Oxidation of sulfides to sulfoxides with H2O2/HNO3 reagent system

Article abstract of DOI:10.1080/17415991003664763

Selective oxidation of sulfides to sulfoxides is achieved by H₂O₂ using HNO₃ as the promotor. Aromatic and aliphatic sulfides are oxidized to sulfoxides in excellent yields and short reaction times. Different functional groups including C-C double bond, ester, ketone, acetal, alcohol, and oxime groups are tolerated under this reaction condition.

Full text of DOI:10.1080/17415991003664763

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Oxidation of sulfides to sulfoxides with
H O /HNO reagent system
2
2
3
a b
a b
Mohammad Mehdi Khodaei
, Kiumars Bahrami
& Mehdi
a
Sheikh Arabi
a
Department of Chemistry , Razi University , Kermanshah, 67149,
Iran
b
Nanoscience and Nanotechnology Research Center (NNRC) , Razi
University , Kermanshah, 67149, Iran
Published online: 07 Apr 2010.
To cite this article: Mohammad Mehdi Khodaei , Kiumars Bahrami & Mehdi Sheikh Arabi (2010)
Oxidation of sulfides to sulfoxides with H O /HNO reagent system, Journal of Sulfur Chemistry,
2
2
3
31:2, 83-88, DOI: 10.1080/17415991003664763
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Journal of Sulfur Chemistry
Vol. 31, No. 2, April 2010, 83–88
Oxidation of sulfides to sulfoxides with H O /HNO
3
2
2
reagent system
Mohammad Mehdi Khodaeia,b*, Kiumars Bahramia,b* and Mehdi Sheikh Arabia
a
b
Department of Chemistry, Razi University, Kermanshah 67149, Iran; Nanoscience and Nanotechnology
Research Center (NNRC), Razi University, Kermanshah 67149, Iran
(Received 7 November 2009; final version received 18 January 2010)
Selective oxidation of sulfides to sulfoxides is achieved by H2O2 using HNO3 as the promotor. Aromatic
and aliphatic sulfides are oxidized to sulfoxides in excellent yields and short reaction times. Different
functional groups including C–C double bond, ester, ketone, acetal, alcohol, and oxime groups are tolerated
under this reaction condition.
Keywords: nitric acid; hydrogen peroxide; sulfoxide synthesis; sulfides; chemoselectivity
1
.
Introduction
Much effort has been devoted to the development of highly efficient and atom-economical organic
transformations in order to realize environmentally benign processes. Sulfoxides are useful syn-
thetic intermediates in the synthesis of drugs and natural products (1, 2). They have been utilized
extensively in carbon–carbon bond-forming reactions, molecular rearrangements, and functional-
group transformations (3, 4). The increasing interest in, and applications of, sulfoxides have
stimulated investigations on new methodologies of sulfoxide synthesis.
The direct oxidation of sulfides is one of the most important and widely studied reactions for
the preparation of sulfoxides. The popularity of this method is due to the availability of a wide
variety of sulfides that can be utilized in the oxidation of sulfides to the corresponding sulfoxides.
Thus, the oxidation of sulfides to sulfoxides has been the subject of extensive studies, and a variety
of procedures for this purpose are available (5–7).
Although different approaches have been reported, there are various limitations, such as long
reaction times, hazardous organic solvents and reagents, transition metal catalysts, expensive
oxidants, undesired side reactions at other functionalities accompanied by overoxidation to the
sulfone, and low yields.
Aqueous hydrogen peroxide (30%) is an ideal oxidant in view of its high effective-oxygen
content, its eco-friendly by-product (water), its relative safety in storage and operation, and its
comparatively low cost of production and transportation (8, 9).
*
Corresponding authors. Email: Kbahrami2@hotmail.com; mmkhoda@razi.ac.ir
ISSN 1741-5993 print/ISSN 1741-6000 online
2010 Taylor & Francis
©
DOI: 10.1080/17415991003664763
http://www.informaworld.com

