Synthesis of dimethyl aryl acylsulfonium bromides from aryl methyl ketones in a DMSO-HBr system

Article abstract of DOI:10.3390/molecules181215717

A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO). This sulfonium salt confirms that bromine production and the bromination reaction take place in the DMSO-HBr oxidation system. What's more, it is also a key intermediate for the synthesis of arylglyoxals.

Full text of DOI:10.3390/molecules181215717

Molecules 2013, 18, 15717-15723; doi:10.3390/molecules181215717
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molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis of Dimethyl Aryl Acylsulfonium Bromides from
Aryl Methyl Ketones in a DMSO-HBr System
Zhiling Cao 1,*, Dahua Shi 2, Yingying Qu 2, Chuanzhou Tao 2, Weiwei Liu 2 and Guowei Yao 3
1
Jiangsu Key Laboratory of Marine Biotechnology, Jiangsu Institute of Marine Resources,
Huaihai Institute of Technology, Lianyungang 222005, China
2
School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang 222005, China
3
School of Life Science, Beijing Institute of Technology, Beijing 100081, China
* Author to whom correspondence should be addressed; E-Mail: zhilingcao2013@163.com;
Tel./Fax: +86-518-8589-5408.
Received: 26 November 2013; in revised form: 10 December 2013 / Accepted: 10 December 2013 /
Published: 16 December 2013
Abstract: A new, simplified method for the synthesis of dimethyl aryl acylsulfonium salts
has been developed. A series of dimethyl aryl acylsulfonium bromides were prepared by
the reaction of aryl methyl ketones with hydrobromic acid and dimethylsulfoxide (DMSO).
This sulfonium salt confirms that bromine production and the bromination reaction take
place in the DMSO-HBr oxidation system. What’s more, it is also a key intermediate for the
synthesis of arylglyoxals.
Keywords: dimethyl aryl acylsulfonium; aryl methyl ketones; DMSO-HBr; synthesis;
arylglyoxals
1. Introduction
In 1957, Kornblum first reported oxidation of α-bromoketones into α-ketoaldehydes by
dimethylsulfoxide (DMSO) [1]. Schipper also found that 1,3-diketones could be directly oxidized to
1,2,3-trione derivatives in a DMSO-HBr system [2]. This method has been modified by Folyd and
applied to the preparation of aryldiketone (arylglyoxal) derivatives from arylmethyl ketones in high
yield [3]. Aryldiketones and arylglyoxals are important building blocks in organic synthesis, particular
in the synthesis of biologically active phenylimidazoles, oxazoles, and quinolines [4–7].

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The DMSO-HBr system has been proved to be extremely efficient for the oxidation of the α-methyl
group of arylketones [8]. Compared with the traditional selenium dioxide oxidation [9], DMSO-HBr
oxidation is milder, less toxic and easy to perform. Furthermore, arylalkynes and alkenes were found
to be suitable as substrates for this oxidation system [10,11].
However, when we tried to prepare arylglyoxals 2 from aryl methyl ketones 1 with the DMSO-HBr
oxidation system in a sealed flask, we observed that aryl acylsulfonium bromides 3 were unexpectedly
produced (Scheme 1). Sulfonium salts, characterized by low sulfur valence and relatively unstable
carbon-sulfur bonds, are very useful in practical applications [12]. For example, dimethyl
phenacylsulfonium salts can form stable sulfur ylides, which have aroused great interest among
researchers [13–15]. David recently reported the synthesis of trisubstituted cyclopropanes by
condensation of sulfonium ylides with α,β-unsaturated aldehydes [16]. Aryl acylsulfonium bromides
can also be used to synthesize 1,4-dicarbonyl compounds by condensation with arylglyoxals [17].
Acylsulfonium bromide salts are normally prepared from dimethyl sulfide and an α-bromoketone.
In this study, we report a new and efficient route to aryl acylsulfonium salts and α-bromoacylsulfonium
salts from aryl methyl ketones using the DMSO-HBr oxidation system.
Scheme 1. Reaction of aryl methyl ketones in the DMSO-HBr system.
Sulfonium salts 3 have never been reported as key intermediate products in DMSO-HBr oxidations
of arylmethyl ketones. The formation of salt 3 confirms that the production of bromine and the
bromination reaction take place in the DMSO-HBr system. Catalytic oxidation of methyl ketones
by vinyl bromide in DMSO is another piece of evidence to support this approach [18]. The mechanism
of DMSO-HBr mediated oxidation is still under intense and controversial discussion. Sulfonium
salt 3 provides a new basis and reference mechanism for the oxidation of methyl ketones in
DMSO-HBr system.
2. Results and Discussion
The transformation of aryl acetones 1a–h into sulfonium salts 3a–h in moderate yields (48%–75%,
Table 1) was achieved in a mixture of 48% hydrobromic acid (HBr) and DMSO in a sealed flask over
10 h. White solid precipitates could be collected after addition of ether and ethyl acetate to the reaction
mixtures. These crystalline solids were readily soluble in water, but insoluble in organic solvents.
1
13
The H- and C-NMR spectra of the products clearly indicated the formation of the sulfonium salt
derivatives. Various substituents at the aromatic ring have been shown to affect the yields of the

