Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones under microwave irradiation using an environmentally benign KF/Al2O3/PEG-400 system

Article abstract of DOI:10.1007/s11164-015-2410-x

We describe a simple and rapid method for selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones promoted by KF/Al₂O₃ using PEG-400 as solvent under microwave irradiation. The protocol employs 3-O-tosyl glycerol 1,2-carbonate 1 and

Full text of DOI:10.1007/s11164-015-2410-x

Res Chem Intermed
DOI 10.1007/s11164-015-2410-x
Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones
under microwave irradiation using an environmentally
benign KF/Al2O3/PEG-400 system
Gelson Perin1 Cristian M. Silva1 Elton L. Borges1
•
•
•
Jose E. G. Duarte Helen A. Goulart1
Rafaela B. Silva1 Ricardo F. Schumacher1
1
•
•
´
•
Received: 22 October 2015 / Accepted: 23 December 2015
Ó Springer Science+Business Media Dordrecht 2016
Abstract We describe a simple and rapid method for selective synthesis of
4-thiomethyl-1,3-dioxolan-2-ones promoted by KF/Al2O3 using PEG-400 as solvent
under microwave irradiation. The protocol employs 3-O-tosyl glycerol 1,2-car-
bonate 1 and a diverse array of thiols 2 to afford corresponding 4-thiomethyl-1,3-
dioxolan-2-ones 3 in good yield and short reaction time compared with conventional
heating methods. Moreover, selective synthesis of 1,3-bis-arylthiopropan-2-ol 4 by
a stoichiometric and temperature-controlling reaction is presented.
Keywords Glycerol carbonate Á Thiol Á PEG-400 Á Microwave irradiation Á
KF/Al2O3
Introduction
Development of green methodologies from renewable resources has increased in
recent years, mainly due to the extensive use of solvents in industry and the
resulting impact on the environment, health, and safety [1]. Glycerol, an organic
waste product generated by the biodiesel industry, has recently been proposed as a
valuable green solvent [2]. The current availability of glycerol on a large scale, its
low cost, nontoxicity, nonflammability, biodegradability, in addition to its
production from renewable sources make it an ideal candidate for the development
of greener protocols [3, 4].
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2410-
x) contains supplementary material, which is available to authorized users.
&
Gelson Perin
gelson_perin@ufpel.edu.br
1
LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, Pelotas,
RS 96010-900, Brazil
123

G. Perin et al.
The search for chemicals obtained from renewable resources reflects the current
challenge facing chemists, and in this context, synthesis and use of glycerol 1,2-
carbonates (GC) is a good choice towards valorization of glycerol as a precursor of
new synthons in organic chemistry [5–10]. Special attention is warranted by 3-O-
tosyl glycerol 1,2-carbonate 1, which is considered a key derivative used as a
building block in organic synthesis for construction of new C–C, C–N, and C–O
bonds [11–13], including preparation of industrial value polymers [14, 15]. In this
context, synthesis [10, 16] and applications [17, 18] of 4-thiomethyl-1,3-dioxolan-2-
ones and their derivatives provide a research opportunity of industrial and
pharmaceutical interest towards use of new, high-value glycerol feedstock. Current
methods described in literature use toxic solvents or suffer from long reaction time,
problems with regioselectivity, or low reaction yield [10, 16]. In this regard,
development of practical, efficient, rapid, and selective methods to prepare this class
of compounds in an environmentally friendly manner is desirable.
Development of cleaner synthetic protocols, using alternative solvents such as
polyethylene glycol (PEG) [19] in organic synthesis, has increased in recent years.
PEG is nonvolatile, nontoxic, and recyclable and has shown promise as a solvent in
organic reactions such as Suzuki–Miyaura [20], Stille [21], and Heck cross-coupling
[22], Michael-type reaction [23], and Ullmann-type arylation of amines [24] and
thiols [25]. Furthermore, our research group recently described use of PEG as a
green solvent in simple cleavage of diorganyl dichalcogenides (S, Se, and Te) to
form chalcogen alkanes [26, 27] and alkenes [28].
In this context of greener systems, potassium fluoride supported on alumina (KF/
Al2O3), a heterogeneous solid base reviewed by Clark in 1980 [29], has also been
used as an alternative to conventional bases for a number of transformations. The
main advantage of its use is that most of the products can be isolated by simple
filtration, avoiding use of large amounts of aqueous solutions of inorganic salts and
organic solvent waste [30, 31]. In this sense, KF/Al2O3 has been satisfactorily
employed by our group in various organic transformations [32, 33], and more
recently, the KF/Al2O3/PEG-400 system was successfully used to prepare (Z)-
organylthioenynes [34], (Z)-1,2-bis-arylselanyl alkenes [35], and thioethers [36].
