catalysts is required for reducing the
catalytic cost. When the reaction was completed, the cata-
lyst (insoluble) was filtered, dried under vacuum (20 °C),
and reused. The catalyst was used and reused for four
cycles with similar activity (Table 3).
This protocol also represents a clean alternative to pre-
pare more sophisticated molecules.31 For example, Biginelli

1444
A. G. Sathicq et al. / Tetrahedron Letters 49 (2008) 1441–1444
23. Bonadies, F.; De Angelis, F.; Locati, L.; Scettri, A. Tetrahedron Lett.
1996, 37, 7129–7130.
24. Kaczorowska, K.; Kolarska, Z.; Mitka, K.; Kowalski, P. Tetrahedron
2005, 61, 8315–8327.
25. Sasaki, Y.; Ushimaru, K.; Iteka, K.; Nakayama, H.; Yamaguchi, S.;
Ichiara, J. Tetrahedron Lett. 2005, 45, 9513–9515.
26. Junes, S.; Gillitt, N.; Bunton, C. Colloid Surf. A: Phys. Eng. Asp.
2006, 281, 1–7.
peroxide with similar yields. The PM12Cin was an appro-
priate catalyst for carrying out this transformation in
heterogeneous medium. The p-tolyl sulfide oxidation at
20 °C, with 1:1 hydrogen peroxide–urea and ethanol
(96%) as solvent, gives 90% of the corresponding sulfoxide.
The catalyst was recovered and reused without loss of its
catalytic activity. The main advantages of this procedure
are the operational simplicity, the use of a noncorrosive,
reusable catalyst in mild, clean oxidation, and the very
good yields attained. The use of an insoluble catalyst
instead of soluble inorganic acids contributes to waste
reduction. Further investigations about the use of this
heterogeneous catalyst for enantioselective oxidations of
sulfides in sulfoxides are in progress.
27. Yuan, Y.; Bian, Y. Tetrahedron Lett. 2007, 48, 8518–8520.
28. Al-Hashimi, M.; Fisset, E.; Sullivan, A.; Wilson, J. Tetrahedron Lett.
2006, 47, 8017–8019.
29. Shaabani, A.; Rezayan, A. Catal. Commun. 2007, 8, 1112–1116.
30. The commercial catalyst H3PMo12O40 (PM12) was provided by
Aldrich. All the other catalysts were synthesized in our lab, by partial
proton substitution on different amines such as quinoline (PM12Qui),
cinchonidine (PM12Cid), and cinchonine (PM12Cin). Another ethan-
olic solution of the corresponding amine was added to an ethanolic
solution of H3PMo12O40. The mixture was stirred at 75 °C for 1.5 h
and concentrated. The precipitate was filtered, washed with more
ethanol and dried at 20 °C under vacuum. Catalysts were character-
ized by FT-IR, DRS, DRX, BET, and liquid 13C NMR.
General procedure of oxidation of sulfides to sulfoxide in homogeneous
Acknowledgments
The authors thank Consejo Nacional de Investigaciones
´
´
Cientıficas y Tecnicas (CONICET), Agencia Nacional de
conditions.
A stirred solution of sulfide (1 mmol) and catalyst
´
´
´
promocion cientıfica y tecnologica and Universidad de La
Plata for the financial support. G.P.R., P.G.V. and
H.J.T. are members of CONICET.
(0.01 mmol), in acetonitrile or ethanol (5 ml), was added to H2O2
35% p/v (2 mmol) at 20 °C. The mixture was stirred at 20 °C for a
time period (see Table 1). The solvent was evaporated and then H2O
(5 ml) was added. The substrate was extracted with toluene (2 Â 5 ml)
and dried with anhydrous Na2SO4; filtration and evaporation
afforded the corresponding pure crude sulfoxides. The solid sulfoxides
were purified by recrystallization to afford the pure products. The
products were confirmed by 1H NMR and 13C NMR analyses.
General procedure of oxidation of sulfides to sulfoxide in heterogeneous
References and notes
1. Kozhevnikov, I. Appl. Catal. A: Ger. 2004, 256, 3–18.
2. Misono, M. Catal. Rev. Sci. Eng. 1997, 29, 269–321.
3. Davis, M.; Dillon, C.; Holles, J.; Labinger, J. Angew. Chem., Int. Ed.
2002, 41, 858–860.
4. Okuhara, T.; Mizuno, N.; Misono, M. Appl. Catal. A: Ger. 2001, 222,
63–77.
5. Izumi, Y.; Urabe, K.; Onaka, M. Catal. Today 1997, 35, 183–188.
6. Romanelli, G.; Vazquez, P.; Pizzio, L.; Caceres, C.; Blanco, M.;
Autino, J. Synth. Commun. 2003, 33, 1359–1365.
7. Romanelli, G.; Vazquez, P.; Quaranta, N.; Pizzio, L.; Autino, J.;
Caceres, C.; Blanco, M. Appl. Catal. A: Ger. 2004, 261, 163–170.
