Synthesis of thiol esters using nano CuO/Ionic liquid as an eco-friendly reductive system under microwave irradiation

Article abstract of DOI:10.1002/ejoc.201300295

We report an efficient, fast, and environmentally friendly method for the synthesis of a wide range of thiol esters using stable diorganoyl disulfides and acyl chlorides, using CuO nanoparticles and [pmim]Br as the reductive system. This method gave good to excellent isolated yields of the desired products after only three minutes of microwave irradiation. Furthermore, by using the same green approach, we were also able to synthesize thiocarbonates bearing interesting functionalities. We report an efficient, fast, and environmentally friendly method for the synthesis of thiol esters starting from diorganoyl disulfides and acyl chlorides, and using CuO nanoparticles and [pmim]Br as the reductive system. This approach gave good to excellent isolated yields of the desired products in only three minutes under microwave irradiation. Copyright

Full text of DOI:10.1002/ejoc.201300295

Job/Unit: O30295
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FULL PAPER
Organochalcogen Chemistry
J. B. Azeredo, M. Godoi, R. S. Schwab,
G. V. Botteselle, A. L. Braga* ........... 1–8
Synthesis of Thiol Esters Using Nano
CuO/Ionic Liquid as an Eco-Friendly Re-
ductive System Under Microwave Irradia-
tion
We report an efficient, fast, and environ-
mentally friendly method for the synthesis
of thiol esters starting from diorganoyl dis-
ulfides and acyl chlorides, and using CuO
nanoparticles and [pmim]Br as the re-
ductive system. This approach gave good
to excellent isolated yields of the desired
products in only three minutes under
microwave irradiation.
Keywords: Thiol esters / Ionic liquids /
Sulfur / Nanoparticles / Microwave chemis-
try / Copper
0000, 0–0
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A. L. Braga et al.
FULL PAPER
DOI: 10.1002/ejoc.201300295
Synthesis of Thiol Esters Using Nano CuO/Ionic Liquid as an Eco-Friendly
Reductive System Under Microwave Irradiation
Juliano B. Azeredo,[a] Marcelo Godoi,[a] Ricardo S. Schwab,[b] Giancarlo V. Botteselle,[a] and
Antonio L. Braga*[a]
Keywords: Thiol esters / Ionic liquids / Sulfur / Nanoparticles / Microwave chemistry / Copper
We report an efficient, fast, and environmentally friendly
method for the synthesis of a wide range of thiol esters using
stable diorganoyl disulfides and acyl chlorides, using CuO
nanoparticles and [pmim]Br as the reductive system. This
method gave good to excellent isolated yields of the desired
products after only three minutes of microwave irradiation.
Furthermore, by using the same green approach, we were
also able to synthesize thiocarbonates bearing interesting
functionalities.
Introduction
scribed in the literature.[15] For example, they have been pre-
pared from aldehydes using iBu2AlSR,[16] from anhydrides
using a base and thiol reagent combination,[17] and, more
recently, from carboxylic acids using DCC.[18] However, the
The scope and applications of organochalcogen chemis-
try have increased tremendously, especially in relation to
synthetic organic reactions, since sulfur-containing groups
have been used as important auxiliary functional groups in
several synthetic transformations.[1] Thiol esters are one of
the most useful and powerful building blocks in organic
chemistry. They have, for example, been used in C–C cross-
coupling reactions,[2] in the synthesis of carbonyl com-
pounds,[3] and in asymmetric transformations.[4] Further-
more, thiol esters have been used in native chemical ligation
for peptide-bond formation,[5] and in the synthesis of natu-
ral products.[6] These compounds also have biological rele-
vance, with applications in in-vivo tumor suppression[7] and
as anti-HIV agents.[8]
vast majority of reported methods have used acyl chlorides
[20]
with nucleophilic sulfur species[19] such as Hg(RS)2
or
RSSmI2.[21] Several other similar methods have been de-
scribed that involve the generation of thiolate anions by the
reductive cleavage of S–S bonds[22] or the deprotonation of
thiols.[23] The reductive coupling of disulfides and acyl
chlorides in an Rh/H2 system has also been reported.[24]
Nonetheless, it is well known that most of the reported pro-
tocols have their limitations, such as the use of toxic sol-
vents, long reaction times, harsh conditions, or the prob-
lems associated with the handling of some thiols.
