Oxidation of sulfides with N-bromosuccinimide in the presence of hydrated silica gel

Article abstract of DOI:10.1080/00397910600618988

An efficient and highly selective procedure for oxidation of sulfides to sulfoxides with N-bromosuccinimide (NBS) in the presence of hydrated silica gel has been developed. Hydrated silica gel supplies the water necessary for decomposition of the intermed

Full text of DOI:10.1080/00397910600618988

w
Synthetic Communications , 36: 1769–1777, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600618988
Oxidation of Sulfides
with N-Bromosuccinimide in the Presence
of Hydrated Silica Gel
Mohammed Hashmat Ali, Melanie Hartman, Kimberly Lamp,
Chad Schmitz, and Tim Wencewicz
Department of Chemistry, Southeast Missouri State University,
Cape Girardeau, Missouri, USA
Abstract: An efficient and highly selective procedure for oxidation of sulfides to sulf-
oxides with N-bromosuccinimide (NBS) in the presence of hydrated silica gel has been
developed. Hydrated silica gel supplies the water necessary for decomposition of the
intermediate bromosulfonium salt to the product, allowing the reaction to employ a
nonaqueous media. Also, this procedure has increased the scope of the reaction by
oxidizing a wider variety of sulfides, which was not possible until now.
Keywords: N-Bromosuccinimide, NBS, oxidation, silica gel, sulfides, sulfoxides
Oxidation of sulfides is a widely utilized method for sulfoxide synthesis. This
transformation can be performed with a wide variety of reagents. Among these
[
1–3]
are N-halogenated regents, such as, N-bromosuccinimide (NBS),
[5]
[
2,4]
[5]
N-chlorosuccinimide,
chloramine and bromamine-T,
N-bromocaprolacturn,
[
N-chloro-6,6-nylon,
[11]
N-bromopyridine, and 1-chlorobenzo-
6–10]
[
12]
triazole. These reagents are capable of oxidizing sulfides to the correspond-
ing sulfoxides in alcohol or in aqueous–organic mixed solvent media. A
suggested general mechanism for oxidation of sulfides with N-halogenated
reagents has been summarized in Scheme 1.
The reaction between a sulfide 1 and an N-halogenated reagent, the source
of the electrophilic halogen species, initially produces an unstable
Received in the USA, December 7, 2005
Address correspondence to Mohammed Hashmat Ali, Department of Chemistry,
Southeast Missouri State University, Cape Girardeau, Missouri 63701, USA.
Tel.: 573-651-2983; Fax: (573) 986-6433; E-mail: mhali@semo.edu
1
769

1
770
M. H. Ali et al.
Scheme 1.
intermediate halosulfonium salt (I). Alcohol, if used as the reaction media,
transforms intermediate (I) to intermediate alkoxysulfonium salt (II).
Finally, intermediate (II) undergoes decomposition to produce sulfoxide 2.
If the reaction is carried out in a wet aprotic solvent, the unstable halosul-
fonium salt (II) decomposes to produce sulfoxide 2 directly.
Previously reported sulfide oxidation reactions utilizing N-halogenated
reagents suffer from various drawbacks. N-Bromosuccinimide in aqueous–
organic biphase reaction media oxidizes aryl sulfides to the corresponding
sulfoxides but fails to oxidize alkyl-aryl and dialkyl sulfides to the expected
[1]
sulfoxides because of C-S bond cleavage. Sulfide oxidation with 1-chloro-
benzotriazole requires low temperature (2788C) and works, for only diaryl
[
12]
sulfides.
This reagent does not produce good results in the oxidation of
dibenzyl and certain dialkyl sulfide, also because of C-S bond cleavage.
In our previously reported procedure for oxidation of sulfides to sulfox-
ides with molecular bromine, we utilized hydrated silica gel, which among
other advantages, provided the water necessary to decompose the bromosulfo-
[13]
nium salt to the final sulfoxide product. Utilization of hydrated silica gel as
the source for water in this reaction allowed us to employ a nonaqueous dicho-
loromethane media in this reaction. In the past, aqueous–organic biphasic
media employed in such reactions was the source of water necessary to
complete the reaction. Oxidation of sulfides with N-bromosuccinimide,
similar to oxidation of sulfides with bromine, also proceeds through
unstable bromosulfonium salt intermediates, which decompose in the
presence of protic solvent to sulfoxides. Therefore, we became interested in
employing hydrated silica gel in the later reaction to explore the possibility
of replacing the aqueous–organic reaction media, traditionally employed in
this reaction, with a nonaqueous dichloromethane media.
Herein we report the results of our investigation. Oxidation of sulfides
with N-bromosuccinimide in the presence of hydrated silica gel using

