One-pot synthesis of thioesters with sodium thiosulfate as a sulfur surrogate under transition metal-free conditions

Article abstract of DOI:10.1039/c8ob00178b

In this paper, we report an efficient synthetic method for thioester formation from sodium thiosulfate pentahydrate, organic halides, and aryl anhydrides. In the one-pot two-step reactions developed in this study, sodium thiosulfate was used as the sulfur surrogate for acylation with anhydrides, followed by substitution with organic halides through the in situ generation of thioaroylate. Furthermore, two important organic compounds could be successfully synthesized using our developed method. The advantages of the one-pot two-step reactions are operational simplicity, structurally diverse products with 42%-90% yields, use of relatively low toxic and odourless reagents, and easy applicability to large-scale operation.

Full text of DOI:10.1039/c8ob00178b

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One-Pot Synthesis of Thioesters with Sodium Thiosulfate as
Sulfur Surrogate under Transition Metal-Free Conditions
YenꢀSen Liao,a and ChienꢀFu Liang*
Received 00th January 20xx,
Accepted 00th January 20xx
a
In this paper, we report an efficient synthetic method for thioester formation from sodium thiosulfate pentahydrate, organic
halides, and aryl anhydrides. In the oneꢀpot twoꢀstep reactions developed in this study, sodium thiosulfate was used as the
sulfur surrogate for acylation with anhydrides, followed by substitution with organic halides through the in situ generation
of thioaroylate. Furthermore, two important organic compounds could be successfully synthesized using our developed
method. The advantages of the oneꢀpot twoꢀstep reactions are operational simplicity, structurally diverse products with
42%–90% yields, use of relatively low toxic and odourless reagents, and easy applicability to largeꢀscale operation.
DOI: 10.1039/x0xx00000x
www.rsc.org/
(a) Previous work
Introduction
O
O
2-
Carbon–sulfur bond formation is valuable in organic
chemistry,1 and these bonds have received much attention due
to their wide application in natural products,2 materials,3 and
chemical biology.4 Hence, developing mild and new synthetic
methods for carbon–sulfur bond formation is still highly
desirable. Moreover, thioesters are one of the carbon–sulfur
bond derivatives and are useful and important building blocks
due to their acyl transfer ability in organic synthesis5 and
chemical biology.6 Conventional synthetic methods for
thioesters involve the substitution of thiol groups with acid
chloride or acid anhydride in the presence of strong bases, such
as triethylamine, pyridine, and 4ꢀdimethylaminopyridine,7 or
the condensation of thiol groups with carboxylic acid in the
presence of an activating agent, such as diethyl
phosphorochloridate or dicyclohexylcarbodiimide.8 More
recently, numerous synthetic methods have been developed for
MoS4
+
R'
OH
R
S
R'
R
OH
Cl
PPh3, NBS
O
O
S
S
R
X, K2CO3
+
Ar
H2N
NH2
Ar
S
R
surfactant
R2 X, NEt3
cat. DMAP
O
O
S
R2
R'
R'
+
R1
S
R1
OH
N
H
N
H
microwave, 160 o
C
O
O
[Pd]/Ligand
R
SO3Na
+ R'Si(OEt)3
R
CO Balloon
CuF2
R'
S
S
(b) Thiswork
O
O
(1) Na2S2O3 5H2O, DMF
2
R2
R1
(2)
R
X
R1
O
R1'
thioesters in organic synthesis, including the use of
acylbenzotriazoles as mild
Nꢀ
S
ꢀacylating agents;9 the substitution
R1 = Aryl; R2 = Aromatic, Aliphatic; One-pot, two steps;
40 examples
of alkyl halides with thiocarboxylic acid;10 metalꢀcatalyzed
thiocarbonylations with carbon monoxide;11 new activating
agents for condensation reactions of carboxylic acids with
Scheme 1. Synthetic methods for thioester formation
N
ꢀbromosuccinimide, ionic liquids, and phase transfer agent);12a
thiols,
such
as
azopyridines,
microwave/SiO2;15 and rongalite16]. Although thioesters can be
efficiently synthesized using numerous existing methods, one
disadvantage of most of the aforementioned methods is that the
thiol group has a foul smell. Moreover, the thiol group has a