On the other hand, ionic liquids (ILs) have been used in
recent years as an alternative reaction medium for a broad
range of chemical transformations.[25] These solvents have
certain features, such as nonvolatility, nonflammability,
thermal stability, and recyclability, that make them an at-
tractive medium for organic synthesis.[26] In this context,
ionic liquids have also been used as effective solvents for the
synthesis of thiol esters, either from thiols[27] or by reductive
cleavage of S–S bonds by metals[28] or PPh3.[29] We have
also used a bimetallic system of SnCl2/CuBr2 for the syn-
thesis of thiol esters,[30] using an excess of the bimetallic
reagent as the reducing agent. The development of new
catalytic methods for the preparation of thiol esters using
environmentally friendly reductive systems under mild reac-
tion conditions is highly desirable.
Nowadays, the most convenient methods to incorporate
a sulfur atom into an organic molecule generally involve the
in situ generation of a nucleophilic sulfur species. This avo-
ids the use of reagents with unpleasant odors such as thi-
ols.[9] Most of the methods described for the reduction of
S–S bonds use reagents such as hydroxide,[10] hydrazine,[11]
sodium hydrogen telluride,[12] [BnEt3N]2MoS4,[13] or ex-
pensive metals including indium salts.[14] The development
of new synthetic strategies to improve these transformations
is currently an area of great interest.
In this context, several methods for the synthesis of thiol
esters under different reaction conditions have been de-
[a] Departamento de Química, Universidade Federal de Santa
Catarina,
Florianópolis, SC 88040-970, Brazil
E-mail: braga.antonio@ufsc.br
Homepage: www.pgquimica.ufsc.br
The catalysis of organic transformations by metallic
nanostructures is currently an area of intensive research.[31]
Generally, nanoscale copper catalysts in combination with
ionic liquids provide more effective processes and allow
great advances in relation to traditional methods.[32] In this
context, CuO nanopowder, with its high surface area and
[b] Departamento de Química, Universidade Federal de São
Carlos,
São Carlos, SP 13565-905, Brazil
Homepage: www.ppgq.ufscar.br
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300295.
2
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Synthesis of Thiol Esters Using Nano CuO/Ionic Liquid
reactive morphology, has been studied as an effective cata- suggests that the counterion of the IL plays an important
lyst for a wide range of reactions.[33]
role in the reaction.
Flash-heating by microwave (MW) irradiation for the ac-
Once we had established the best ionic liquid, we evalu-
celeration of organic reactions is well established as a con- ated the amount of catalyst necessary to promote the reac-
venient method for accelerating reactions in the labora- tion efficiently (Table 2). Initially, the reaction was per-
tory.[34] From a “green” point of view, the use of this kind formed with 2.5 mol-% of catalyst, and the desired product
of irradiation under solvent-free conditions or using an was formed in only 68% yield (Table 2, entry 1). When the
ionic liquid as a solvent is emerging as an environmentally amount of nano CuO was increased to 5.0 mol-%, the yield
benign alternative in organic synthesis.[35]
also increased significantly (Table 2, entry 2). Similarly,
Bearing these factors in mind, and continuing our ongo- when 10 mol-% of nano CuO was used, the product was
ing research into organochalcogen chemistry,[36] in this pa- formed in 96% yield (Table 2, entry 3). Further increasing
per, we report a new method for the synthesis of thiol esters the amount of nano CuO to 20 mol-% did not affect the
using an environmentally friendly reductive system under yield (Table 2, entry 4). The catalytic activity of bulk CuO
microwave irradiation (Scheme 1). With this method, we was significantly lower than nano CuO, and it gave the de-
avoid the use of stoichiometric amounts of metals as well sired product in only 41% yield (Table 2, entry 5). To exam-
as strong reducing agents.
ine the difference between this method and our previously
reported method,[29] we tested CuBr2 as a catalyst for the
synthesis of thiol ester 3a. However, this copper salt was
not efficient as a catalyst for this transformation, and the
desired product was formed in only 30% yield (Table 2, en-
try 6).
