Dramatic influence of ionic liquid and ultrasound irradiation on the electrophilic sulfinylation of aromatic compounds by sulfinic esters

Article abstract of DOI:10.3390/molecules22091458

The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic esters as electrophiles has been investigated in different ionic liquids and by means of different Lewis acid salts in order to get moderate to good yields of asymmetrical

Full text of DOI:10.3390/molecules22091458

molecules
Article
Dramatic Influence of Ionic Liquid and Ultrasound
Irradiation on the Electrophilic Sulfinylation of
Aromatic Compounds by Sulfinic Esters
Ngoc-Lan Thi Nguyen 1, Hong-Thom Vo 1, Fritz Duus 2 and Thi Xuan Thi Luu 1,
*
1
Department of Organic Chemistry, VNUHCM-University of Science, 227 Nguyen Van Cu St., Dist. 5,
700000 Ho Chi Minh City, Vietnam; lanbmt07@gmail.com (N.-L.T.N.); hongthom2012@gmail.com (H.-T.V.)
Department of Science and Environment, Roskilde University, P.O. Box 260, DK-4000 Roskilde, Denmark;
fd@ruc.dk
2
*
Correspondence: ltxthi@hcmus.edu.vn; Tel.: +84-0208-3835-3193
Received: 12 August 2017; Accepted: 28 August 2017; Published: 4 September 2017
Abstract: The sulfinylation reaction of aromatic and hetero-aromatic compounds with sulfinic
esters as electrophiles has been investigated in different ionic liquids and by means of different
Lewis acid salts in order to get moderate to good yields of asymmetrical sulfoxides. Mixtures of
1-butyl-3-methylimidazolium chloride and aluminum chloride were found to be the most efficient
and recyclable reaction framework. Ultrasound sonication appeared to be the most useful and green
activation method to afford the sulfoxides in yields better than or equivalent to those obtained under
the longer-lasting conventional stirring conditions.
Keywords: Friedel-Crafts sulfinylation; sulfinic ester; synthesis of sulfoxide; ultrasound irradiation;
chloroaluminate-based ionic liquid
1. Introduction
Sulfoxides are important intermediates in organosulfur chemistry, especially in the syntheses of
drugs and sulfur-containing natural products [
psychotonics [ ], vasodilators [ ], and therapeutic agents for anti-ulcer (proton pump inhibitor) [
antibacteria, antifungi, or anti-atherosclerosis [13–17], and antihypertension [18].
1
]. Sulfoxides are also used as cardiotonic agents [
2],
3
,
4
5
6–
12],
The importance of sulfoxides in organic syntheses has attracted the attention of chemists to find
new methodologies for sulfoxide synthesis. Aliphatic and aromatic sulfoxides have been prepared
by the direct and popular oxidation of thioethers [19,20], by indirect reduction of sulfones [21], or by
nucleophillic interaction of Grignard reagents on sulfinic esters [22,23], and sulfoxides [24].
Symmetrical aromatic sulfoxides can also be obtained by reaction of arenes with thionyl
chloride [25,26], as well as symmetrical/asymmetrical aromatic sulfoxides can be prepared by
sulfinylation of aromatic compounds, as described aldready in 1926 [27]. More than thirty
years later, alkanesulfinylation and arenesulfinylation of aromatic compounds, (e.g., benzene,
azulene/guaiazulene, substituted phenols, and aniline derivatives) with alkanesulfinyl or arenesulfinyl
chlorides as electrophiles were investigated in the presence of pyridine [28], anhydrous aluminium
chloride [29
–
31], as well as SnCl4 or SbCl5 [30]; however, owing to the easy decomposition of
30]. Very recently a replacement
the sulfinyl halides, harsh reaction conditions were required [28
–
of the sulfinyl halides by more stable electrophiles, i.e., sulfinic esters, was introduced in 2011
by Yuste et al. [32]. In connection with the synthesis of (phenylsulfinyl)phenols, the Thia-Fries
rearrangement of aryl benzenesulfinate in the presence of aluminum chloride has been studied [33].
The ionic liquid ethylammonium nitrate was synthesized already in the early 1910s [34].
Subsequently, research and development of ionic liquid has concentrated mainly on electrochemical
Molecules 2017, 22, 1458; doi:10.3390/molecules22091458
www.mdpi.com/journal/molecules

Molecules 2017, 22, 1458
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applications since 1948 [35]. In the early 1980s ionic liquids (ILs) attained much more attention
owing to their unique chemical and physical properties of non-volatility, non-flammability, thermal
stability, and controlled miscibility [35,36]. They have been also used as green solvents in various
biphasic ILs-transition metal-catalyzed organic reactions in order to improve catalyst storage, handling,
recycling and reuse. The first successful combination of an ionic liquid, dialkylimidazolium chloride,
with aluminum chloride used as a Lewis acid catalyst in Friedel-Crafts acylations was reported in
1986 [37].