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final products. What’s more, in the case of aryl acetones 3e–h, α-bromoacylsulfonium salt products
were obtained.
Table 1. Synthesis of dimethyl aryl acylsulfonium bromides 3a–h.
Entry
Aryl Acetone
Product
Yield (%)
a
69
b
c
57
71
O
O
S
Br
Br
Br
d
e
62
75
f
55
57
48
g
h
Table 2 collects data on the reaction of acetophenone (1a) with DMSO-HBr under different
experimental conditions. It is revealed that the reaction time and temperature were very crucial for the
synthesis of 3. An increased molar ratio of HBr not only increases the yield, but also shortens the
reaction time. We thus obtained the best results using 3 equiv. of HBr (aq 48%) at 40 °C in the
presence of DMSO (Table 2, entry 2).
The proposed mechanism for the synthesis of acylsulfonium bromides 3 is shown in Scheme 2.
First, oxidation of HBr with DMSO results in the formation of molecular bromine, which reacts with
the arylacetone 1 to form the α-bromoketone 4a and α-dibromoketone 4b. In addition, dimethyl sulfide
is also produced in this oxidation step. The whole reaction is performed in a sealed flask to minimize
the escape of dimethyl sulfide which on condensation with bromoketones 4a and 4b affords the
sulfonium salt 3.

Molecules 2013, 18
Table 2. Optimization of reaction conditions for synthesis of sulfonium salt 3a a.
15720
Molar Ratio
Methyl Ketone/HBr
Entry
Time (h)
Temp. (°C)
Yield (%)b
1
2
3
4
5
6
1:3
1:3
1:3
1:3
1:1
1:5
6
40
40
40
55
40
40
41
69
56
45
12
61
10
12
10
12
6
a All reactions were heated in a sealed flask containing the same volume of DMSO; b Isolated yields.
Scheme 2. Mechanism for the formation and decomposation of acylsulfonium bromide 3.
The oxidation of aryl methyl ketones with DMSO is complicated and two mechanisms were
proposed recently in the literature. According to the Kornblum reaction, α-bromoketone 4a is rapidly
converted into arylglyoxal 2 through an alkoxydimethyl sulfonium intermediate 5 [8]. Floyd et al. have
suggested that the hydrolysis and bromination of α-bromoketone 4a gives an α-hydroxy-α-bromo
intermediate, which is hydrolyzed to glyoxal 2 [3]. In the present paper, sulfonium salt 3 exists in the
DMSO-HBr oxidation system. The above observations suggest that sulfonium salt 3 is also a key
intermediate for synthesis of glyoxal 2, and it would be decomposed to α-bromoketone 4a and
α-dibromoketone 4b by heating in an open system. As shown in Scheme 2, both the reaction of 4a with
DMSO and the hydrolysis of 4b yield the same product 2. Sulfonium salt 3 is soluble in water and
DMSO, and its conversion is very rapid in an open system. In this study, a series of acylsulfonium
bromide salts were successfully synthesized by controlling the reaction conditions and precipitation
using ether and ethyl acetate.
3. Experimental
3.1. General
All reagents for synthesis were purchased from TCI Shanghai Co. (Shanghai, China) unless
otherwise specified. Melting points were measured on an XT-4 melting point apparatus (Beijing Tech
Instrument, Beijing, China) and are uncorrected. NMR spectra were measured using a Bruker AQS
AVANCE 300 MHz spectrometer ((Bruker Instruments, Karlsruhe, Germany) with tetramethylsilane