Scheme 1. General synthesis of thiol esters.
Table 2. Optimization of the amount of copper catalyst.[a]
Results and Discussion
Initially, we focused our attention on the influence of dif-
ferent ionic liquids on the reaction (Table 1). To investigate
this, we chose p-methylbenzoyl chloride (1a) and diphenyl
disulfide (2a) as model substrates. We found that the nature
of the ionic liquid was important for the success of the reac-
tion. When [bmim]PF6 was used as the solvent, thiol ester
3a was obtained in only 45% yield (Table 1, entry 1). How-
ever, when [bmim]BF4 was used, thiol ester 3a was obtained
in 52% yield (Table 1, entry 2). When an ionic liquid with
a bromide counterion was used, a significant increase in the
yield was obtained (Table 1, entries 3 and 4). For instance,
the ionic liquid [bmim]Br gave the product in 87% yield
(Table 1, entry 3). When [pmim]Br was used, the yield of
the desired product was raised to 96% (Table 1, entry 4).
This result highlights the influence of the length of alkyl
chain of the imidazolium cation in this reaction, and also
Entry
Copper
source
Catalyst amount [mol-%] Yield [%][b]
1
2
3
4
5
6
CuOnano
CuOnano
CuOnano
CuOnano
CuO
2.5
5
68
81
96
96
41
30
10
20
10
10
CuBr2
[a] Reaction conditions: p-methylbenzoyl chloride (0.5 mmol), di-
phenyl disulfide (0.25 mmol), nano CuO, [pmim]Br (0.5 mL), MW
(100 W), 3 min. [b] Isolated yields.
We then studied the influence of the reaction time
(Table 3). Aiming to obtain an efficient method in terms of
energy economy, we turned our attention to establishing the
minimum reaction time associated with a good reaction
rate. When the reaction was performed for only 1 min, a
considerable decrease in the yield was observed (Table 3,
entry 3). However, when the reaction time was increased to
2 min, thiol ester 3a was obtained in 90% yield (Table 3,
entry 2). Thus, 3 min was selected as the optimum reaction
time.
Table 1. Optimization of the ionic liquid used for the synthesis of
thiol esters.[a]
Entry
Ionic Liquid
Yield [%][b]
Focusing on the influence of the microwave irradiation
on the reaction, we carried out the reaction at lower power
and also with conventional heating (Table 3, entries 4 and
5). When the power was decreased to 75 W, the yield de-
creased from 96 to 65% (Table 3, entry 4). When the reac-
tion was carried out with conventional heating, even after
24 h, only a 24% yield of the desired product was obtained
1
2
3
4
[bmim]PF6
[bmim]BF4
[bmim]Br
[pmim]Br
45
52
87
96
[a] Reaction conditions: p-methylbenzoyl chloride (0.5 mmol), di-
phenyl disulfide (0.25 mmol), nano CuO (10 mol-%), IL (0.5 mL),
MW (100 W), 180 °C, 3 min. [b] Isolated yields.
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Table 3. Optimization of the reaction conditions using p-meth- (Table 3, entry 5). To gain some insight into the mechanism,
ylbenzoyl chloride (1a) and diphenyl disulfide (2a).[a]
we evaluated the effect of a radical trap on the reaction
outcome. When TEMPO was used, for example, the desired
product was obtained in only 13% yield, which shows that
a radical process might be operating (Table 3, entry 6).