One of viewpoints on green chemistry, ultrasound irradiation has been regarded as a clean and
useful protocol during the last three decades in comparison with traditional activation methods. Many
categories of homogeneous or heterogeneous reactions accelerated by ultrasound irradiation have
been launched in order to reduce the reaction time, and generate fewer byproducts and a higher yield
of the main product [38,39].
In this present work, we integrate the advantages of ultrasound irradiation accelerated
sulfinylation of arenes and hetero-arenes with stable alkyl alkanesulfinates/arenesulfinates in the
presence of different acidic catalysts to produce asymmetrical sulfoxides (Scheme 1). Several Lewis
acid salts as well as a task-specific ionic liquid and the mixtures of 1-butyl-3-methyl-imidazolium
chloride and different Lewis acid salts with different Lewis acidity were investigated.
R3
R3
R1
R4
R4
R3
R3
S
O
O
R1
R1
Lewis acidic catalyst
r.t
S
R1
O
R2
S
+
O
S
+
R2
O
H
)))),
O
N
R4
N
R4
O
S
R1
X
X
R1 = C2H5, i-C3H7, n-C8H17, C6H5, p-CH3C6H4, p-CH3OC6H4
R2 = CH3, C2H5, n-C3H7
R3 = H, OCH3, OH, N(CH3)2
R4 = H, CH3, OCH3
X = C, S
Scheme 1. Synthesis of sulfoxides from alkyl alkanesulfinate/arenesulfinate via the sulfinylation reaction.
2. Results
Based on the previous literature and the points of view on green chemistry, a series of
Lewis acid salts, for instance bismuth(III) triflate, lanthanide(III) triflate, and copper(II) triflate
were used as the acidic catalysts for the solvent-free sulfinylation of 1,3-dimethoxybenzene (our
arbitrarily-chosen model substrate) by methyl benzenesulfinate under ultrasound irradiation in
order to compare with aluminum chloride catalyst (Entries 1–4, Table 1). The results showed
that aluminum chloride efficiently catalyzed the sulfinylation of 1,3-dimethoxybenzene into
2,4-dimethoxy-1-(phenylsulfinyl)benzene under solvent-free as well as solvent reaction condition
(Entry 5, Table 1); however, the product selectivity of 2,4-dimethoxy-1-(phenylsulfinyl)benzene
reported by GC/MS analyses was achieved 60% from the solvent-free sulfinylation lower than 88%
from the solvent sulfinylation owing to severe demethylation of methoxy substituent on aromatic ring.
In addition, it is not safe to add anhydrous aluminum chloride directly into the reaction mixture due
to the large exotherm.
On the way to find out a green and recyclable acidic catalyst, a series of ionic liquids (Entries -6–12,
Table 1), e.g., a task-specific ionic liquid, 1-methyl-3-(4-sulfobutyl)imidazolium hydrogen sulfate,

Molecules 2017, 22, 1458
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[(HSO3)4C4C1Im]HSO4, an eutectic mixture of choline chloride and zinc chloride as well as the
mixture of [Bmim]Cl and several Lewis acid salts were investigated. The results substantiate our
choice of chloroaluminate-based 1-butyl-3-methylimidazole chloride as the most efficient catalyst
under ultrasound irradiation. Owing to the mild and efficient catalysis of chloroaluminate-based
1-butyl-3-methylimidazole chloride, demethylation of methoxy substituted group was not found by
GC/MS analyses and thin layer chromatography (TLC) during the reaction period.
The composition of chloroaluminate-based ionic liquids is expressed as the apparent AlCl3
mole fraction (N) in order to vary their Lewis acidity. They are classified into three types such
as base liquids, neutral liquids and acidic liquids [37
mole fraction (Entries 12–14, Table 1) demonstrated that [Bmim]Cl
(1-butyl-3-methylimmidazole combined with twice molar amount of aluminum chloride, N = 0.67)
promoted the sulfinylation of 1,3-dimethoxybenzene to take place most efficiently.
,
40]. Further experiments on the AlCl3
2AlCl3 or [Bmim][Al2Cl7]
·
Table 1. Influence of the nature of the acidic catalyst on the formation of 2,4-dimethoxy-1-
(phenylsulfinyl)benzene (3a) a.