8
4 M.M. Khodaei et al.
O
S
H O –HNO
3
2
2
R
S
R'
R
R'
o
EtOH, 25 C
R, R′ = Alkyl, aryl
Scheme 1. Formation of sulfoxides from sulfides.
Recently, we reported several new synthetic methods for environmentally benign reactions
using aqueous 30% hydrogen peroxide (10). Now we wish to report a facile and selective method
in which H2O2 has been used as the oxidizing agent in the presence of HNO3 for the oxidation
of sulfides to their sulfoxides in excellent yields (Scheme 1).
Table 1. Selective oxidation of sulfides using the H2O2 (2 equivalents)/HNO3 (1 equivalent) system in ethanol.a
O
R
S
R'
R
S
R'
Yield %b
Mp ( C)
◦
Yield %b Mp ( C)
◦
Entry
1
Sulfoxide
(t (min))
(ref.)
Entry
8
Sulfoxide
(t (min)) (ref.)
O
S
N
O
S
96 (7)
120–121 (11a)
95 (25) 171 (11f )
98 (14) Oil (11g)
N
H
NO
2
O
O
S
O
2c
S
97 (20)
162 (10a)
9
O
O
S
O
S
3
4
100 (18)
92 (40)
143 (11b)
68 (11c)
10
11
98 (4)
28 (10c)
Br
O
O
S
S
100 (3) Oil (11d)
93 (23) 201 (11h)
O
O
S
5
98 (12) 121–122 (11d) 12d
S
Me
O
Br
O
S
Br
6
7
97 (20)
97 (10)
158 (11e)
Oil (11f )
13c
14
O
S
96 (14) 137 (10a)
97 (10) 30 (10c)
Me
O
S
O
S
Notes: aThe products were characterized by comparison of their spectroscopic and physical data with authentic samples synthesized by
b
c
d
reported procedures. Isolated yields. Accompanied by sulfone <5%. 1,4-Dioxane was used as the solvent.

Journal of Sulfur Chemistry 85
2
.
Result and discussion
The choice of the organic solvent is of particular importance. Only ethanol was found suitable,
giving rise to a relatively fast reaction rate at room temperature, while solvents such as
dichloromethane, chloroform, toluene, and ethyl acetate had to be discarded.
The optimum ratio of sulfide to H2O2 to HNO3 (1:2:1 equivalents) is found to be ideal for
complete conversion of sulfides to sulfoxides, while with lesser amounts (for example, 1:2:0.75
and 1:1.5:1) the reaction remains incomplete. The use of excess oxidant (for example, 1:3:1
equivalents) increases the contamination of sulfone (<15%). Furthermore, HNO3 is an effective
agent only in the presence of H2O2. We studied the oxidation of 1 mmol of diphenyl sulfide as a
model compound with 1 mmol of 65% HNO3 as the oxidant. It was found that the reaction did
not proceed at all after 2 h.
The generality of the method was examined using alkyl aryl, dialkyl, diaryl, cyclic, and
heterocyclic sulfides (Table 1). It was discovered that a wide variety of sulfides can be selectively
oxidized by this inexpensive system under mild conditions. The reagent system was chemos-
elective, tolerating various functional groups, such as carbonyl, nitro, C−C double bonds, and
halide. Diphenyl sulfide may exert a little steric hindrance for oxidation as exhibited by the
longer time of 40 min with 92% yield (Entry 4). The protocol worked efficiently in oxidizing
2
-(benzylthio)benzimidazole to afford the corresponding sulfoxide (Entry 8). Interestingly, the
presence of the ester group did not interfere with the oxidation process of the sulfide and desired
sulfoxide was obtained in excellent yield (Entry 9).
In order to show the chemoselectivity of this method, we have also carried out several com-
petitive reactions. The experimental results show that the reaction tolerates sensitive functional
groups such as ester, acetal, alcohol, and oxime, and only the sulfur atom is selectively oxidized
(Scheme 2). These observations clearly show that the method is applicable to the selective oxida-
tion of sulfides in the presence of the earlier-mentioned functional groups and can be considered
as a useful practical achievement for this transformation.
To access the feasibility of applying this method in a preparative scale, we carried out the
oxidation of benzyl phenyl sulfide on a 30 mmol scale. As expected, the reaction proceeded
smoothly, similar to the case on a smaller scale (Entry 1), and the desired product was obtained
in 97% isolated yield.
O
C H
S
S
C H
+
+
C H CO Me
C H
S
C H
+
C H COOH
6 5
6
5
5
6
5
6
5
2
6
5
6
5
9
0%
0%
O
S
O
O
C H
Me
Ph
C H
Me
+
Ph CHO
0%
6
6
5
9
5%
O
S
C H
S
CH C H
+
C H CH OH
C H
CH C H
+
C H CHO
6
5
2
6
5
6
5
2
6
5
2
6
5
6
5
95%
0%
O
Bu S Bu
+
C H
C
H
NOH
Bu S Bu
+
C H N CHO
6 5
6
5
H
96%
0%
Scheme 2. Reagents and conditions: molar ratio of substrates to H2O2 to HNO3 (1:1:2:1), EtOH,
◦
2
5 C.