We explored the generality of our method by combining
other acyl chlorides 1b–f with diphenyl disulfide (2a)
(Table 4). With p-methylbenzoyl chloride, thiol ester 3a was
achieved in 96% yield (Table 4, entry 1). When a tert-butyl
group was attached at the para position of the aromatic
Entry
Power [W]
Time [min]
Yield [%][b]
1
2
3
100
100
100
75
–
100
3
2
1
3
1440
3
96
90
55
65
24
13
4
5[c]
6[d]
Table 5. Scope and generality in the synthesis of thiol esters 3i–q
using p-methylbenzoyl chloride (1a) and disulfides 2b–j.[a]
[a] Reaction conditions: p-methylbenzoyl chloride (0.5 mmol), di-
phenyl disulfide (0.25 mmol), nano CuO (10 mol-%), [pmim]Br
(0.5 mL), MW (100 W), 180 °C, time. [b] Isolated yields. [c] The re-
action was performed with conventional heating at 180 °C. [d] The
reaction was performed using TEMPO (0.5 mmol).
Table 4. Synthesis of thiol esters using different acyl chlorides.[a]
[a] Reaction conditions: acyl chloride (0.5 mmol), diphenyl disulf-
[a] Reaction conditions: p-methylbenzoyl chloride (0.5 mmol), dior-
ide (0.25 mmol), nano CuO (10 mol-%), MW (100 W), 180 °C, ganoyl disulfide (0.25 mmol), nano CuO (10 mol-%), MW (100 W),
3 min. [b] Isolated yields.
180 °C, 3 min. [b] Isolated yields.
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Synthesis of Thiol Esters Using Nano CuO/Ionic Liquid
ring, the corresponding product was obtained in moderate thiocarbonates containing interesting functional groups.
yield (Table 4, entry 2). When the aromatic ring had a When benzyl chloroformate (CbzCl; 1i) and 9-fluorenyl-
mildly or strongly electron-withdrawing substituent, the methyl chloroformate (FmocCl; 1j) were used as acylating
corresponding products were formed in lower yields agents, thiocarbonates 3r and 3s were obtained in 35 and
(Table 4, entries 3 and 4). With benzoyl chloride, the desired 50% yields, respectively (Figure 1).
product was formed in 76% yield (Table 4, entry 5). With a
In addition, we evaluated the possibility of recycling the
chloride substitutent at the ortho position, thiol ester 3f was nano CuO/ionic liquid system used in our reactions (Fig-
formed in moderate yield (Table 4, entry 4). We were also ure 2). After the reaction was complete, the nano CuO/IL
able to prepare thiol esters starting from aliphatic acyl system was recovered and reused for further reactions. The
chlorides. The yield decreased to 46% for the reaction of CuO/IL system was very effective, even after the fourth run,
acetyl chloride and diphenyl disulfide (Table 4, entry 7). giving thiol ester 3a in 86% yield. Thus, we have shown that
When pivaloyl chloride, a more hindered group, was used, this method is greener and more efficient than that de-
the desired product was formed in a lower yield (Table 4, scribed in our previous report,[30] in which it was possible
entry 8).
to recover and reuse only the ionic liquid. In this new proto-
We also investigated the reaction of p-methylbenzoyl col, it was possible to recycle and reuse, at the same time,
chloride with a wide range of structurally diverse dior- both the catalyst and the ionic liquid components of the
ganoyl disulfides under our reaction conditions (Table 5, nano CuO/IL system.
entries 1–10). When methoxy or methyl groups, both elec-
tron-donating groups, were attached at the para position
of the aromatic ring, the corresponding thiol esters were
obtained in 71 and 85% yields, respectively (Table 5, en-
tries 1 and 2). However, a disulfide with a nitro group at
the para position did not provide a very reactive nucleophile
under the same conditions, and thiol ester 3k was formed in
poor yield (Table 5, entry 3). With an electron-withdrawing
group at either the para or meta position, a slight decrease
in the yield was observed (Table 5, entries 4 and 5). On the
other hand, the disulfide with a methoxyphenyl substituent
at the ortho position on the aromatic ring provided the de-
sired product in moderate yield (Table 5, entry 6).