MeO
OMe
MeO
OMe
O
Acidic catalyst
r.t
S
+
+
MeOH
Ph
)))),
S
O
O
1a
2a
3a
Yield b (%)
Entry
Acidic Catalyst (mmol)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Bi(OTf)3(0.05), solvent-free
La(OTf)3(0.05), solvent-free
Cu(OTf)2(0.05), solvent-free
AlCl3(2.0), solvent-free
3
-
-
16
7
6
-
3
4
-
AlCl3(2.0) in 1,2-dichloroethane (1 mL)
[(HSO3)4C4C1Im]HSO4(1.0)
[Choline]Cl·3ZnCl2 (1.0)
[Bmim]Cl·2ZnCl2 (1.0)
[Bmim]Cl·2ZnCl2 (1.2)
[Bmim]Cl·2NiCl2(1.0)
[Bmim]Cl·p-TSA (2.0)
[Bmim]Cl·AlCl3(1.0)
-
32
55
25
69
72
68
[Bmim]Cl·2AlCl3(1.0)
[Bmim]Cl·3AlCl3(1.0)
[Bmim]Cl·2AlCl3(1.1)
[Bmim]Cl·2AlCl3(1.2)
[Bmim]Cl·2AlCl3(1.5)
a
The reactions of 1,3-dimethoxybenzene (1 mmol) with methyl benzenesulfinate (1 mmol) catalyzed by the acidic
catalysts were performed under ultrasound irradiation for one hour at room temperature; b Yield of isolated product.
In order to improve the reaction conversion and yield of sulfoxide, the molar ratio of
[Bmim]Cl 2AlCl3, 1,3-dimethoxybenzene, methyl benzenesulfinate was investigated (Entries 15–17,
·
Table 1). Subsequently, the other reaction factors consisting of reaction temperatures (e.g., room
temperature, 50 ◦C and 60 ◦C), the reaction time, and the activation methods (e.g., magnetic stirring,
ultrasound irradiation and microwave irradiation) were also studied. Consequently, the most efficient
procedure for the sulfinylation of 1,3-dimethoxybenzene (1 mmol) with methyl benzenesulfinate
(1 mmol) in the appropriate amount of [Bmim]Cl 2AlCl3 (1.2 mmol) performed under ultrasound
·
irradiation for one-hour at room temperature was selected (Entry 1, Table 2). Further experiments
showed that the highest yield of 2,4-dimethoxy-1-(phenylsulfinyl)benzene was achieved up to 72%
after one-hour ultrasound irradiation, while it was 69% after four-hour magnetic stirring. In addition,
microwave irradiation is not an efficient method for this reaction owing to the decomposition of
reaction mixture at warm temperature (approx. 50 ◦C).

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The optimized conditions were used to investigate the substrate scope of the sulfinylation.
Altogether ten aromatic and hetero-aromatic compounds were subjected to [Bmim]Cl 2AlCl3-catalysed
·
electrophilic sulfinylation by eight alkyl alkanesulfinate/arenesulfinates under ultrasound irradiation
(Tables 2 and 3).
Table 2. Influence of the nature of the alkyl alkane/arenesulfinates on the yields of asymmetrical
sulfoxides a.
MeO
OMe
MeO
OMe
R1
O
[Bmim]Cl⋅2AlCl3
r.t
R2
S
+
R2OH
+
R1
S
)
))),
O
O
1 (a-f)
2a
3 (a-f)
Yield b (%)
Entry
Sulfinic Ester
Product
Time (h)
MeO
OMe
O
S
1.0
1.5
72
73
O
1
3a
S
O
O
S
2
3
4
O
1.0
1.0
72
77
O
S
O
MeO
OMe
O
S
1.0
4.0
15
70
3b
3c
S
O
O
MeO
OMe
1.0
4.5
10
68
O
S
5
6
S
O
O
MeO
OMe
O
1.0
4.0
17
72
S
5
3d
S
5
O
O
MeO
OMe
O
S
O
7
8
3e
3f
1.0
1.0
73
75
S
O
MeO
OMe
O
OMe
S
O
S
O
O
a
The reactions of 1,3-dimethoxybenzene (1 mmol) with sulfinic ester (1 mmol) catalyzed by [Bmim][Al2Cl7]
(1.2 mmol) were performed under ultrasound irradiation for a specific period of time (in hours) at room temperature;
b
Yield of isolated product.
The results from altering eight alkyl alkanesulfinate/arenesulfinates used for the sulfinylation of
1,3-dimethoxybenzene demonstrated that the structures of sulfinic esters have influenced the reaction
conversion and yield significantly (Table 2). Alkyl arenesulfinates appeared as better electrophiles than
alkyl alkanesulfinates. It was, therefore, concluded that the aromatic ring played an important role to
stabilize electrons of intermediate in the transition stage (Discussion, Scheme 2).

Molecules 2017, 22, 1458
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Table 3. Influence of the nature of the aromatic compounds on the sulfinylation using methyl
benzenesulfinate a.