Oxidation of Sulfides with N-Bromosuccinimide
1771
dichloromethane solvent produced excellent results and also proved to be
superior to the previously reported procedures. Hydrated silica gel offers a
number of benefits to this reaction procedure. Hydrated silica gel eliminates
the need for aqueous–organic biphasic reaction media that provide the
[
1–8]
necessary water.
Hydrated silica gel produces greater selectivity in the
oxidation of sulfides by suppressing potential side reactions. Oxidation of
diaryl, alkyl-aryl, and dialkyl sulfides under these reaction conditions
produces the corresponding sulfoxides in excellent yields (Table 1).
Oxidation of aryl-alkyl or dialkyl sulfides, except for the highly sterically
hindered sulfide 1c, proceeds smoothly without any observable C-S bond
cleavage. Others have reported low yield for the oxidation of 1c to 2c using
Table 1. Oxidation of sulfides 1 to sulfoxides 2
Rxn. time
(min)
Yield
(%)
Entry
Sulfide (1)
a
20
99
b
22
92
c
180
25
85
99
d
e
f
30
30
95
92
g
35
98
h
i
10
10
99
97
(Continued)

1
772
M. H. Ali et al.
Table 1. Continued
Rxn. time
(min)
Yield
(%)
Entry
Sulfide (1)
j
15
60
99
93
k
l
45
35
95
90
m
n
o
150
210
86
92
p
q
240
60
74
96
r
50
98
s
t
60
50
97
93

Oxidation of Sulfides with N-Bromosuccinimide
1773
[14]
benzyltrimethylammonium tribromide as the oxidizing reagent.
We have
not observed any oxidation of the alcohol functional group present in sulfide
m; bromination at the a-position of the carbonyl group present in sulfides
1
in, q–t; or bromination at the aromatic ring present in sulfides 1f–q, s–t. In
this reaction, hydrated silica gel acts as a heat sink, allowing us to carry out
this exothermic reaction safely at room temperature without further control-
ling the reaction temperature. We did not observe any rise in the reaction temp-
erature during the course of this reaction. Until now, NBS oxidation of dialkyl
sulfides were successful only in anhydrous alcohol media at low reaction
[
2]
temperatures. As expected, oxidation of thioanisoles 1k–1 carrying a deac-
tivating group on the benzene ring took a longer time to finish the reaction as
compared to the thioanisole 1i, which carries an activating group. Sterically
hindered sulfides lc, lg, and 1n–p reacted sluggishly, as expected.
Our newly developed procedure is a simple, convenient, fast, and efficient
procedure for oxidation of dialkyl, aryl-alkyl, and diaryl sulfides to the corres-
ponding sulfoxides in high yields. By allowing the oxidation of dialkyl and
aryl-alkyl sulfides without any complication from side reactions, this
procedure increased the scope of this reaction.
EXPERIMENTAL
General Procedure
Distilled water (2.00 mL) was added drop by drop to 5.0 g of silica gel (40–64-
mm mesh) placed in a 100-mL round-bottomed flask. The mixture was stirred
using a magnetic stirrer until a free-flowing solid was obtained (less than
5
min). CH Cl (15 mL) was added to the flask, followed by the addition of
2 2
a solution of 2.0 mmol of the sulfide under investigation. While stirring, a
solution of 2.2 mmol of N-bromosuccinimide in 10 mL of CH Cl (a cloudy
2
2
yellow solution) was added drop by drop to the reaction flask. A transient
yellow color was observed when N-bromosuccinimide hit the reaction
mixture. Once all the N-bromosuccinimide was added, the color of the
reaction mixture remained light yellow-orange. Progress of the reaction was
monitored by TLC. Once the reaction was complete, the reaction mixture
was filtered using a fritted glass funnel, and the solid residue was washed
with 70–75 mL of CH Cl . The combined organic phase was then transferred
2
2
into a separatory funnel and extracted with three 20-mL portions of distilled
H O and finally with 20 mL of saturated aqueous sodium chloride solution.
2
The organic layer was dried over anhydrous magnesium sulfate. After
removing the drying agent by filtration, the solvent was removed using a
rotary evaporator. The isolated products were determined to be pure by
NMR. The products were characterized by NMR (proton and carbon) and
IR. We obtained identical results when solid NBS, instead of a solution,
was added to the reaction mixture in small portions. All sulfoxide products