It is well known that aryl sulfides are more reactive than
alkyl ones and also much more easily cleaved.[37] Using the
same method, we also synthesized thiol esters starting from
aliphatic disulfides (Table 5, entries 7–9). When diethyl di-
sulfide was used as a nucleophile source, the desired prod-
Figure 2. Reuse of nano CuO/[pmim]Br system in the synthesis of
3a.
uct was formed in 88% yield (Table 5, entry 7). But when a
long-chain disulfide was used, the yield of the correspond-
ing product decreased dramatically (Table 5, entry 8). When
we used dibenzyl disulfide, thiol ester 3l was obtained in a
satisfactory yield (Table 5, entry 9).
Conclusions
Due to our success in the preparation of thiol esters, we
extended our method to the synthesis of thiocarbonates,
To summarize, we have described a new and rapid proto-
which can act as versatile protecting groups for sulfur func- col for the synthesis of thiol esters using an environmentally
tionalities.[38] Thus, we attempted to synthesize different friendly nano CuO/ionic liquid system under microwave ir-
Figure 1. Synthesis of thiocarbonates.
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129.2, 129.0, 126.3, 21.3 ppm. HRMS (ESI+): calcd. for C14H13OS
[M + H]+ 229.0682; found 229.0678.
radiation. In this way, we avoided the use of a base and
reducing agents. This new method allowed the preparation
of the desired products in good to excellent yields in very
short reaction times. The catalytic system was used for the
synthesis of thiol esters, and was easily recovered and re-
used for further reactions without loss of efficiency.
Furthermore, we extended our method to the synthesis of
thiocarbonates, which are also very important from a syn-
thetic point of view. This shows the broad scope of the
method. Studies to elucidate the mechanism of this reaction
are in progress in our laboratory.
S-Phenyl 4-tert-Butylbenzothioate (3b): Yield 0.083 g, 61%. 1H
NMR (400 MHz, CDCl3): δ = 7.93–8.12 (m, 5 H), 7.32–7.51 (m, 4
H), 1.35 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 165.5,
157.3, 130.2, 129.6, 126.4, 125.6, 125.4, 125.3, 36.2, 31.2 ppm.
HRMS (ESI+): calcd. for C17H19OS [M + H]+ 271.1151; found
271.1159.
1
S-Phenyl 4-Bromobenzothioate (3c): Yield 0.057 g, 39%. H NMR
(200 MHz, CDCl3): δ = 7.86 (d, J = 8.7 Hz, 2 H), 7.60 (d, J =
8.7 Hz, 2 H), 7.51–7.40 (m, 5 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 189.18, 135.50, 135.10, 132.13, 129.75, 129.31, 128.99,
128.81, 127.02 ppm. HRMS (ESI+): calcd. for C13H10BrOS [M +
H]+ 292.9630; found 292.9636.
Experimental Section
S-Phenyl 4-Nitrobenzothioate (3d): Yield 0.053 g, 41%. 1H NMR
(200 MHz, CDCl3): δ = 8.34 (d, J = 9.1 Hz, 2 H), 8.17 (d, J =
9.1 Hz, 2 H), 7.60–7.45 (m, 5 H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 188.90, 150.82, 141.46, 135.00, 130.17, 129.62, 128.60,
126.35, 124.11 ppm. HRMS (ESI+): calcd. for C13H10NO3S [M +
H]+ 260.0376; found 260.0381.