Yield b (%)
Entry
Arene
Product
Time (h)
OMe
OMe
1
3g
3h
1.0
61
68
S
O
OMe
OMe
OMe
OMe
2
3
1.0
1.0
S
O
HO
Me
Me
OH
Me
OH
S
S
75
O
O
11 (3i)
89 (3i′)
Me
N
Me
N
Me
4
5
6
Me
3j
3k
3l
1.0
2.0
3.0
81
58
53
S
O
OMe
OMe
S
O
MeO
OMe
S
O
Me
N
7
3m
0.5
73
N
S
Me
O
H
N
8
9
3n
3p
3q
0.5
8
40
13
6
N
H
S
O
O
S
S
S
10
8
S
O
a
The reactions of arene (1 mmol) with methyl benzenesulfinate (1 mmol) catalyzed by [Bmim][Al2Cl7] (1.2 mmol)
were performed under ultrasound irradiation for a specific period of time (in hours) at room temperature; b Yield of
isolated product.

Molecules 2017, 22, 1458
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R1
O
R1
Cl
R2
S
[Bmim][Al2Cl6OR2]
+
+
[Bmim][Al2Cl7]
S
O
O
(A)
R3
R3
H
R4
R1
R1
Cl
Cl
R1 S O
R1
[Bmim][Al2Cl7]
+
S
R4
S
S
- Cl
- AlCl3
- [Bmim]AlCl4
O
O
(C)
O
(D)
AlCl3
(B)
- H
R3
R1
S
R4
O
[Bmim][Al2Cl7]
[Bmim][AlCl4]
AlCl3
+
R2OH
[Bmim][Al2Cl6OR2]
+
+
+
[Bmim][Al2Cl7]
Cl
+
2 [Bmim][Al2Cl7]
H
Scheme 2. A plausible mechanism for the sulfinylation of aromatic compounds with alkyl
arenesulfinates using [Bmim][Al2Cl7].
In the next series of experiments on the influences of substituted benzene or substituted polycyclic
benzenoid hydrocarbons, benzene, naphthalene and phenanthrene were selected as model substrates.
The results displayed that the reactions of benzene and naphthalene with methyl benzenesulfinate did
not occur, while the reaction of phenanthrene worked slowly to obtain a low yield of sulfoxide (4%)
under ultrasound irradiation for three hours. Further experiments on the electrophilic sulfinylation of
electron rich arenes with methyl benzenesulfinate demonstrated that sulfoxide products were obtained
in moderate to good yield after much shorter reaction times (generally 1 h) under ultrasound irradiation,
especially most sulfinyl groups were predominantly located at para position compared with the former
activating substituents on aromatic substrates in order to reduce the steric hindrance (Entries 1–6,
Table 3). Contrarily, a sulfinyl group was favorably occupied at the ortho position compared with
hydroxyl group in order to reach a lower transition free energy and more stable product from the
formation of intra-hydrogen bond between hydroxyl group and sulfinyl group (Entry 3, Table 3).
In the continuation of substrate investigation, the reactions of indole derivatives and methyl
benzenesulfinate showed that the amount of sulfoxide formed from the sulfinylation of indole was
obtained in a lower yield than it from the sulfinylation of 1-methylindole due to a complex formation
between indole and [Bmim][Al2Cl7] (Entries 7 and 8, Table 3).
With advantages of [Bmim][Al2Cl7] on enhanced reactivity and mildness, the reusability of
[Bmim][Al2Cl7] was focused on for examination. The [Bmim][Al2Cl7] collected after separation
from the previ◦ous reactions was washed with diethyl ether, subsequently evaporated under reduced
pressure at 80 C for 30 min and obtained in 82% of recycled yield. The structure of recovered catalyst
at the fourth recycle time was comparable with that of the fresh [Bmim][Al2Cl7] by 1H-NMR spectra.
The recycled [Bmim][Al2Cl7] was used for the sulfinylation of 1,3-dimethoxybezene with methyl
benzenesulfinate as that of the optimized experiment presented in Entry 1, Table 2. The catalytic
efficiency of [Bmim][Al2Cl7] did not drop significantly even after three runs of being reused and
recycled (Figure 1).

Molecules 2017, 22, 1458
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80
60
40
20
0
73
69
67
59
1
2
3
4
Catalyst run
Figure 1. Reusability of [Bmim][Al2Cl7] (1.2 mmol) in the sulfinylation of 1,3-dimethoxybenzene
(1 mmol) with methyl benzenesulfinate (1 mmol) under one-hour of ultrasound irradiation.