On the other hand, several researchers have also been looking for alternative
energy sources and in particular at use of microwave irradiation, which shows
important advantages compared with traditional methods, such as short reaction
time and high yield or selectivity in some cases [37–39]. Efficient use of microwave
irradiation associated with other principles of green chemistry has emerged as a
promising research field, and current findings have allowed application of this
Scheme 1 General scheme for synthesis of 4-thiomethyl-1,3-dioxolan-2-ones 3
123

Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones…
approach in synthetic procedures for preparation of organic and inorganic materials
[40–43].
In continuation of our interest in use of environmentally benign methodologies
and green reagents to prepare organochalcogen compounds, we describe herein a
selective and rapid method for synthesis of 4-thiomethyl-1,3-dioxolan-2-ones 3
promoted by KF/Al2O3 as heterogeneous base using PEG-400 as green solvent
under microwave irradiation (Scheme 1).
Results and discussion
Firstly, our efforts were focused on the development of an optimum set of reaction
conditions for synthesis of 4-phenylthiomethyl-1,3-dioxolan-2-one 3a, selecting
tosylated glycerol carbonate 1 and benzenethiol 2a as ideal starting materials
(Table 1).
Based on our recent findings related to synthesis of (Z)-thioenynes using KF/
Al2O3 [34], we began our studies by reacting tosylated glycerol carbonate 1
(0.5 mmol) with benzenethiol 2a (0.5 mmol) in presence of 0.12 g KF/Al2O3 (50 %
Table 1 Optimization of conditions for synthesis of 3a
Entry 2a (mmol) Al2O3/KF (w/w %) Solvent
Temperature (°C) Time (h) Yield (%)a
1
0.5
0.5
0.6
0.6
0.6
0.7
0.7
0.7
0.7
0.6
0.7
50
60
60
60
60
60
60
60
60
60
60
PEG-400 r.t.
PEG-400 r.t.
PEG-400 r.t.
PEG-400 r.t.
PEG-400 60
PEG-400 60
PEG-400 80
3.5
3.5
3.5
15
25
30
35
32
75
82
82b
80c
70d
72
82
2
3
4
5
2.5
2.5
2.5
2.5
2.5
0.25
0.25
6
7
8
THF
60
60
9
DMF
10
11
PEG-400 60e
PEG-400 60e
Reactions performed using 0.5 mmol 1, 0.12 g KF/Al2O3 (w/w %), and 3.0 mL solvent (PEG-400) under
nitrogen (N2) atmosphere
a
Yields are given for isolated products
b
Byproduct 1,3-bis-thiophenylpropan-2-ol 4a was isolated in 4 %
c
Byproduct 4a was isolated in 10 %
d
Byproduct 4a was isolated in 12 %
e
Reactions performed in a microwave reactor using irradiation power of 200 W
123

G. Perin et al.
w/w) using PEG-400 (3.0 mL) as solvent at room temperature for 3.5 h under N2
atmosphere (Table 1, entry 1). This first reaction was carried out using a
conventional magnetic stirrer, and under these reaction conditions, the product 3a
was obtained in only 25 % yield. With this first result in hand, we decided to slightly
increase the potassium fluoride concentration over the aluminum oxide to 60 %, and
in so doing, the product could be obtained in 30 % yield (Table 1, entry 2). When
the number of equivalents of the nucleophilic specie, thiol 2a, was increased from
0.5 to 0.6 mmol, higher conversion was observed, affording the desired product in
35 % yield (Table 1, entry 3). Longer reaction time (Table 1, entry 4) did not result
in increased yield of 3a; instead, at room temperature, diphenyl disulfide was
recovered in large quantities. Aiming to improve the reaction yield, temperature was
the parameter considered, and on increasing it to 60 °C the reaction proceeded
smoothly, furnishing the desired product 3a in satisfactory yield after 2.5 h
(Table 1, entry 5). When the same protocol was performed using 0.7 mmol thiol 2a,
the product 3a was obtained in 82 % yield, revealing the dependence of the reaction
yield on both a slight excess of the nucleophilic species and temperature (Table 1,
entry 6). Further increase in reaction temperature (80 °C) did not result in any
increase in reaction yield (Table 1, entry 7). To confirm the importance of PEG-400
to this reaction, two common laboratory solvents, tetrahydrofuran (THF) and N,N-
dimethylformamide (DMF), were also employed (Table 1, entries 8 and 9). Under
these reaction conditions, the expected products were furnished in 80 and 70 %
yield, respectively, but a loss in selectivity became strongly evident with the
formation of the disubstituted byproduct 4a in 10–12 % yield.