8. Romanelli, G.; Autino, J.; Blanco, M.; Pizzio, L. Appl. Catal. A: Ger.
2005, 295, 209–215.
9. Va´zquez, P.; Pizzio, L.; Romanelli, G.; Autino, J.; Ca´ceres, C.;
Blanco, M. Appl. Catal. A: Ger. 2002, 235, 233–240.
10. Pizzio, L.; Romanelli, G.; Vazquez, P.; Autino, J.; Blanco, M.;
Caceres, C. Appl. Catal. A: Ger. 2006, 308, 153–160.
11. Villabrille, P.; Romanelli, G.; Vazquez, P.; Caceres, C. Appl. Catal:
Ger. 2004, 270, 101–111.
12. Romanelli, G.; Bennardi, D.; Palermo, V.; Vazquez, P.; Tundo, P.
conditions.
A stirred solution of sulfide (1 mmol) and catalyst
(0.01 mmol), in acetonitrile or ethanol (5 ml), was added to 1:1
hydrogen peroxide–urea (2 mmol), at 20 °C. The mixture was stirred
at 20 °C for a time period (see Table 1). The catalyst was filtered and
reused. The solvent was evaporated and then H2O (5 ml) was added.
The substrate was extracted with toluene (2 Â 5 ml) and dried with
anhydrous Na2SO4; filtration and evaporation afforded the corres-
ponding pure crude sulfoxides. The solid sulfoxides were purified by
recrystallization to afford the pure products. The products were
confirmed by 1H NMR and 13C NMR analyses.
Sample analysis. Samples were withdrawn from the organic phase at
15 minute intervals. Each volume sample was approximately 20 ll
and it was diluted with 1–2 ml of acetonitrile or ethanol, the
concentrations of which were calculated with internal standard
method. Conversions were obtained with CG analysis performed
with a Varian GC 3400 instrument. The capillary column was a 30 m
Chromopack CP Sil 8 CB, whose diameter was 0.32 mm in diameter.
The identification of products was performed with GC–MS (detector
HP 5971) for comparison with GC–MS authentic samples.
´
´
´
´
´
´
´
´
´
Lett. Org. Chem. 2007, 4, 544–549.
31. Compound 1a: mp 183–184 °C. 1H NMR (DMSO-d6, 200 MHz):
d = 1.10 (t, J = 7 Hz, 3H), 2.27 (s, 3H), 2.72 (s, 3H), 3.99 (q, J = 7 Hz,
2H), 5.21 (d, J = 3.2 Hz, 1H), 7.41–7.67 (m, 4H), 7.82 (s, 1H), 9.28 (s,
1H). 13C NMR (DMSO-d6, 50 MHz): d = 14.55, 18.32, 43.64, 54.21,
59.77, 99.24, 124.37, 127.63, 140.22, 149.68, 150.75, 152.46, 165.69.
Anal. Calcd for C15H18N2O4S: C, 55.88; H, 5.63; N, 8.69. Found: C,
55.83; H, 5.65; N, 8.72.
13. Results not published yet.
´
14. Romanelli, G.; Vazquez, P.; Tundo, P. Synlett 2005, 75–78.
15. Trost, B. Chem. Rev. 1978, 78, 363–382.
16. Carreno, M. Chem. Rev. 1995, 95, 1717–1760.
17. Karami, B.; Ghoreishi-Nezhad, M.; Clark, J. Org. Lett. 2005, 7, 625–
628.
18. Varma, R.; Sain, R.; Meshram, H. Tetrahedron Lett. 1997, 38, 6525–
6528 and references cited therein.
19. Tajbakhsh, M.; Hosseinzadeh, R.; Shakoori, A. Tetrahedron Lett.
2004, 45, 1889–1893 and references cited therein.
20. Barton, D.; Li, W. Tetrahedron Lett. 1998, 39, 7075–7078.
21. Iwahana, T.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1998, 39,
9059–9062.
Compound 1b: mp 200–202 °C. 1H NMR (DMSO-d6, 200 MHz):
d = 1.10 (t, J = 7 Hz, 3H), 2.27 (s, 3H), 3.19 (s, 3H), 3.99 (q, 2H), 5.25
(d, J = 3.2 Hz, 2H), 7.48–7.88 (m, 4H), 7.92 (s, 1H), 9.32 (s, 1H). 13
C
NMR (DMSO-d6, 50 MHz): d = 14.75, 18.55, 44.21, 54.40, 60.05,
99.09, 127.91, 128.03, 140.42, 149.90, 150.95, 152.53, 165.82. Anal.
Calcd for C15H18N2O5S: C, 53.24; H, 5.36; N, 8.28. Found: C, 53.26;
H, 5.37; N, 8.25.
22. Martin, S.; Rossi, L. Tetrahedron Lett. 2001, 41, 7147–7151.