3. Discussion
According to several previous investigations on the formation of arenesulfinyl chloride
intermediates occurred reversibly from the corresponding alkyl arenesulfinates in the presence of
hydrogen chloride and chloride ions [41], arenesulfinyl chlorides (A) are obviously generated and
preserved under chloroaluminate-based 1-butyl-3-methylimidazole chloride (N = 0.67) owing to a large
number of chloride ions. Subsequently, the formation of sulfoxide can be explained by a mechanism
similar to that of the Friedel-Crafts sulfonylation of arenes [42], and the sulfenylation of indole [43].
It meant that a complex (
then released sulfinyl cation (
After that, an intermediate ( ) could be produced by an eletrophilic sulfinylation of electron rich arenes
B) of arenesulfinyl chloride with AlCl3 in [Bmim][Al2Cl7] was formed and
C
) which was efficiently stabilized by delocalized electrons of benzene.
D
with sulfinyl cation. Finally, a loss of a proton from (D) produced the sulfoxide product (Scheme 2).
4. Materials and Methods
4.1. Instrumentation
Microwave irradiation was performed by means of a CEM Discover microwave oven produced
by CEM Corporation, Matthews, NC, USA. Ultrasound irradiation was performed by means of
a BRANSON 1510 ultrasonic bath, operating at 40 kHz with a power output of 70 W. GC/MS
analyses were performed on a Hewlett Packard 6890 GC series II, apparatus of MS 5975C with a
triple-axis detector equipped with a J and W DB-5MS capillary column (30 m, 0.25 mm i.d., 0.25 µm
film thickness) and a Hewlett Packard 7683B autosampler. LC/MS analyses were performed on a
micrOTOF-QII-ESI-Qq-TOF (Bruker Daltonics, Bremen, Germany) with UV/VIS and MS detector,
◦
the heated capillary of iron trap mass spectrometer was set to 350 C, reverse column ACE 3C18
(5
µ
m
×
4.6
×
150 mm) and ESI (electrospray ionization): µQTOF Bruker. NMR spectra were recorded
on a Brüker 500 NMR spectrometer at 500 MHz (1H) and 125 MHz (13C).
4.2. Chemicals
All commercially available chemicals used were from Aldrich and analyzed for authenticity and
purity by GC/MS before being used.
Preparation of commercially unavailable alkyl alkanesulfinates/arenesulfinates: A solution of
N-bromosuccinimide (6 mmol, 1.067 g) dissolved in methanol (5 mL) and ethyl acetate (1 mL) was
added dropwise into the 25 mL two-neck round-bottom flask already containing thiol (3 mmol) in
methanol (5 mL), and then 4 mL of methanol was poured additionally up to 14 mL total amount. The
flask was placed into an ultrasound bath where the mixture of reactants was exposed to ultrasound
irradiation for a specific period of time. Subsequently, the reaction mixture was extracted with
dichloromethane (4
×
15 mL). The combined extracts were neutralized with a saturated solution of

Molecules 2017, 22, 1458
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NaHCO3, washed with water until neutral, and then dried by anhydrous Na2SO4. After removal of
the solvent by rotary evaporation, the remaining crude product was analyzed by GC/MS and purified
by column chromatography using eluent as a mixture of n-hexane and dichloromethane (6:4 v/v). The
identity and purity of all sulfinic esters obtained were confirmed by 1H-NMR, 13C-NMR and GC/MS
to make sure purity >99% (according to analysis by GC/MS) [44].
Preparation of [Bmim]Cl 2AlCl3: An amount of 1-methylimidazole (10 mmol, 1.745 g) and n-butyl
·
chloride (11 mmol, 1.018 g) were sequentially added into a 25 mL round-bottom flask assembled with
◦
the condenser. The reaction mixture was stirred magnetically with 250 rpm speed at 60–65 C for
24 h. After cooling down to room temperature, the reaction mixture was washed with diethyl ether
(5
×
10 mL) until no trace of n-butyl chloride, as well as 1-methylimidazole in a solution of diethyl
ether were detected by thin layer chromatography (TLC) and gas chromatography (GC). The other
solution containing recyclable [Bmim]Cl was evaporated under reduced pressure at 80 ◦C for 30 min
to afford a light yellow liquid in high yield (88%). The identity and purity of [Bmim]Cl obtained
were analyzed by 1H-NMR, 13C-NMR and LC/MS spectroscopy. In continuation of the preparation
of [Bmim]Cl 2AlCl3, an amount of aluminum chloride (4 mmol, 0.534 g) was added slowly into a
·
10 mL round-bottom flask containing [Bmim]Cl (2 mmol, 0.349 g). After that, the reaction mixture
were stirred magnetically at room temperature for 12 h. The identity and purity of acidic catalyst,
1
[Bmim]Cl
δ
·
2AlCl3, were checked by 1H-NMR and integrated as follows: H-NMR (500 MHz, D2O):
(ppm) 8.65 (s, 1H), 7.43 (s,1H), 7.38 (s, 1H), 4.14 (t, J = 7.0 Hz, 2H), 3.84 (s, 3H), 1.77–1.82 (m, 2H),
1.23–1.30 (m, 2H), 0.87 (t, J = 7.5 Hz, 3H).