Use of microwave irradiation as an alternative heating method to conventional oil
baths increases the efficiency of heat transfer due to the focused irradiation,
providing shorter reaction time and higher conversion of starting materials [29, 30].
Thus, experiments using microwave irradiation at 60 °C were performed, and the
results are described in entries 10 and 11. On closer inspection of entry 11,
corresponding to reaction of tosylate glycerol carbonate 1 (0.5 mmol) with
benzenethiol 2a (0.7 mmol) under microwave irradiation (200 W) at 60 °C in
presence of KF/Al2O3 (60 %) using PEG-400 (3.0 mL) as solvent, one observes
isolation of the expected product 3a in 82 % yield after only 15 min.
With these best experimental conditions for synthesis of 3a in hand, we
envisaged extending this methodology to a variety of thiols 2b–j. Under the
optimized conditions (microwave irradiation at 60 °C in PEG-400), 4-thiomethyl-
1,3-dioxolan-2-ones 3b–j could be obtained efficiently in good yield. These results
are presented in Table 2.
When using aromatic thiols with electron-donating and electron-withdrawing
groups at para-position, the reaction was successfully performed with carbonate 1,
affording good yield of the respective 4-arylthio-1,2-glycerol carbonates 3b–
e (Table 2, entries 2–5). Moreover, when ortho-substituted thiols 2f and 2g were
used, the corresponding products were also satisfactorily obtained (Table 2,
entries 6 and 7). When the reaction was performed using 2-aminobenzenethiol
2h, lower yield was obtained with the desired product 3h isolated in 65 % (Table 2,
entry 8). This is unlikely to be due to steric effects because 3f and 3g were obtained
from 2f and 2g in high yield. Instead, this result may possibly be attributable to the
123

Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones…
Table 2 Scope of microwave-promoted synthesis of 4-thiomethyl-1,3-dioxolan-2-ones 3a–j using PEG-
400 as solventa
Entry
1
Thiol 2
2a
Product 3
Yield (%)b
82
3a
3b
3c
3d
3e
71
2
3
4
5
2b
80
85
71
2c
2d
2e
6
7
8
88
85
65
3f
3g
3h
2f
2g
2h
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G. Perin et al.
Table 2 continued
Entry
Thiol 2
Product 3
Yield (%)b
55
9
3i
2i
2j
10
40
3j
a
Reactions performed using 0.5 mmol 1, 0.7 mmol 2, 0.12 g KF/Al2O3 (60 %), and 3.0 mL solvent
(PEG-400) under nitrogen (N2) atmosphere using a microwave reactor (irradiation power of 200 W) at
60 °C for 15 min
b
Yields are given for isolated products
Table 3 Selectivity of KF/Al2O3-promoted synthesis of 1,3-bis-arylthiopropan-2-ols 4a–c
Entry
Method
Thiol 2
Product 4, Yield (%)c
Byproduct 3, Yield (%)c
1
2
Oil Batha
M.W.b
2a
2a
4a (97%)
4a (65%)
3a ( - )
3a (25%)
3
4
Oil Batha
M.W.b
2b
2b
4b (70%)
4b (85%)
3b (20%)
3b (5%)
5
6
Oil Batha
M.W.b
2e
2e
4c (88%)
4c (80%)
3e (3%)
3e (15%)
a
Reactions performed using 0.5 mmol 1, 1.4 mmol 2, 0.12 g KF/Al2O3 (60 %), and 3.0 mL solvent
(PEG-400) under nitrogen (N2) atmosphere using an oil bath at 90 °C for 15 h
b
Reactions performed using a microwave reactor (irradiation power of 200 W) at 90 °C for 3 h
Yields are given for isolated products
c
123

Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones…
high electron-donating ability of the amino group, therefore disfavoring proton
abstraction from the thiol. In addition to aromatic rings, the reaction was also
carried out with the heteroaromatic 2-mercaptobenzothiazole 2i to afford the desired
4-(benzo[d]thiazol-2-ylthio)methyl-1,3-dioxolan-2-one 3i in 55 % yield (Table 2,
entry 9). Finally, when the alkyl 1-dodecanethiol 2j was employed in presence of
3-O-tosyl glycerol 1,2-carbonate 1 and the KF/Al2O3/PEG-400 system, the dodecyl
sulfide 3j was synthesized in 40 % yield (Table 2, entry 10).