1
774
M. H. Ali et al.
were characterized by comparison of the NMR data with those of the
previously reported in the literature.
[15–18]
Data
1
Dibutylsulfoxide (2a). H NMR (CDCl ) 0.97 (t, J ¼ 7.1 Hz, 6H), 1.40–1.60
3
1
3
(
m, 4H), 1.74–1.78 (m, 4H). 2.68 (t, J ¼ 7.5 Hz, 4H). C NMR (CDCl )
3
1
2
3.70, 22.10, 24.60, 52.10. IR (film) 732, 908, 1024, 1381, 1407, 1460,
876, 2933, 2962 cm
2
1
.
1
Sec-butyl methyl sulfoxide (2b). H NMR (CDCl ) 0.92 (t, J ¼ 4 Hz,
3
3
H), 0.97 (t, J ¼ 7.2 Hz, 3H), 1.08 (d, J ¼ 7.0 Hz, 3H), 1.20
(
d, J ¼ 6.8 Hz, 3H), 1.28–1.49 (m, 2H), 1.80–1.86 (m, 2H), 2.42–2.46
3 3
1
3
m, 1H), 2.47 (s, 2CH , 6H), 2.64–2.66 (m, 1H). C NMR (CDCl ) 10.68,
(
1
1
0.75, 11.15, 11.32, 22.60, 23.10, 33.85, 34.30, 57.71, 58.20. IR (film) 951,
2
1
030, 1386, 1425, 1460, 2881, 2936, 2975 cm
.
1 13
Di-tert-butyl sulfoxide (2c). H NMR (CDCl ) 1.32 (s). C NMR (CDCl3)
3
2
2
5.40, 57.20. IR (film) 1021, 1178, 1230, 1375, 1466, 1470, 2874, 2932,
1
2
971 cm
.
1
Tetrahydrothiophene oxide 2d. H NMR (CDCl ) 2.00–2.25 (m, 2H), 2.35–
3
1
3
2
1
.50 (m, 2H), 2.80–2.86 (m, 4H). C NMR (CDCl ) 24.56, 53.40 IR (film)
3
2
1
021, 1215, 1325, 1456, 2885, 2960 cm
.
1
-Oxo-1,4-thioxane (2e). H NMR (CDCl ) 2.60–2.66 (m, 2H), 2.84–2.87
4
(
3
1
3
m, 2H), 3.80–3.85 (m, 2H), 4.30–4.38 (m, 2H). C NMR (CDCl ) 46.30,
3
5
2
9.20. IR (film) 1020, 1031, 1066, 1120, 1225, 1395, 1410, 1475, 2872,
935, 2978 cm
21
.
1
Benzyl methyl sulforide (2f). H NMR (CDCl ) 2.45 (s, 3H), 3.86
3
1
3
(
d, J ¼ 8 Hz, 1H), 4.10 (d, J ¼ 8 Hz, 1H), 7.25–7.45 (m, 5H). C NMR
(
CDCl ) 37.45, 60.32, 128.46, 128.94, 129.62, 130.10 IR (film) 1021, 1260,
3
2
1
1
365, 1452, 1505, 2920, 3010, 3060 cm
.
1
Benzyl phenyl sulfoxide (2g). H NMR (CDCl ) 4.02 (d, J ¼ 12.4 Hz, 1H),
3
4
7
1
2
.10 (d, J ¼ 12.4 Hz, 1H), 6.92–7.00 (m, 2H), 7.20–7.35 (m, 3H), 7.38–
1
.48 (m, 5H). C NMR (CDCl ) 63.20, 124.45, 128.20, 128.38, 128.83,
3
3
28.92, 130.35, 131.23, 142.16. IR (film) 695, 752, 1038, 1085, 1446, 1490,
2
1
915, 2972, 3060 cm
.
1
Methyl phenyl sulfoxide (2h). H NMR (CDCl ) 2.72 (s, 3H), 7.51–7.56
3
1
3
(
m, 3H), 7.64–7.67 (m, 2H). C NMR (CDCl ) 43.90, 123.44, 129.33,
3
1
2
31.0, 145.60. IR (film) 732, 955, 1092, 1296, 1415, 1446, 1471, 2923,
980, 3065 cm
21
.
1
Methyl p-methylphenyl sulfoxide (2i). H NMR (CDCl ) 2.40 (s, 3H), 2.68
3
1
3
(
s, 3H), 7.31 (d, J ¼ 8.4 Hz, 2H), 7.54 (d, J ¼ 8.4 Hz, 2H); C NMR (CDCl3)