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as the internal standard. Mass spectra were recorded with an Agilent Technologies MSD SL Trap mass
spectrometer (Agilent Technologies, Palo Alto, CA, USA) with an ESI source coupled with an 1100
Series HPLC system. Silica gel GF254 plates (Yantai Chemical Industrials, Yantai, China) was used
for thin-layer chromatography (TLC). UV light (λ 254 nm) detection was used.
3.2. General Procedure for the Synthesis of Sulfonium Salts 3a–h
Aryl methyl ketones 1a–h (39.5 mmol) were dissolved in a mixture of 48% hydrobromic acid
(20 mL) and dimethylsulfoxide (20 mL) in a sealed flask. This mixture was heated at 40 °C for 10 h
and then cooled. After the addition of ethyl acetate (15 mL) and ethyl ether (15 mL), the solution was
stirred for another 0.5 h and allowed to stand overnight in the ice box. The precipitate was filtered and
washed with ethyl ether to afford the desired sulfonium salt as white crystals.
Dimethylphenacylsulfonium bromide (3a). Yield: 69%, mp 145–147 °C (lit. [3] 148–152 °C). 1H-NMR
(DMSO-d6) δ 8.03 (d, 2H, J = 7.5 Hz, Ar-H), 7.8 (t, J = 7.4 Hz, 1H, Ar-H), 7.64 (t, J = 7.7 Hz, 2H,
Ar-H), 5.53 (s, 2H, CH2), 2.99 (s, 6H，2CH3); 13C-NMR (DMSO-d6) δ 191.37, 133.96, 135.09, 129.22,
128.70, 52.88, 24.63; MS (ESI) m/z: 180.9 [C10H13OS]+.
1
Dimethyl-(4-hydroxylphenacyl)sulfonium bromide (3b). Yield: 57%, mp 151–152 °C. H-NMR
(DMSO-d6) δ 10.83 (s, 1H, OH), 7.90 (d, J = 8.7 Hz, 2H, Ar-H), 6.94 (d, J = 8.7 Hz, 2H, Ar-H), 5.41
(s, 2H, CH2), 2.95 (s, 6H, 2CH3); 13C-NMR (DMSO-d6) δ 189.21, 163.84, 131.58, 125.40, 115.84,
52.68, 24.57. MS (ESI) m/z: 197.2 [C10H13O2S]+; Anal. calcd. for C10H13BrO2S: C, 43.33; H, 4.73.
Found: C, 43.19; H, 4.62.
Dimethyl-(3-bromophenacyl)sulfonium bromide (3c). Yield: 71%, mp 142–143 °C. 1H-NMR (DMSO-d6)
δ 8.20 (s, 1H, Ar-H), 8.01 (t, J = 7.8 Hz, 2H, Ar-H), 7.61 (t, J = 7.9 Hz, 1H, Ar-H), 5.52 (s, 2H, CH2),
13
2.98 (s, 6H, 2CH3); C-NMR (DMSO-d6) δ 190.54, 137.53, 136.02, 131.46, 131.31, 127.59, 122.44,
52.73, 24.74. MS (ESI) m/z: 259.1 [C10H12BrOS]+; Anal. calcd. for C10H12Br2OS: C, 35.32; H, 3.56.
Found: C, 35.25; H, 3.43.
Dimethyl-(furan-2-acyl)sulfonium bromide (3d). Yield: 62%, mp 132–135 °C. 1H-NMR (DMSO-d6) δ
8.21 (d, J = 1.1 Hz, 1H, Ar-H), 7.74 (d, J = 3.7 Hz, 1H, Ar-H), 6.87 (dd, J = 3.7, 1.6 Hz, 1H, Ar-H),
5.28 (s, 2H, CH2), 3.00 (s, 6H, 2CH3); 13C-NMR (DMSO-d6) δ 178.64, 149.99, 149.58, 121.96,
113.51, 50.70, 24.70. MS (ESI) m/z: 171.2 [C8H11O2S]+; Anal. calcd. for C8H11BrO2S: C, 38.26; H,
4.41. Found: C, 38.34; H, 4.58.
Dimethyl-(a-bromo-4-methylphenacyl)sulfonium bromide (3e). Yield: 75%, mp 144–145 °C. 1H-NMR
(DMSO-d6) δ 7.99 (d, J = 7.8 Hz, 2H, ArH), 7.86 (s, 1H, CH), 7.47 (d, J = 7.8 Hz, 2H, Ar-H), 3.07
(s, 3H, SCH3), 3.01 (s, 3H, SCH3), 2.44 (s, 3H, Ar-CH3); 13C-NMR (DMSO-d6) δ 188.74, 146.83,
129.96, 129.33, 128.76, 56.20, 24.71, 24.63, 21.51. MS (ESI) m/z: 273.2 [C11H14BrOS]+; Anal. calcd.
for C11H14Br2OS: C, 37.31; H, 3.99. Found: C, 37.39; H, 4.13.
1
Dimethyl-(a-bromo-4-nitrophenacyl)sulfonium bromide (3f). Yield: 55%, mp 138–139 °C. H-NMR
(DMSO-d6) δ 8.49 (d, J = 8.9 Hz, 2H, Ar-H), 8.30 (d, J = 8.8 Hz, 2H, Ar-H), 7.94 (s, 1H, CH), 3.07