This simple and quick method enables selective and efficient synthesis of
4-thiomethyl-1,3-dioxolan-2-ones in good yield and short reaction time compared
with conventional heating.
It is important to mention that, when using these reaction conditions (KF/Al2O3
and PEG-400 at 60 °C, as described in Table 1, entries 6 and 11), side-products
formed by cleavage of the carbonate unit producing the corresponding diol or by
double incorporation of the thiol unit to generate the 1,3-bis-thiopropan-2-ol 4 (as
previously observed [10, 16]) were obtained in trace amounts. Moreover, these
findings prompted us to explore the possibility of developing a selective method for
synthesis of 1,3-bis-arylthiopropan-2-ol 4. In this regard, we carried out a reaction
employing 0.5 mmol of the carbonate 1 and 1.4 mmol of the benzenethiol 2a at
90 °C, which gave the corresponding disubstituted product in 97 % isolated yield
after 15 h using a conventional heating system (Table 3, entry 1). In contrast, when
employing microwave irradiation, no significant gain in the reaction was achieved
and the 1,3-bis-phenylthiopropan-2-ol 4a was obtained in 65 % after 3 h with 25 %
yield of 3a as byproduct (Table 3, entry 2). Moreover, when 1.4 equivalents of
thiols containing para-chloro 2b and para-methyl 2e groups were used under 90 °C,
the corresponding products were satisfactorily obtained under microwave irradiation
and oil bath conditions (Table 3, entries 3 and 6). Although a mixture of products
was observed, the desired bisulfide could be easily isolated by column
chromatography.
Conclusions
We describe herein use of focused microwave irradiation in a simple and selective
protocol for synthesis of 4-thiomethyl-1,3-dioxolan-2-ones 3a–j. The reactions were
performed under mild conditions, reacting the tosylated 1,2-glycerol carbonate 1
with a range of thiols 2 using Al2O3 supporting KF as heterogeneous base in PEG-
400 under microwave irradiation at 60 °C. The respective 4-thiomethyl-1,3-
dioxolan-2-ones 3 were obtained in good yield and short reaction time compared
with conventional heating methods. Moreover, an increase in thiol amount and
reaction temperature (90 °C) was selective to produce the bis-arylthiopropan-2-ol 4
in excellent yield using a conventional heating system.
123

G. Perin et al.
Experimental
Microwave reactions were conducted using a CEM Discover focused microwave
oven, operating at 2.45 GHz with a power of 200 W, in a glass vessel (10 mL)
sealed with Teflon cap, under magnetic stirring. Hydrogen nuclear magnetic
resonance (1H NMR) spectra were obtained using Bruker DPX 300 and DRX 500
(300–500 MHz) devices. Spectra were recorded in CDCl3 solution, and chemical
shifts are reported in parts per million, referenced to tetramethylsilane (TMS) as
external reference. Data are reported as follows: chemical shift (d), multiplicity,
coupling constant (J) in hertz, and integrated intensity. Carbon-13 nuclear magnetic
resonance (13C NMR) spectra were obtained at 75 MHz on a Bruker DPX-300
NMR and at 125 MHz on a Bruker DRX-500 spectrometer. Spectra were recorded
in CDCl3 solutions, and chemical shifts are reported in parts per million, referenced
to the solvent peak of CDCl3. Low-resolution mass spectra were obtained with a
Shimadzu GC–MS-QP2010 mass spectrometer. High-resolution mass spectra
(HRMS) were recorded on a Bruker Micro TOF-QII spectrometer 10,416. Column
chromatography was performed using Merck silica gel (230 and 400 mesh). Thin-
layer chromatography (TLC) was performed using Merck silica gel GF254,
0.25 mm thickness. For visualization, TLC plates were either placed under
ultraviolet light, or stained with iodine vapor or acidic vanillin.