1
General Remarks: H (400 or 200 MHz) and 13C (100 or 50 MHz)
NMR spectra were recorded in CDCl3. Chemical shifts (δ) are re-
ported in ppm, and are calibrated to the TMS peak (1H) or to the
solvent peak (13C). ESI-Q-TOF MS measurements were performed
with a micrOTOF Q-II (Bruker Daltonics) mass spectrometer
equipped with an automatic syringe pump from KD Scientific for
sample injection. The ESI-Q-TOF mass spectrometer was running
at 4.5 kV at a desolvation temperature of 180 °C, and was operating
in the positive-ion mode. The standard electrospray (ESI) ion
source was used to generate the ions. Samples were injected in an
acetonitrile/methanol mixed solvent using a constant flow (3 μL/
min). The ESI-Q-TOF MS instrument was calibrated in the range
m/z = 50–3000 using an internal calibration standard (low-concen-
tration tuning mix solution) supplied by Agilent Technologies.
Data were processed using Bruker Data Analysis software version
4.0. Column chromatography was performed using Merck silica gel
(230–400 mesh). Thin-layer chromatography (TLC) was performed
using Merck silica gel GF254 plates (0.25 mm thickness). For visual-
ization, TLC plates were placed under ultraviolet light and then
stained using in acidic vanillin. The yields of the products given in
all tables are isolated yields. The ionic liquids were prepared ac-
cording to literature procedures.[39] All other solvents were used as
received unless otherwise noted. All reactions were performed in
10 mL sealed tubes in a commercially available monomode reactor
(CEM Discover) with IR monitoring and a non-invasive pressure
transducer.
S-Phenyl Benzothioate (3e): Yield 0.081 g, 76%. 1H NMR
(400 MHz, CDCl3): δ = 8.12–8.00 (m, 2 H), 7.60–7.20 (m, 3 H),
7.53–7.45 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 190.1,
136.6, 135.0, 133.7, 133.6, 130.1, 129.5, 128.7, 128.4, 127.5 ppm.
HRMS (ESI+): calcd. for C13H11OS [M + H]+ 215.0525; found
215.0523.
1
S-Phenyl 2-Chlorobenzothioate (3f): Yield 0,066 g, 53%. H NMR
(400 MHz, CDCl3): δ = 7.80–7.60 (m, 1 H), 7.71–7.23 (m, 8 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 189.8, 136.8, 134.4, 132.2,
130.7, 129.5, 129.1, 128.9, 127.2, 126.5 ppm. HRMS (ESI+): calcd.
for C13H10ClOS [M + H]+ 249.0135; found 249.0132.
S-Phenyl Ethanethioate (3g): Yield 0.034 g, 46%. 1H NMR
(400 MHz, CDCl3): δ = 7.4 (s, 5 H), 2.38 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 193.8, 134.3, 129.3, 129.0, 127.8, 30.0 ppm.
HRMS (ESI+): calcd. for C8H9OS [M + H]+ 153.0369; found
153.0374.
1
S-Phenyl 2,2-Dimethylpropanethioate (3h): Yield 0.038 g, 40%. H
NMR (400 MHz, CDCl3): δ = 7.3 (s, 5 H), 1.31 (s, 9 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 204.4, 134.9, 129.0, 128.9, 128.0,
46.8, 27.3 ppm. HRMS (ESI+): calcd. for C11H15OS [M + H]+
195.0838; found 195.0835.
General Procedure for the Synthesis of Thiol Esters Under Micro-
wave Irradiation: An oven-dried tube was allowed to cool to room
temperature under argon, and then acyl chloride (0.5 mmol), CuO
nanopowder (10 mol-%), diorganoyl disulfide (0.25 mmol), and
[pmim]Br (1 mL) were added. The tube was sealed and placed into
a CEM Discover microwave apparatus. Initially, a maximum irradi-
ation power of 100 W and a temperature of 180 °C were applied
for 3 min. When the reaction was complete, the product was ex-
tracted with diethyl ether. The solvent and volatiles were completely
removed under vacuum to give the crude product. The compounds
were purified by column chromatography over silica gel.
S-4-Methoxyphenyl 4-Methylbenzothioate (3i): Yield 0.091 g, 71%.