4.3. General Procedure for the Sulfinylation of Aromatic Compound with Sulfinic Ester under
Ultrasound Irradiation
An amount of sulfinic ester (1 mmol), [Bmim][Al2Cl7] (1.2 mmol, 0.530 g) and aromatic compound
(1 mmol) were sequentially added into a test-tube (d = 1.5 cm, h = 16 cm) sealed with its cap. The
flask was placed into an ultrasound bath where the mixture of reactants was exposed to ultrasound
irradiation for a specific period of time. Subsequently, the reaction mixture was extracted with ethyl
acetate (3
×
15 mL). The combined extracts were dried by anhydrous Na2SO4. After the removal of
the solvent by rotary evaporation, the residue was purified by column chromatography using eluent
as a mixture of n-hexane and ethyl acetate.
4.4. Spectroscopic Data
The identity and purity of all products reported were confirmed by 1H-NMR, 13C-NMR, and
LC/MS. The unknown NMR spectroscopic data are described below and well-known compounds
(
3g
2,4-Dimethoxy-1-(phenylsulfinyl)benzene (3a). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
(ppm) 7.73 (d, J = 8.5 Hz, 1H), 7.66 (dd, J = 2.0 Hz, J = 8.0 Hz, 2H), 7.38–7.41 (m, 3H), 6.62
(dd, J = 2.0 Hz, J = 8.5 Hz, 1H), 6.39 (d, J = 2.0 Hz, 1H), 3.80 (s, 3H), 3.77 (s, 3H). 13C-NMR (125 MHz,
[45], 3i [32], [32], and 3k [32]) have been found compatible with those reported in the literature.
3i0
δ
CDCl3):
δ (ppm) 163.53, 157.30, 146.01, 130.56, 128.87 (2C), 126.55, 125.04 (2C), 124.90, 105.70, 98.95,
55.69, 55.58. HRMS-ESI: m/z [M + H]+ calcd. for C14H14SO3, 263.0736; found, 263.0732.
2,4-Dimethoxy-1-(ethylsulfinyl)benzene (3b). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ
(ppm) 7.64 (d, J = 8.5 Hz, 1H), 6.67 (dd, J = 8.5 Hz, J = 2.5 Hz, 1H), 6.45 (d, J = 2.5 Hz, 1H), 3.84 (s, 3H),
3.83 (s, 3H), 2.97–3.05 (m, 1H), 2.73–2.81 (m, 1H), 1.18 (t, J = 7.5 Hz, 3H). 13C-NMR (125 MHz, CDCl3):
(ppm) 163.30, 156.36, 127.14, 121.74, 105.20, 98.77, 55.69, 55.61, 46.89, 5.64. HRMS-ESI: m/z [M + H]+
δ
calcd. for C10H14SO3, 215.0736; found, 215.0758.
2,4-Dimethoxy-1-(2-propylsulfinyl)benzene (3c). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ
(ppm) 7.62 (d, J = 8.5 Hz, 1H), 6.66 (dd, J = 8.5 Hz, J = 2.0 Hz, 1H), 6.45 (d, J = 2.0 Hz, 1H),
3.84 (s, 3H), 3.83 (s, 3H), 3.04–3.10 (m, 1H), 1.35 (d, J = 7.0 Hz, 3H), 1.03 (d, J = 6.5 Hz, 3H). 13C-NMR

Molecules 2017, 22, 1458
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(125 MHz, CDCl3):
δ
(ppm) 163.27, 156.80, 127.72, 120.72, 105.17, 98.61, 55.60, 55.51, 51.23, 16.82, 12.72.
HRMS-ESI: m/z [M + H]+ calcd. for C11H16SO3, 229.0893; found, 229.0907.
2,4-Dimethoxy-1-(octylsulfinyl)benzene (3d). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ
(ppm) 7.67 (d, J = 9.0 Hz, 1H), 6.67 (dd, J = 8.5 Hz, J = 2.0 Hz, 1H), 6.46 (d, J = 2.0 Hz, 1H),
3.84 (s, 6H), 2.94–2.98 (m, 1H), 2.75–2.78 (m, 1H), 1.79–1.82 (m, 1H), 1.58–1.61 (m, 1H), 1.24–1.29
(m, 10H), 0.86 (t, J = 7.0 Hz, 3H). 13C-NMR (125 MHz, CDCl3):
δ (ppm) 163.31, 156.36, 126.84, 122.46,
105.35, 98.81, 55.72, 55.63, 54.13, 31.75, 29.15, 29.03, 28.68, 22.59, 21.97, 14.04. HRMS-ESI: m/z [M + H]+
calcd. for C16H26SO3, 299.1675; found, 299.1675.