General procedure for synthesis of 4-thiomethyl-1,3-dioxolan-2-ones 3a–j
(a) Conventional heating: In a 10-mL glass vial equipped with magnetic stirring
bar was added the tosylated glycerol carbonate 1 (0.5 mmol) and the
respective thiol 2 (0.7 mmol) in PEG-400 (3.0 mL) under nitrogen (N2)
atmosphere. KF/Al2O3 (60 %) was then added, and the mixture was heated at
60 °C for 2.5 h. After this time, ethyl acetate (20.0 mL) was added to the
crude reaction and the organic solution was separated from KF/Al2O3 by
filtration. The organic phase was washed with water (2 9 15.0 mL),
separated, and dried over MgSO4. The solvent was evaporated under reduced
pressure. The product was isolated by column chromatography using hexane
or hexane/ethyl acetate as eluent (9:1).
(b) Microwave heating: In a 10-mL glass vial equipped with small magnetic
stirring bar was added the tosylated glycerol carbonate 1 (0.5 mmol) and the
respective thiol 2 (0.7 mmol) in PEG-400 (3.0 mL) under nitrogen (N2)
atmosphere. KF/Al2O3 (60 %) was then added, and the mixture was irradiated
in a focused microwave reactor (CEM) at 60 °C (temperature measured with
an IR sensor on the outer surface of the reaction vial) for 15 min, using
irradiation power of 200 W and without pressure. The product was extracted
and purified as described for method (a). All the compounds 3a–j were
characterized, and the spectral data are listed below:
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Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones…
4-Phenylthiomethyl-1,3-dioxolan-2-one [10] (3a)
Yield: 0.086 g (82 %); yellow oil; 1H NMR (CDCl3, 300 MHz) d = 7.43–7.39 (m,
2H, Ar-H), 7.35–7.24 (m, 3H, Ar-H), 4.80–4.71 (m, 1H, O-CH), 4.51 (ddd, J = 8.8,
7.6, and 0.3 Hz, 1H, O-CH2), 4.24 (dd, J = 8.8 and 6.4 Hz, 1H, O-CH2), 3.36 (ddd,
J = 14.1, 4.5, and 0.3 Hz, 1H, S-CH2), 3.08 (dd, J = 14.1 and 8.3 Hz, 1H, S-CH2).
13C NMR (CDCl3, 75 MHz) d = 154.7, 133.4, 131.0, 129.6, 127.8, 74.6, 68.4, 36.9.
MS (EI): m/z (% relative intensity) = 210 (47.5), 123 (100.0), 77 (10.5), 45 (37.4).
4-(4-Chlorophenylthio)methyl-1,3-dioxolan-2-one (3b)
1
Yield: 0.087 g (71 %); white solid; m.p. 86–88 °C. H NMR (CDCl3, 500 MHz)
d = 7.36 (d, J = 8.7 Hz, 2H, Ar-H), 7.30 (d, J = 8.7 Hz, 2H, Ar-H), 4.80–4.75 (m,
1H, O-CH), 4.53 (dd, J = 8.8 and 8.0 Hz, 1H, O-CH2), 4.25 (dd, J = 8.8 and
6.3 Hz, 1H, O-CH2), 3.33 (dd, J = 14.2 and 4.5 Hz, 1H, S-CH2), 3.10 (dd, J = 14.2
and 7.9 Hz, 1H, S-CH2). 13C NMR (CDCl3, 125 MHz) d = 154.3, 133.9, 132.3,
131.8, 129.5, 74.5, 68.3, 37.3. MS (EI): m/z (% relative intensity) = 244 (51.7), 157
(100.0), 77 (4.3), 45 (51.7). HRMS: Calculated mass for C10H9ClO3S: [M ? H]?
245.0039, found: 245.0014.
4-(4-Bromophenylthio)methyl-1,3-dioxolan-2-one (3c)
1
Yield: 0.115 g (80 %); white solid; m.p. 87–89 °C. H NMR (CDCl3, 500 MHz)
d = 7.45 (d, J = 8.7 Hz, 2H, Ar-H), 7.28 (d, J = 8.7 Hz, 2H, Ar-H), 4.80–4.75 (m,
1H, O-CH), 4.53 (dd, J = 8.8 and 8.0 Hz, 1H, O-CH2), 4.25 (dd, J = 8.8 and
6.3 Hz, 1H, O-CH2), 3.34 (dd, J = 14.2 and 4.5 Hz, 1H, S-CH2), 3.10 (dd, J = 14.2
and 8.0 Hz, 1H, S-CH2). 13C NMR (CDCl3, 125 MHz) d = 154.2, 132.5, 132.4,
121.8, 74.5, 68.3, 37.1. MS (EI): m/z (% relative intensity) = 290 (M? ? 2, 47.9),
288 (44.3), 201 (80.0), 122 (100.0), 45 (19.4). HRMS: Calculated mass for
C10H9BrO3S: [M ? H]? 288.9534, found: 288.9518.