8
6 M.M. Khodaei et al.
HO OH
R'
+
+
HNO3
HO OH2
+
NO3
H
O
.
S.
HO OH2
R
S R'
R
-H2O
-
H
O
R
S R'
Scheme 3. Proposed mechanism for the oxidation of sulfides.
The possible mechanism for oxidation of sulfides to the corresponding sulfoxides using H2O2
in the presence of HNO3 is outlined in Scheme 3.
3
. Conclusion
In conclusion, nitric acid promotes the chemoselective and efficient oxidation of sulfides to sulfox-
ides with the environmentally friendly 30% H2O2, under mild reaction conditions. This method
offers the advantage of shorter reaction times, excellent yields, large-scale synthesis, high chemos-
electivity, and easy work-up. Therefore, our method can be considered the most outstanding
methodology of sulfoxidation.
4
4
.
Experimental
.1. General procedure
The sulfide (3 mmol) dissolved in EtOH (15 mL) was treated with 30% H2O2 (6 mmol, 0.6 mL)
◦
and 65% HNO3 (3 mmol, 0.2 mL). After stirring at 25 C for the time required, the reaction
mixture was quenched by adding water (30 mL), extracted with ethyl acetate, and the extract
dried with anhydrous MgSO4. The filtrate was evaporated and the corresponding sulfoxide was
obtained as the only product. Spectral data for selected compounds follow.
4
.1.1. Entry 1, Table 1: benzyl phenyl sulfoxide
IR (KBr): 1034 cm 1.
−
1
H NMR (200 MHz, CDCl3): δ = 3.99 (d, J = 12.53 Hz, 1H), 4.11 (d, J = 12.53 Hz, 1H),
7
.96–7.00 (m, 2H), 7.22–7.30 (m, 3H), 7.36–7.46 (m, 5H).
C NMR (50 MHz, CDCl3): δ 63.5, 124.4, 128.2, 128.4, 128.8, 129.1, 130.4, 131.2, 142.7.
1
3
4
.1.2. Entry 7, Table 1: diallyl sulfoxide
IR (neat): 1035, 1621 cm 1.
−
1
H NMR (200 MHz, CDCl3): δ = 3.04 (m, 2H), 3.07 (m, 2H), 5.00–5.09 (m, 4H), 5.66–5.80
3C NMR (50 MHz, CDCl3): δ 33.6, 117.5, 134.6.
(m, 2H).
1

Journal of Sulfur Chemistry 87
4
.1.3. Entry 8, Table 1: (benzimidazol-2-yl) benzyl sulfoxide
IR (neat): 1023 cm 1.
−
1
H NMR (200 MHz, CDCl3): δ = 4.32 (d, J = 13.2 Hz, 1H), 4.56 (d, J = 13.2 Hz, 1H,), 7.04–
7
.40 (m, 8H), 7.61–7.64 (m, 2H).
C NMR (50 MHz, CDCl3): δ 60.3, 115.3, 122.8, 123.2, 127.3, 127.6, 127.8, 129.4, 150.9.
1
3
4
.1.4. Entry 9, Table 1: Methyl 2-(phenylsulfinyl)acetate
IR (neat): 1038 cm 1.
−
1
H NMR (200 MHz, CDCl3): δ = 3.65 (d, J = 13.6 Hz, 1H), 3.68 (s, 3H), 3.83 (d, J = 13.6 Hz,
1
H), 7.50–7.53 (m, 3H), 7.64–7.67 (m, 2H).
C NMR (50 MHz, CDCl3): δ 51.8, 60.5, 123.0, 128.4, 130.8, 141.9, 164.2.
1
3
4
.1.5. Entry 11, Table 1: allyl phenyl sulfoxide
IR (neat): 1043, 1660 cm 1.
−
1
H NMR (200 MHz, CDCl3): δ = 3.37–3.57 (m, 2H), 5.08–5.28 (m, 2H), 5.47–5.68 (m, 1H),
7
.42–7.54 (m, 5H).
1
3
C NMR (50 MHz, CDCl3): δ 60.7, 123.9, 124.3, 125.2, 129.0, 131.1, 142.8.
4
.1.6. Entry 13, Table 1: Benzyl 4-bromobenzyl sulfoxide
IR (KBr, cm 1) 1029.
−
1
H NMR (500 MHz, CDCl3) δ: 3.78 (d, J = 13.1 Hz, 1H), 3.89 (d, J = 13.1 Hz, 1H), 3.95 (s,
2
H), 7.2 (d, J = 8.3 Hz, 2H), 7.32–7.33 (m, 2H), 7.40–7.44 (m, 3H), 7.54 (d, J = 8.3 Hz, 2H).
C NMR (50 MHz, CDCl3): δ 56.2, 57.5, 122.6, 128.4, 129.1, 129.2, 129.8, 130.1, 131.8, 132.1.
1
3
Acknowledgements
We are thankful to the Razi University Research Council for the partial support of this work.
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