2,4-Dimethoxy-1-(p-tolylsulfinyl)benzene (3e). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ
(ppm) 7.73 (d, J = 8.5 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.63 (dd, J = 2.5 Hz,
J = 8.5 Hz, 1H), 6.39 (d, J = 2.5 Hz, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 2.34 (s, 3H). 13C-NMR (125 MHz,
CDCl3):
δ (ppm) 164.05, 157.82, 143.25, 141.64, 130.21 (2C), 127.06, 125.81 (2C), 125.48, 106.19, 99.54,
56.31, 56.20, 21.98. HRMS-ESI: m/z [M + H]+ calcd. for C15H16SO3, 277.0893; found, 277.0892.
2,4-Dimethoxy-1-((4-methoxyphenyl)sulfinyl)benzene (3f). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ
(ppm) 7.76 (d, J = 8.5 Hz, 1H), 7.58 (dd, J = 7.0 Hz, J = 2.0 Hz, 2H), 6.91 (dd, J =7.0 Hz, J = 2.0 Hz,
2H), 6.64 (dd, J = 8.5 Hz, J = 2.0 Hz, 1H), 6.39 (d, J = 2.0 Hz, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.74
(s, 3H). 13C-NMR (125 MHz, CDCl3):
δ (ppm) 163.37, 161.60, 157.05, 137.11, 127.21 (2C), 126.24, 124.96,
114.36 (2C), 105.44, 98.95, 55.69, 55.59, 55.42. HRMS-ESI: m/z [M+H]+ calcd. for C15H26SO4, 293.0842;
found, 293.0848.
1,2-Dimethoxy-4-(phenylsulfinyl)benzene (3h). Light brown liquid, 1H-NMR (500 MHz, CDCl3):
δ (ppm)
7.59 (dd, J = 1.5 Hz, J = 8.0 Hz, 2H), 7.41–7.45 (m, 3H), 7.19 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H), 7.13
(d, J = 2.0 Hz, 1H), 6.89 (d, J = 8.5 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H). 13C-NMR (125 MHz, CDCl3):
δ
(ppm) 151.79, 150.19, 145.97, 137.13, 130.88, 129.30 (2C), 124.70 (2C), 118.99, 111.21, 107.39, 56.22,
56.19. HRMS-ESI: m/z [M + H]+ calcd. for C14H14SO3, 263.0736; found, 263.0764.
◦
1
N,N-Dimethyl-4-(phenylsulfinyl)aniline (3j). White solid, m.p. 130–131 C [46], H-NMR (500 MHz,
DMSO): (ppm) 7.62 (dd, J = 1.5 Hz, J = 8.0 Hz, 2H), 7.42–7.50 (m, 5H), 6.70 (dd, J = 2.0 Hz, J = 7.0 Hz,
δ
2H), 3.01 (s, 6H). 13C-NMR (125 MHz, DMSO):
δ (ppm) 152.54, 146.38, 130.93, 130.30, 129.07 (2C), 127.83
(2C), 124.71 (2C), 112.08 (2C), 40.21 (2C). HRMS-ESI: m/z [M + H]+ calcd. for C14H15NSO, 246.0947;
found, 246.0946.
◦
1
2-Methoxy-1-(phenylsulfinyl)napthalene (3l). White solid, m.p. 100–101 C [47], H-NMR (500 MHz,
CDCl3): (ppm) 8.70 (dd, J = 8.5 Hz, J = 1.0 Hz, 1H), 7.96 (d, J = 9.5 Hz, 1H), 7.78 (dt, J = 8.0 Hz,
J = 1.0 Hz, 1H), 7.64 (dd, J = 1.0 Hz, J = 8.5 Hz, 2H), 7.45–7.49 (m, 1H), 7.35–7.42 (m, 4H), 7.28
(d, J = 9.0 Hz, 1H), 3.96 (s, 3H) [47]. 13C-NMR (125 MHz, CDCl3):
(ppm) 157.52, 145.26, 134.96,
δ
δ
131.99, 129.72, 129.64, 128.83 (2C), 128.79, 128.21, 124.65, 124.48 (2C), 123.74, 123.26, 113.32, 57.10. MS
(C17H14SO2): m/z = 282[M]+, 266, 234, 127, 77.