4-(4-Fluorophenylthio)methyl-1,3-dioxolan-2-one (3d)
1
Yield: 0.097 g (85 %); white solid; m.p. 44–45 °C. H NMR (CDCl3, 500 MHz)
d = 7.44 (dd, J = 8.6 and 5.2 Hz, 2H, Ar-H), 7.28 (t, J = 8.6 Hz, 2H, Ar-H),
4.79–4.73 (m, 1H, O-CH), 4.53 (dd, J = 8.8 and 8.0 Hz, 1H, O-CH2), 4.25 (dd,
J = 8.8 and 6.4 Hz, 1H, O-CH2), 3.29 (dd, J = 14.2 and 4.5 Hz, 1H, S-CH2), 3.07
(dd, J = 14.2 and 8.0 Hz, 1H, S-CH2). 13C NMR (CDCl3, 125 MHz) d = 162.1 (d,
J = 247.4), 154.3, 134.0 (d, J = 8.1), 128.2 (d, J = 3.5), 116.5 (d, J = 21.8), 74.6,
68.4, 38.2. MS (EI): m/z (% relative intensity) = 228 (61.4), 141 (100.0), 45 (41.2).
HRMS: Calculated mass for C10H9FO3S: [M ? H]? 229.0335, found: 229.0315.
4-(4-Tolylthio)methyl-1,3-dioxolan-2-one (3e)
1
Yield: 0.080 g (71 %); white solid; m.p. 53–55 °C. H NMR (CDCl3, 500 MHz)
d = 7.32 (d, J = 8.0 Hz, 2H, Ar-H), 7.14 (d, J = 8.0 Hz, 2H, Ar-H), 4.75–4.70 (m,
123

G. Perin et al.
1H, O-CH), 4.50 (dd, J = 8.8 and 8.0 Hz, 1H, O-CH2), 4.23 (dd, J = 8.8 and
6.4 Hz, 1H, O-CH2), 3.32 (dd, J = 14.1 and 4.4 Hz, 1H, S-CH2), 3.02 (dd, J = 14.1
and 8.7 Hz, 1H, S-CH2), 2.33 (s, 3H, Ar-CH3). 13C NMR (CDCl3, 125 MHz)
d = 154.4, 138.1, 131.7, 130.2, 129.3, 74.7, 68.5, 37.5, 21.0. MS (EI): m/z (%
relative intensity) = 224 (62.9), 137 (100.0), 122 (27.0), 45 (40.0). HRMS:
Calculated mass for C11H12O3S: [M ? H]? 225.0585, found: 225.0564.
4-(2-Chlorophenylthio)methyl-1,3-dioxolan-2-one (3f)
1
Yield: 0.107 g (88 %); white solid; m.p. 72–73 °C. H NMR (CDCl3, 500 MHz)
d = 7.48–7.46 (m, 1H, Ar-H), 7.44–7.42 (m, 1H, Ar-H), 7.28–7.23 (m, 2H, Ar-H),
4.80–4.75 (m, 1H, O-CH), 4.57 (dd, J = 8.9 and 8.0 Hz, 1H, O-CH2), 4.31 (dd,
J = 8.9 and 6.3 Hz, 1H, O-CH2), 3.40 (dd, J = 14.1 and 4.5 Hz, 1H, S-CH2), 3.13
(dd, J = 14.1 and 8.4 Hz, 1H, S-CH2). 13C NMR (CDCl3, 125 MHz) d = 154.3,
136.0, 132.1, 132.0, 130.3, 129.0, 127.6, 74.5, 68.5, 36.0. MS (EI): m/z (% relative
intensity) = 244 (50.5), 157 (100.0), 45 (46.2). HRMS: Calculated mass for
C10H9ClO3S: [M ? H]? 245.0039, found: 245.0019.