Oxidation of Sulfides with N-Bromosuccinimide
1775
2
2
1.50, 44.00, 123.62, 130.12, 141.50, 142.62 IR (film) 808, 1042, 1080, 1495,
2
1
872, 2926, 2982, 3052 cm
.
1
Ethyl phenyl sulfoxide (2j). H NMR (CDCl ) 1.20 (t, J ¼ 7.4 Hz, 3H),
3
1
3
2
5
2
.72–2.92 (q, J ¼ 7.4 Hz, 2H), 7.50–7.62 (m, 5H). C NMR (CDCl ) 5.90,
3
0.20, 124.10, 129.00, 130.90, 143.16. IR (film) 732, 1048, 13.80, 1481,
877, 2937, 2983, 3065 cm
2
1
.
1
Methyl p-nitrophenyl sulfoxide (2k). H NMR (CDCl ) 2.81 (s, 3H), 7.86
3
1
3
(
d, J ¼ 8.8 Hz, 2H), 8.38 (d, J ¼ 8.8 Hz, 2H). C NMR (CDCl ) 43.90,
3
1
2
24.40, 124.60, 149.40, 153.26. IR (film) 750, 980, 1038, 1042, 1346, 2865,
.
2
1
926, 3030 cm
1
-Bromophenyl methyl sulfoxide (2l). H NMR (CDCl ) 2.70 (s, 3H). 7.52
4
(
3
1
3
d, J ¼ 9 Hz, 2H), 7.65 (d, J ¼ 9 Hz, 2H). C NMR (CDCl ) 43.84, 125.12,
3
1
3
25.34, 132.48, 144.90. IR (film) 1010, 1044, 1388, 1476, 2868, 2930,
032 cm
2
1
.
1
-Hydroxymethylphenyl methyl sulfoxide (2m). H NMR (CDCl ) 2.65
4
3
(
s, 3H), 3.16 (bs, OH), 4.66 (s, 2H), 7.49 (d, J ¼ 8.6 Hz, 2H), 7.54
1
3
(
d, J ¼ 8.6 Hz, 2H). C NMR (CDCl ) 43.26, 63.60, 123.54, 127.32,
3
1
3
40.96, 145.20. IR (film) 826, 967, 1098, 1210, 1312, 1430, 2880 2926,
020, 3058, 3364 cm
2
1
.
1
Thiooxochroman-4-one-S-oxide (2n). H NMR (CDCl ) 2.85–2.89 (m, 1H),
3
3
1
2
.38–3.43 (m, 3H), 7.66 (dd, J ¼ 7.5, 7.4 Hz, 1H), 7.70 (dd, J ¼ 7.5, 7.4 Hz,
1
3
H), 7.92 (d, J ¼ 7.5 Hz, 1H), 8.12 (d, J ¼ 7.4 Hz, 1H). C NMR (CDCl )
3
9.69, 45.97, 127.78, 128.20, 128.56, 131.45, 133.98, 145.00, 191.45. IR
.
2
1
(film) 785, 1056, 1182, 1296, 1336, 1443, 2945, 2975, 3016, 3068 cm
1
Thioxanthanone S-oxide (2o). H NMR (CDCl ) 7.35–7.50 (m, 2H), 7.55–
3
1
3
.64 (m, 2H), 8.55–8.70 (m, 2H). C NMR (CDCl ) 125.86, 126.26, 129.15,
7
1
3
3
29.80, 132.20, 137.25, 180.60. IR (film) 1069, 1158, 1328, 1445, 1581, 1646,
2
1
058 cm
.
1
Diphenyl sulfoxide (2p). H NMR (CDCl ) 7.40–7.45 (m, 6H), 7.58–7.65
3
1
m, 4H). C NMR (CDCl ) 124.70, 129.33, 130.90, 145.46. IR (film) 738,
3
(
3
2
1
1
042, 1145, 1443, 1474, 3062 cm
.
Ethyl-a-sulfinylphenylpropionate (2q). (about 2:1 diastereomeric mixture).
1
H NMR (CDCl ) 1.18 (t, J ¼ 7.4 Hz, 3H ). 1.20 (t, J ¼ 7.4 Hz, 3H ). 1.36
3
A
B
(
d, J ¼ 7.1 Hz, 3H ), 1.51 (d, J ¼ 7.1 Hz, 3H ), 3.52 (q, j ¼ 7.1 Hz,
B
A
1
H ), 3.84 (q, j ¼ 7.1 Hz, 1H ) 4.15 (m, 2H þ 2H ), 7.44–7.48
A B A B 3
A
B
A
B
1
3
(
(
(
(
m, 3H þ 3H ), 7.49–7.60 (m, 2H þ 2H ). C NMR (CDCl ) 9.22
B), 9.51 (A), 13.95 (B), 14.16 (A), 61.74 (B), 61.80 (A), 63.76 (B), 65.85
A), 124.65 (A), 125.22 (B), 128.95 (B), 129.20 (A), 131.60 (B), 132.08
A), 140.60 (B), 142.10 (A), 167.84 (B), 168.74 (A). IR (film) 710, 1072,
1
3
097, 1167, 1245, 1328, 1375, 1468, 1746, 2875, 2926, 2961, 2984,
[14]
2
060 cm . Literature data.
1
1
Compound 2qA: H NMR (300 MHz) 1.17