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.41
(d, J = 9.0 Hz, 2 H), 7.25 (d, J = 7.0 Hz, 2 H), 6.98 (d, J = 8.0 Hz,
2 H), 3.84 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 191.1, 161.2, 145.1, 138.9, 134.6, 129.8, 128.0, 118.6,
115.4, 55.8, 22.2 ppm. HRMS (ESI+): calcd. for C15H15O2S [M +
H]+ 259.0787; found 259.0784.
S-p-Toluyl 4-Methylbenzothioate (3j): Yield 0.103 g, 85%. 1H NMR
(400 MHz, CDCl3): δ = 7.91 (d, J = 8.1 Hz, 2 H), 7.38 (d, J =
8.1 Hz, 2 H), 7.26–7.23 (m, 4 H), 2.40 (s, 3 H), 2.38 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 190.5, 144.3, 139.6, 134.9, 134.1,
129.9, 129.3, 127.4, 123.9, 21.6, 21.3 ppm. HRMS (ESI+): calcd.
for C15H15OS [M + H]+ 243.0844; found 243.0838.
Recyclability Experiments: The nano CuO/[pmim]Br system was re-
cycled without loss of activity. After completion of the reaction
work-up, the catalyst/solvent mixture was washed with diethyl ether
(5ϫ 5 mL), and then dried under vacuum for reuse in subsequent
reactions.
S-(4-Nitrophenyl) 4-Methylbenzothioate (3k): Yield 0.023 g, 17%.
1H NMR (200 MHz, CDCl3): δ = 8.22 (d, J = 8.8 Hz, 2 H), 8.02
(d, J = 8.3 Hz, 2 H), 7.66 (d, J = 8.8 Hz, 2 H), 7.28 (d, J = 8.3 Hz,
2 H), 2.42 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 187.20,
148.01, 145.34, 136.38, 133.32, 130.48, 129.50, 127.59, 123.68,
1
S-Phenyl 4-Methylbenzothioate (3a): Yield 0.194 g, 96%. H NMR
(400 MHz, CDCl3): δ = 7.94 (d, J = 4.0 Hz, 2 H), 7.54–7.52 (m, 2
H), 7.47–7.45 (m, 3 H), 7.29 (d, J = 4.0 Hz, 2 H), 2.40 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 187.5, 143.8, 135.1, 132.0,
6
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Synthesis of Thiol Esters Using Nano CuO/Ionic Liquid
21.67 ppm. HRMS (ESI+): calcd. for C14H12NO3S [M + H]+
274.0532; found 274.0530.
senvolvimento Científico e Tecnológico (CNPq), INCT-Catálise,
and Fundação de Amparo à Pesquisa e Inovação do Estado de
Santa Catarina (FAPESC) for financial support. CAPES is also
acknowledged for the master fellowship received by J. B. A. We also
would like to thank Centro de Biologia Molecular e Estrutural
(CEBIME) for the HRMS analysis.
S-4-Chlorophenyl 4-Methylbenzothioate (3l): Yield 0.079 g, 61%. 1H
NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.1 Hz, 2 H), 7.425–
7.421 (m, 4 H), 7.27 (d, J = 8.1 Hz, 2 H), 2.42 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 189.1, 144.8, 136.3, 135.8, 133.8,
129.44, 129.41, 127.5, 126.0 21.7 ppm. HRMS (ESI+): calcd. for
C14H12ClOS [M + H]+ 263.0297; found 263.0298.
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S-3-Chlorophenyl 4-Methylbenzothioate (3m): Yield 0.062 g, 48%.
1H NMR (200 MHz, CDCl3): δ = 7.89 (d, J = 8.2 Hz, 2 H), 7.50–
7.34 (m, 4 H), 7.24 (d, J = 8.2 Hz, 2 H), 2.39 (s, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 188.70, 144.92, 134.79, 134.72,
133.85, 133.23, 130.15, 129.60, 129.54, 127.65, 21.75 ppm. HRMS
(ESI+): calcd. for C14H11ClOSNa [M + Na]+ 285.0111; found
285.0115.