4-(2-Tolylthio)methyl-1,3-dioxolan-2-one (3g)
1
Yield: 0.095 g (85 %); white solid; m.p. 43–45 °C. H NMR (CDCl3, 500 MHz)
d = 7.38–7.35 (m, 1H, Ar-H), 7.24–7.17 (m, 3H, Ar-H), 4.77–4.72 (m, 1H, O-CH),
4.52 (dd, J = 8.8 and 7.9 Hz, 1H, O-CH2), 4.27 (dd, J = 8.8 and 6.3 Hz, 1H,
O-CH2), 3.35 (dd, J = 13.9 and 4.4 Hz, 1H, S-CH2), 3.03 (dd, J = 13.9 and 8.8 Hz,
1H, S-CH2), 2.42 (s, 1H, Ar-CH3). 13C NMR (CDCl3, 125 MHz) d = 154.4, 139.4,
132.2, 130.9, 130.8, 127.8, 126.9, 74.6, 68.6, 36.2, 20.5. MS (EI): m/z (% relative
intensity) = 224 (61.6), 137 (64.5), 122 (100.0), 45 (91.0). HRMS: Calculated mass
for C11H12O3S: [M ? H]? 225.0585, found: 225.0564.
4-(2-Aminophenylthio)methyl-1,3-dioxolan-2-one (3h)
Yield: 0.073 g (65 %); pale-yellow solid; m.p. 89–91 °C. 1H NMR (CDCl3,
300 MHz) d = 7.37 (dd, J = 7.4 and 1.5 Hz, 1H, Ar-H), 7.18 (ddd, J = 8.0, 7.4,
and 1.6 Hz, 1H, Ar-H), 6.71 (td, J = 7.4 and 1.3 Hz, 1H, Ar-H), 4.75–4.65 (m, 1H,
O-CH), 4.52 (dd, J = 8.7 and 8.0 Hz, 1H, O-CH2), 4.19 (dd, J = 8.7 and 6.4 Hz,
1H, O-CH2), 3.18 (dd, J = 13.8 and 4.8 Hz, 1H, S-CH2), 2.92 (dd, J = 13.8 and
8.3 Hz, 1H, S-CH2). 13C NMR (CDCl3, 75 MHz) d = 154.5, 148.6, 136.4, 131.0,
118.9, 115.4, 114.4, 75.2, 68.7, 36.5. MS (EI): m/z (% relative intensity) = 225
(61.5), 136 (48.0), 124 (100.0), 94 (33.3). HRMS: Calculated mass for C10H11-
NO3S: [M ? H]? 226.0538, found: 226.0523.
4-(Benzo[d]thiazol-2-ylthio)methyl-1,3-dioxolan-2-one (3i)
1
Yield: 0.073 g (55 %); yellow solid; m.p. 88–90 °C. H NMR (CDCl3, 300 MHz)
d = 7.88–7.84 (m, 1H, Ar-H), 7.79–7.76 (m, 1H, Ar-H), 7.47–7.44 (m, 1H, Ar-H),
7.36–7.31 (m, 1H, Ar-H), 5.26–5.17 (m, 1H, O-CH), 4.62 (dd, J = 9.0 and 8.1 Hz,
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Selective synthesis of 4-thiomethyl-1,3-dioxolan-2-ones…
1H, O-CH2), 4.42 (dd, J = 9.0 and 6.3 Hz, 1H, O-CH2), 3.91 (dd, J = 14.3 and
5.0 Hz, 1H, S-CH2), 3.63 (dd, J = 14.3 and 6.7 Hz, 1H, S-CH2). 13C NMR (CDCl3,
75 MHz) d = 164.2, 154.5, 152.5, 135.5, 126.3, 124.8, 121.6, 121.3, 74.8, 68.5,
34.8. MS (EI): m/z (% relative intensity) = 267 (19.9), 167 (100.0), 45 (50.6).
HRMS: Calculated mass for C11H9NO3S2: [M ? H]? 268.0102, found: 268.0090.
4-(Dodecylthio)methyl-1,3-dioxolan-2-one (3j)
1
Yield: 0.060 g (40 %); white solid; m.p. 54–56 °C. H NMR (CDCl3, 300 MHz)
d = 4.89–4.80 (m, 1H, O-CH), 4.57 (dd, J = 8.7 and 8.4 Hz, 1H, O-CH2), 4.29 (dd,
J = 8.7 and 6.5 Hz, 1H, O-CH2), 2.93 (dd, J = 14.1 and 4.5 Hz, 1H, S-CH2), 2.78
(dd, J = 14.1 and 7.7 Hz, 1H, S-CH2), 2.60 (t, J = 7.4 Hz, 2H, S-CH2CH2),
1.64–1.26 (m, 20H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (CDCl3, 75 MHz)
d = 154.6, 75.5, 68.6, 34.6, 33.0, 31.8, 29.6 (3C), 29.5, 29.4, 29.3, 29.1, 28.6, 22.6,
14.0. MS (EI): m/z (% relative intensity) = 302 (4.9), 215 (12.8), 201 (73.6), 73
(100.0). HRMS: Calculated mass for C16H30O3S: [M ? H]? 303.1994, found:
303.1992.