1
776
M. H. Ali et al.
(
t, J ¼ 7.2, 3H), 1.49 (d, J ¼ 7.3, 3H). 3.50 (bq, J ¼ 7.3, 1H), 4.10 (m, 2H),
1
29.149, 131.65, 142. 02, 168.55. Compound 2qB: H NMR (300 MHz)
1
.4–7.75 (m, 5H); C NMR (75 MHz) 9.69, 14.04, 61.86, 65.80, 124.73,
3
7
1
1
4
1
.21 (t, J ¼ 7.2, 3H), 1.32 (d, J ¼ 7.0, 3H), 3.81 (q, J ¼ 7.0, 1H), 4.10 and
1
3
.13 (each 1H, d, J ¼ 7.2, 3.5), 7.4–7.75 (5H); C NMR (75 MHz) 8.93,
4.00, 61.72, 63.68, 125.11, 128.94, 131.74, 140.33, 167.70.
2
-(Sulfinylphenyl)-cyclohexanone (2r) (about 3:l diastereomeric mixture).
1
H NMR (CDCl ) 1.62–2.58 (m, 16H), 3.42 (dd, J ¼ 6 Hz, 10.6H 1H), 3.60
3
1
3
(
dd, J ¼ 7.6 Hz, 1H), 7.46–7.51 (m, 6H), 7.60–7.65 (m, 4H). C NMR
(
CDCl ) 22.72, 2310, 24.05, 24.36, 26.30, 27.90, 42.28, 42.90, 73.04, 73.90,
3
1
2
24.88, 125.27, 128.00, 128.95, 131.13, 131.87, 140.92, 142.20, 205.27,
1
2
05.80. IR (film) 768, 1068, 1104, 1170, 1462, 1718, 2874, 2960, 3072 cm
.
1
-(Sulfinylphenyl) acetophenone (2s). H NMR (CDCl ) 4.34 (d,
2
3
J ¼ 14.1 Hz, 1H), 4.63 (d, J ¼ 14.1, 1H), 7.40–7.56 (m, 7H), 7.60–7.69
1
3
(
m, 1H), 7.80–7.88 (m, 2H). C NMR (CDCl ) 65.75, 124.12, 128.65,
3
1
1
29.22 (2C), 131.45, 134.10, 135.78, 143.22, 191.28. IR (film) 756, 1046,
2
108, 1094, 1267, 1452, 1464, 1684, 2922, 2964, 3010, 3060 cm . Literature
1
[
21] 1
data (200 MHz) ; H NMR 4.29 (d, J ¼ 14, 1H), 4.56 (d, J ¼ 14, 1H), 7.5
(
m, 6H), 7.7 (m, 2H), 7.89 (d, 2H).
1
-Phenyl-2-(phenylsulfinyl)-1-propanone (2t) (diastereomeric mixture). H
1
NMR (CDCl ) 1.34 (d, J ¼ 6.8 Hz, 3H), 1.65 (d, J ¼ 7.20 Hz, 3H), 4.60
3
(
1
q, J ¼ 7.2 Hz, 1H), 4.87 (q, J ¼ 6.80 Hz, 1H), 7.20–7.95 (m, 20H).
3
C NMR (CDCl ) 9.88, 12.50, 66.64, 68.34, 125.40, 125.92, 129.16,
3
1
29.27, 129.32, 129.32, 129.46, 129.64, 132.12, 132.42, 134.40, 134.62,
36.40, 136.92, 140.73, 142.45, 194.92, 196.66. IR ((film) 730, 746, 1080,
1
2
125, 1242, 1324, 1464, 1680, 2882, 2963, 3068 cm . Literature data: H
1
1
1
NMR (100 MHZ)
[
22]
1.32 (d, J ¼ 7 Hz, 1.2H), 1.65 (d, J ¼ 7 Hz, 1.8H),
4
.62 (q, J ¼ 7 Hz, 0.6H), 4.87 (q, J ¼ 7 Hz, 0.4H), 7.10–8.00 (m, 10H).
ACKNOWLEDGEMENT
M.H.A. thanks Bjorn Olesen for help during preparation of this manuscript.
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1
2
3
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5
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7
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Oxidation of Sulfides with N-Bromosuccinimide
1777
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