Synthesis of cetyltrimethylammonium tribromide (CTMATB) and its application in the selective oxidation of sulfides to sulfoxides

Article abstract of DOI:10.1016/S0040-4039(03)01015-3

The bright yellow crystalline cetyltrimethylammonium tribromide (CTMATB) reagent has been synthesized from the reaction of CTMAB and KBr with H₂MoO₄·H₂O, H₂O₂ and H₂SO₄ in the molar ratio 1:2:0.01:4:0.93. CTMATB selectively oxidizes a variety of dialkyl and alkyl aryl sulfides to the corresponding sulfoxides in high yields under mild conditions.

Full text of DOI:10.1016/S0040-4039(03)01015-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4503–4505
Synthesis of cetyltrimethylammonium tribromide (CTMATB)
and its application in the selective oxidation of
sulfides to sulfoxides
Gopa Kar, Anil K. Saikia,* Upasana Bora, Sanjoy K. Dehury and Mihir K. Chaudhuri*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Received 21 March 2003; revised 11 April 2003; accepted 17 April 2003
Abstract—The bright yellow crystalline cetyltrimethylammonium tribromide (CTMATB) reagent has been synthesized from the
reaction of CTMAB and KBr with H2MoO4·H2O, H2O2 and H2SO4 in the molar ratio 1:2:0.01:4:0.93. CTMATB selectively
oxidizes a variety of dialkyl and alkyl aryl sulfides to the corresponding sulfoxides in high yields under mild conditions. © 2003
Elsevier Science Ltd. All rights reserved.
Owing to their importance as intermediates in organic
synthesis1 and their key role in enzyme activation,2
sulfoxides are much sought after. Consequently, selec-
tive oxidation of sulfides to sulfoxides has been a
challenge for many years. Since the first reported syn-
thesis of sulfoxides by Maercker in 1865, a number of
methods have been developed for the transformation of
sulfides to sulfoxides.3 Unfortunately, most of the
methods use hazardous, toxic reagents4 or complex
reaction procedures5 accompanied by overoxidation to
the sulfone or other unwanted side products.6 Molecu-
lar bromine might serve as a good alternative but its
use has been restricted because of it being expensive,
toxic and environmentally unfriendly, and also because
it contaminates the main product with the formation of
side products such as sulfonic acids, sulfinic acids,
bromo substituted sulfides and sulfoxides.7 Extension of
the Br2 oxidation methodology to aromatic sulfides
resulted in the competitive aromatic electrophilic substi-
tution of bromine along with electrophilic attack on
sulfur, thereby affording unwanted products along with
low yields of the target molecules. Sodium metaperio-
date, NaIO4, might be a good choice for the oxidation
of sulfides to sulfoxides8 but for it being prohibitively
expensive. Furthermore, the preparation and recycling
of the reagent are both very difficult. In view of the
above a protocol is required for the selective oxidation
of sulfides to sulfoxides in a clean and cost effective
manner under mild conditions. Most relevantly, recent
work has demonstrated that vanadium bromoperoxi-
dase (VBrPO)9 oxidizes sulfides to sulfoxides in the
presence of hydrogen peroxide wherein the tribromide
−
(Br3 ) formed in situ has been suggested to be responsi-
ble for the sulfide oxidation. Taking cues from this and
being inspired by positive results of the reactivity of a
newly developed tribromide reagent, cetyltrimethyl-
ammonium tribromide (CTMATB),10,11 it was envis-
aged that CTMATB might be suitable for sulfide oxida-
tion (Scheme 1). In this paper the first clean synthesis of
CTMATB is disclosed and its efficacy for the selective
oxidation of sulfides to sulfoxides in very good yields
under mild conditions is reported.
The synthesis12 of the reagent is based on the peroxo-
molybdenum-catalyzed oxidation of bromide to tribro-
−
mide (Br3 ) followed by precipitation with the
cetyltrimethylammonium cation. A peroxomolybdenum
intermediate is generated in situ from the interaction of
2−
MoO4 with H2O2. CTMATB has a very long shelf life
and is environmentally acceptable as a reagent. The
reagent so prepared has been found to oxidize a variety
of sulfides to sulfoxides.13 The reaction is generalized
through entries 1–10 as shown in Table 1.
Keywords: cetyltrimethylammonium tribromide; new reagents; selec-
tive oxidation; sulfoxide.
* Corresponding authors. Tel.: +91 361 2690321-328; fax: +91 361
2690762; e-mail: asaikia@iitg.ernet.in; mkc@iitg.ernet.in
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01015-3