General procedure for synthesis of 1,3-bis-arylthiopropan-2-ol 4a–c
(a) Conventional heating: In a 10-mL glass vial equipped with magnetic stirring
bar was added the tosylated glycerol carbonate 1 (0.5 mmol) and the desired
thiol 2 (1.4 mmol) in PEG-400 (3.0 mL) under nitrogen (N2) atmosphere. KF/
Al2O3 (60 %) was then added, and the mixture was heated at 90 °C for 15 h.
After this time, ethyl acetate (20.0 mL) was added to the crude reaction and
the organic solution was separated from the KF/Al2O3 by filtration. The
organic phase was washed with water (2 9 15.0 mL), separated, and dried
over MgSO4. The solvent was evaporated under reduced pressure. The
product was isolated by column chromatography using hexane/ethyl acetate
as eluent (9:1).
(b) Microwave heating: In a 10-mL glass vial equipped with small magnetic
stirring bar was added the tosylated glycerol carbonate 1 (0.5 mmol) and the
desired thiol 2 (1.4 mmol) in PEG-400 (3.0 mL) under nitrogen (N2)
atmosphere. KF/Al2O3 (60 %) was then added, and the mixture was irradiated
in a focused microwave reactor (CEM) at 90 °C (temperature measured with
an IR sensor on the outer surface of the reaction vial) for 3 h, using irradiation
power of 200 W and without pressure. The product was extracted and purified
as described for method (a). The compound 4 was characterized, and the
spectral data are listed below:
1,3-bis-Phenylthiopropan-2-ol [10] (4a)
1H NMR (CDCl3, 300 MHz) d = 7.36–7.32 (m, 4H, Ar-H), 7.28–7.16 (m, 6H, Ar-
H), 3.82 (tt, J = 7.2 and 5.0 Hz, 1H, O-CH), 3.20 (dd, J = 13.8 and 5.0 Hz, 2H,
123

G. Perin et al.
S-CH2), 3.04 (dd, J = 13.8 and 7.2 Hz, 2H, S-CH2), 2.47 (brs, 1H). 13C NMR
(CDCl3, 75 MHz) d = 135.1, 129.9, 129.1, 126.7, 68.2, 40.0.
1,3-bis(4-Chlorophenylthio)propan-2-ol (4b)
1
White solid; m.p. 44–47 °C. H NMR (CDCl3, 300 MHz) d = 7.27–7.20 (m, 8H,
Ar-H), 3.81–3.73 (m, 1H, O-CH), 3.14 (dd, J = 13.7 and 5.0 Hz, 2H, S-CH2), 3.01
(dd, J = 13.7 and 7.2 Hz, 2H, S-CH2), 2.83 (brs, 1H, OH). 13C NMR (CDCl3,
75 MHz) d = 133.4, 132.8, 131.2, 129.2, 68.1, 40.2. MS (EI): m/z (% relative
intensity) = 344 (12.6), 158 (38.7), 143 (39.4), 77 (15.9), 45 (100.0). HRMS:
Calculated mass for C15H14Cl2OS2: [M ? Na]? 366.9761, found: 366.9778.
1,3-bis(4-Tolylthio)propan-2-ol (4c)
1
White solid; m.p. 44–46 °C. H NMR (CDCl3, 300 MHz) d = 7.27–7.22 (m, 4H,
Ar-H); 7.08–7.05 (m, 4H, Ar-H), 3.80–3.72 (m, 1H, O-CH), 3.13 (dd, J = 13.7 and
5.0 Hz, 2H, S-CH2), 2.98 (dd, J = 13.7 and 7.2 Hz, 2H, S-CH2), 2.80 (brs, 1H,
OH), 2.31 (s, 6H). 13C NMR (CDCl3, 75 MHz) d = 136.7, 131.2, 130.6, 129.7,
68.2, 40.6, 21.0. MS (EI): m/z (% relative intensity) = 304 (27.6), 138 (54.6), 123
(48.3), 91 (89.1), 77 (34.7), 45 (100.0). HRMS: Calculated mass for C17H20OS2:
[M ? Na]? 327.0853, found: 327.0859.
Acknowledgments The authors are grateful to CNPq, FAPERGS, CAPES, and FINEP for financial
support.
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