Molecules 2013, 18
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13
(s, 3H, SCH3), 3.03 (s, 3H, SCH3); C-NMR (DMSO-d6) δ 190.73, 151.03, 136.27, 131.17, 124.34,
56.33, 24.75; MS (ESI) m/z: 304.2 [C10H11BrNO3S]+; Anal. calcd. for C10H11Br2NO3S: C, 31.19; H,
2.88. Found: C, 31.25; H, 2.71.
Dimethyl-(a-bromo-4-chlorophenacyl)sulfonium bromide (3g). Yield: 57%, mp 152–153 °C. 1H-NMR
(DMSO-d6) δ 8.09 (d, J = 8.5 Hz, 2H, Ar-H), 7.83 (s, 1H, CH), 7.78 (d, J = 8.5 Hz, 2H, Ar-H), 3.06
13
(s, 3H, SCH3), 3.00 (s, 3H, SCH3); C-NMR (DMSO-d6) δ 188.23, 140.63, 131.61, 130.14, 129.60,
56.25, 24.65; MS (ESI) m/z: 293.2 [C10H11BrClOS]+; Anal. calcd. for C10H11Br2ClOS: C, 32.07; H,
2.96. Found: C, 32.15; H, 2.85.
1
Dimethyl-(a-bromo-4-fluorophenacyl)sulfonium bromide (3h). Yield: 48%, mp 141–143 °C. H-NMR
(DMSO-d6) δ 8.17 (dd, J = 8.8, 5.4 Hz, 2H, Ar-H), 7.77 (s, 1H, CH), 7.54 (t, J = 8.8 Hz, 2H, Ar-H),
3.05 (s, 3H), 2.98 (s, 3H); 13C-NMR (DMSO-d6) δ 190.12, 166.05 (d, J = 254.5 Hz), 131.96 (d,
J = 10.0 Hz), 130.83 (d, J = 2.8 Hz), 116.46 (d, J = 22.3 Hz), 52.82, 24.71; MS (ESI) m/z: 277.1
[C10H11BrFOS]+; Anal. calcd. for C10H11Br2FOS: C, 33.54; H, 3.10. Found: C, 33.46; H, 3.21.
4. Conclusions
In conclusion, the combination DMSO and aqueous HBr has been utilized here for the efficient
synthesis of dimethyl aryl acylsulfonium bromides from aryl methyl ketones under mild reaction
conditions. In some cases, α-bromoacylsulfonium salt products were obtained.
Acknowledgments
The work described in this paper was supported by the Natural Science Research Foundation of the
Jiangsu Higher Education Institutions (13KJB150006, 12KJB35001, 10KJA170003), the PAPD
Program (A Project Funded by the Priority Academic Program Development of Jiangsu Higher
Education Institutions), the Open-ended Funds of Jiangsu Key Laboratory of Marine Biotechnology
(2011HS001) and the Open-ended Funds of Jiangsu Marine Resources Development Research Institute
(No. JSIMR201204).
Conflicts of Interest
The authors declare no conflict of interest.
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