4504
G. Kar et al. / Tetrahedron Letters 44 (2003) 4503–4505
Table 1. Oxidation of sulfides to sulfoxides using
CTMATB
aryl sulfides, which can be understood in terms of the
+I and −I effects of the alkyl and aryl groups, respec-
tively. The +I effect of an alkyl group makes the sulfur
atom more nucleophilic and hence comparatively more
reactive under the present experimental conditions.
In conclusion, we have provided a cleaner synthesis of
a newly developed reagent cetyltrimethylammonium tri-
bromide, CTMATB, based on the oxidation of bromide
by a peroxometal intermediate, and developed a selec-
tive, mild and high yielding method for the oxidation of
sulfides to sulfoxides using CTMATB as the oxidizing
agent. Under these conditions functional groups such
as hydroxyl and acetate remain unaffected.14 The by-
product cetyltrimethylammonium bromide (CTMAB)
can be recycled to give CTMATB thereby rendering the
protocol economic. The results obtained so far suggest
that the new reagent is highly suitable for the selective
transformation of sulfides to sulfoxides, which is other-
wise rather difficult to achieve, and also that the proto-
col might serve as a method for similar types of
oxidations.
Acknowledgements
1
The authors thank CDRI, Lucknow for providing H
NMR and mass spectra.
References
Against the backdrop of the reagent acting as a bromi-
nating agent10b for aromatics and olefins as well as a
deprotecting agent11a for dithioacetals and as a protect-
ing/deprotecting agent for carbonyl-1,3-oxathiolane
interconversion, it is believed that the active species in
these reactions is molecular bromine generated in situ
which in turn acts as an electrophile. Importantly, the
amount of the active species can be tuned by regulating
the amount of reagent, an operation that is rather
difficult in the direct use of liquid bromine or a bromine
solution. An electrophilic attack of bromine on sulfur
then leads to the intermediate [A], which is then
hydrolyzed by water to give the corresponding sulfox-
ide as shown in Scheme 2.
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Scheme 2.

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room temperature for 12 h. The reaction was monitored
by TLC and GC and no overoxidation was detected. On
completion of the reaction, acetonitrile was removed
under reduced pressure and 7 mL of water added. The
product was extracted with ethyl acetate, dried over
Na2SO4 and then evaporated to dryness, while the
aqueous layer was retained for recovery of CTMAB. In
order to remove any traces of CTMAB, the product was
transferred to a silica gel (60–120 mesh) column and
eluted with ethyl acetate: hexane (1:8). Methyl phenyl
12. Synthesis of cetyltrimethylammonium tribromide: A solu-
tion of 5.2 g (43.7 mmol) of KBr in 20 mL (20 mmol) of
1 M H2SO4 was added to a clear light yellow solution of
0.04 g (0.22 mmol) of H2MoO4·H2O in 10 mL (88.2
mmol) of 30% H2O2. The resulting solution was then
added to a solution of 7.9 g (21.7 mmol) of CTMAB in
75 mL of water in portions with stirring to afford a deep
yellow solution. This was stirred for ca. 2 h in an ice bath
and then the bright yellow colored crystalline CTMATB
which had precipitated was separated by suction filtra-
tion, washed three or four times with ice cold water (12
mL) and finally dried in vacuo over fused CaCl2. The
yield was 9.9 g (87%) and the compound analyzed; mp
87–88°C (DSC onset 87°C); UV–vis: 269, 385 nm; IR:
1
sulfoxide was isolated as a liquid in 93% yield. H NMR
(300 MHz, CDCl3): l 2.73 (s, 3H, -CH3), 7.55 (m, 3H,
aromatic), 7.64 (m, 2H, aromatic). IR: 2989, 1091, 1051
cm−1; ESMS: (M++1) 141. The aqueous layer containing
CTMAB was concentrated by evaporation until a white
crystalline compound was obtained. The CTMAB thus
recovered was recycled to CTMATB following the
described procedure.12
14. (a) n-Pentyl-2-hydroxyethyl sulfoxide: 1H NMR (300
MHz): l 0.92 (t, J=6.9 Hz, 3H, -CH3), 1.41 (m, 4H,
2-CH2-), 1.77 (m, 2H, -CH2-), 2.89 (m, 4H, -CH2SOCH2-
), 4.10 (m, 2H, -CH2-O-); IR: 3370, 2965, 2924, 2868,
1475, 1024, 1034, 748 cm−1; ESMS: (M++1) 165.
(b) 2-Ethylsulfinylethyl acetate: 1H NMR (300 MHz): l
1.38 (t, J=7.38 Hz, 3H, -CH3), 2.10 (s, 3H, CH3CO-),
2.78 (m, 2H, -CH2SO-), 2.95 (m, 2H, -CH2SO-), 4.51 (m,
2H, -CH2-OAc); IR: 3370, 2965, 2924, 2868, 1475, 1024,
1034, 748 cm−1; ESMS: (M++1) 165.
1
203s (nas, Br-Br), 152s (ns, Br-Br); H NMR (300 MHz,
CDCl3): l 0.88 (t, J=6.8 Hz, 3H, -CH3), 1.27 (m, 28H,
-CH2-), 1.67 (m, 2H, -CH2-), 3.36 (s, 9H, 3 -N-CH3), 3.49
(t, J=8.4 Hz, 2H, -N-CH2-). Anal. calcd for C19H42Br3N:
C, 43.53; H, 8.08; N, 2.67. Found: C, 43.09; H, 7.99; N,
2.74.
13. General procedure for the oxidation of sulfides to sulfox-
ides: Methyl phenyl sulfide (0.21 g, 1.69 mmol) in a mixed
acetonitrile (2 mL)–water (1 mL) solvent was reacted
with CTMATB (1.06 g, 2.02 mmol) under stirring at