◦
1-Methyl-3-(phenylsulfinyl)indole (3m). White solid, m.p. 120–120.5 C [48], 1H-NMR (500 MHz, DMSO):
(ppm) 8.10 (s, 1H), 7.64 (dd, J = 1.5 Hz, J = 8.0 Hz, 2H), 7.50–7.54 (m, 3H), 7.46 (tt, J = 7.0 Hz, J = 1.0 Hz,
1H), 7.25 (dd, J = 8.0 Hz, J = 1.0 Hz, 1H), 7.22 (td, J = 8.0 Hz, J = 1.0 Hz, 1H), 7.01 (td, J = 8.0 Hz,
δ
J = 1.0 Hz, 1H), 3.85 (s, 3H) [48].13C-NMR (125 MHz, DMSO):
δ (ppm) 144.91, 137.56, 134.15, 129.99,
128.99 (2C), 124.39 (2C), 123.58, 122.85, 120.90, 119.05, 115.33, 111.14, 33.02. HRMS-ESI: m/z [M + H]+
calcd. for C15H13NSO, 256.0791; found, 256.0782.
3-(Phenylsulfinyl)indole (3n). White solid, m.p. 126–127 ◦C [48], 1H-NMR (500 MHz, DMSO):
δ (ppm)
11.93 (s, 1H), 8.11 (d, J = 3.0 Hz, 1H), 7.63–7.66 (m, 2H), 7.50–7.54 (m, 3H), 7.44–7.48 (m, 2H), 7.23
(d, J = 8.0 Hz, 1H), 7.15 (td, J = 8.0 Hz, J = 1.0 Hz, 1H), 6.94–6.97 (m, 1H) [47]. 13C-NMR (125 MHz,
DMSO):
δ (ppm) 144.98, 137.06, 130.81, 129.95, 128.99 (2C), 124.42 (2C), 123.18, 122.85, 120.66, 119.00,
116.33, 112.71. HRMS-ESI: m/z [M + H]+ calcd. for C14H11NSO, 242.0634; found, 242.0634.

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1
2-(Phenylsulfinyl)dibenzo[b,d]thiophene (3p). White solid, H-NMR (500 MHz, CDCl3):
δ
(ppm) 8.55
(d, J = 1.0 Hz, 1H), 8.22–8.24 (m, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.85–7.87 (m 1H), 7.71 (dd, J = 8.0 Hz,
J = 1.5 Hz, 2H), 7.59 (dd, J = 8.5 Hz, J = 1.5 Hz, 1H), 7.51–7.52 (m, 2H), 7.44–7.47 (m, 3H). 13C-NMR
(125 MHz, CDCl3) and HSQC:
δ (ppm) 145.77, 142.46, 141.88, 139.89, 136.21, 134.69, 131.17, 129.43
(2C), 127.63, 124.93 (3C), 123.75, 122.94, 122.66, 122.15, 118.19. HRMS-ESI: m/z [M + H]+ calcd. for
C18H12S2O, 309.0402; found: 309.0403.
2-(Phenylsulfinyl)-9H-fluorene (3q). White solid, 1H-NMR (500 MHz, CDCl3):
δ (ppm) 7.82–7.85 (m, 2H),
7.78 (d, J = 7.0 Hz, 1H), 7.67–7.70 (m, 2H), 7.65 (dd, J = 8.0 Hz, J = 2.0 Hz, 1H), 7.55 (d, J = 7.5 Hz, 1H),
7.41–7.49 (m, 3H), 7.38 (td, J = 7.5 Hz, J = 1.0 Hz, 1H), 7.35 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 3.91 (s, 1H).
13C-NMR (125 MHz, CDCl3):
δ (ppm) 146.03, 145.08, 144.50, 143.86, 143.71, 140.42, 131.06, 129.45 (2C),
128.03, 127.20, 125.34, 124.90 (2C), 124.26, 121.63, 120.67, 120.56, 37.06. HRMS-ESI: m/z [M + H]+ calcd.
for C19H14SO, 291.0838; found, 291.0839.
5. Conclusions
An efficient, highly regio-selective and green synthetic method to prepare sulfoxides has been
developed. Sulfinic esters appeared as greener, safer, and more stable electrophiles than sulfinyl
chlorides in order to improve the reaction process at room temperature instead of very low temperature.
[Bmim]Cl·2AlCl3 is found out to be a better acidic catalyst owing to its efficiency, easy operation and
recyclability. Moreover, ultrasound irradiation has good effects on the yields of sulfoxide products
within a shorter reaction time.
Supplementary Materials: Supplementary materials are available online. 1H-NMR and 13C-NMR of
unknown products.
Acknowledgments: The authors are grateful to the Vietnam National University of Ho Chi Minh City (VNU-HCM)
for financial support (Grant number C2015-18-12).
Author Contributions: T.X.T.L. conceived, designed the experiments and wrote the paper; N.-L.T.N. and H.-T.V.
performed the experiments and analyzed the data; and F.D. contributed reagents/materials/analysis tools and
wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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