S-2-Methoxyphenyl 4-Methylbenzothioate (3n): 0.053 g, 41%. 1H
NMR (200 MHz, CDCl3): δ = 7.70 (d, J = 8.3 Hz, 2 H), 7.24–7.14
(m, 2 H), 7.00 (d, J = 8.3 Hz, 2 H), 6.80–6.72 (m, 2 H), 3.58 (s, 3
H), 2.15 (s, 2 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 188.89,
159.85, 144.36, 137.37, 134.37, 131.73, 129.37, 121.21, 115.78,
111.73, 56.10, 21.73 ppm. HRMS (ESI+): calcd. for C15H15O2S [M
+ H]+ 259.0787; found 259.0790.
S-Ethyl 4-Methylbenzothioate (3o): Yield 0.079 g, 88%. 1H NMR
(200 MHz, CDCl3): δ = 7.86 (d, J = 8.0 Hz, 2 H), 7.23 (d, J =
8.0 Hz, 2 H), 3.06 (q, J = 7.3 Hz, 2 H), 2.39 (s, 3 H), 1.34 (t, J =
7.3 Hz, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 191.7, 144.0,
134.7, 129.2, 127.2, 23.3, 21.6, 14.8 ppm. HRMS (ESI+): calcd. for
C10H13OS [M + H]+ 181.0682; found 181.0682.
S-Dodecyl 4-Methylbenzothioate (3p): Yield 0.049 g, 31%. 1H
NMR (200 MHz, CDCl3): δ = 7.86 (d, J = 8.1 Hz, 2 H), 7.22 (d,
J = 8.1 Hz, 2 H), 3.05 (t, J = 7.6 Hz, 2 H), 2.39 (s, 3 H), 170–1.59
(m, 2 H), 1.25 (br. s, 18 H), 0.88 (t, J = 6.6 Hz, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 191.62, 143.88, 134.75, 129.13,
127.18, 31.89, 29.62, 29.60, 29.56, 29.48, 29.32, 29.14, 28.93, 28.92,
14.07 ppm. HRMS (ESI+): calcd. for C20H32SONa [M + Na]+
343.2073; found 343.2069.
1
S-Benzyl 4-Methylbenzothioate (3q): Yield 0.059 g, 49%. H NMR
(200 MHz, CDCl3): δ = 7.83 (d, J = 8.2 Hz, 2 H), 7.34–7.17 (m, 5
H), 7.12 (d, J = 8.2 Hz, 2 H), 4.25 (s, 2 H), 2.27 (s, 3 H) ppm. 13C
NMR (50 MHz, CDCl3): δ = 190.3, 143.9, 137.4, 134.0, 129.0,
128.9, 128.3, 127.0, 32.9, 21.4 ppm. HRMS (ESI+): calcd. for
C15H15OS [M + H]+ 243.0838; found 243.0839.
O-Benzyl S-Phenyl Carbonothioate (3r): Yield 0.042 g, 35%. 1H
NMR (200 MHz, CDCl3): δ = 7.49–7.47 (m, 3 H), 7.32–7.28 (m, 7
H), 5.17 (s, 2 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 169.3,
134.6, 129.3, 128.9, 128.3, 127.4, 69.0 ppm. HRMS (ESI+): calcd.
for C14H12O2SNa [M + Na]+ 267.0450; found 267.0445.
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1
0.083 g, 50%. H NMR (400 MHz, CDCl3): δ = 7.77–7.33 (m, 13
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Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data and copies of
1H and 13C NMR as well as mass spectra.
Acknowledgments
The authors are grateful to the Coordenação de Aperfeiçoamento
de Pessoal de Nível Superior (CAPES), Conselho Nacional de de-
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Eur. J. Org. Chem. 0000, 0–0
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www.eurjoc.org
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/KAP1
Date: 17-07-13 17:26:04
Pages: 8
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Received: February 27, 2013
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0