propensity to undergo slow oxidation to form disulfide bonds.
Therefore, for thioester formation, new synthetic methods that
are more feasible and environmentally friendly are still in
strong demand. To solve the aforementioned problems, recent
studies have developed new sulfur surrogates, such as
tetrathiomolybdate17 and thiourea,18 through the in situ
generation of the sulfur atom during the reaction process
(Scheme 1a). Moreover, Jiang and coꢀworkers recently
chlorodiphenylphosphine/iodine/imidazole, and trifluoroacetic
acid;12 oxidative coupling of thioesterification between
aldehydes and thiols;13 thioester formation by the
functionalization of the C(sp3)ꢀH bond;14 and other synthetic
methods [(triflates, cesium fluoride, zeolites, zinc,
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exploited palladiumꢀcatalyzed the crossꢀcoupling reaction
involving organosilicon reagent and Bunte salt for thioester
formation (Scheme 1a).11d These sulfur surrogates are highly
desirable for developing new and interesting synthetic methods
for thioesters in chemistry. Hence, our research continuously
focuses on developing synthetic methods for carbon–sulfur
bond formation in which environmentally friendly agents are
used under transition metalꢀfree conditions. In this paper, we
report the successful preparation of thioesters in a oneꢀpot twoꢀ
step reaction under transition metalꢀfree conditions, in which
anhydrides were directly coupled with sodium thiosulfate
pentahydrate (Na2S2O3·5H2O), which was used as the sulfur
source (Scheme 1b).
Table 1. Optimization of the reaction conditions
Entrya
T (oC)
70
Solvent
Yield (%)b
73
1
2
DMF
ACN
MeOH
H2O
70
8
24
3
70
4
70
n.d.c
n.d.d
66e
5
70
H2O
6
70
DMF
DMF
DMF
DMF
DMF
DMF
DMF
7
70
61f
36
Results and Discussion
8
9
r.t.
50
47
The model study of the oneꢀpot twoꢀstep reaction of
10
11
12i
70
70
70
10g
thioester formation was optimized using benzoic anhydride
1
75h
and sodium thiosulfate pentahydrate with benzyl bromide
(Table 1). Initially, to investigate the reactivities of sodium
thiosulfate in different solvents, the reactions were performed
with dimethylformamide (DMF), acetonitrile (ACN), methanol
(MeOH), and water (H2O) under mild heating conditions (Table
1, entries 1–5). The results revealed that the reaction proceeded
more favorably with sodium thiosulfate in DMF than with
sodium thiosulfate in ACN, MeOH, or H2O. Therefore, DMF
was selected as the reaction solvent for further study. To
determine the accurate amount of sodium thiosulfate required,
the amount utilized was 1 equivalent (Table 1, entry 6) and 1.5
equivalent (Table 1, entry 7). When the amount of sodium
thiosulfate was increased, a reaction yield of only 61% was
found (Table 1, entry 7). Hence, entry 1 was found to be the
minimum amount of sodium thiosulfate required for optimum
activity. After optimizing the amount of sodium thiosulfate, the
reaction temperature was also optimized. The results revealed
that a low temperature resulted in a low reaction yield (Table 1,
entries 8–9). Unexpectedly, when anhydrous sodium thiosulfate
was utilized under the optimized condition, the desired product
1a was obtained in a reaction yield of only 10% (Table 1, entry
10). According to similar previous reports,19 we assumed that
n.d.j
a Reaction conditions: 1 equiv. anhydride, 1.1 equiv. Na2S2O3･5H2O, 1.5 equiv.
b
benzyl bromide, and DMF (0.067M) under nitrogen atmosphere. Isolated
yield. c Added 2wt % TXꢀ100 (PTC)/H2O to the reaction mixture, n.d. = not
d
e
detected. Added 2wt % SDS (PTC)/H2O to the reaction mixture. Use 1
f
g
equiv. Na2S2O3 ･5H2O. Use 1.5 equiv. Na2S2O3 ･5H2O. Use anhydrous
i
j
Na2S2O3. h Gram scale (1g of 1). Using benzoyl chloride. Got benzoic acid
and benzylthiol. PTC: Phase transfer catalyst.
Table 2. Thioesterification with various organic halides
O
O
O
(1) Na2S2O3 5H2O
DMF, 70 oC, 2 h
R
Ph
S
Ph
O
O
Ph
(2) RBr, 70 oC, t (h),
yield (%)a
1b-o
1
O
O
Ph
S
Ph
S
Ph
S
1b, 20 h/70%
1c, 5 h/74%
1d, 2 h/74%
O
O
Ph
S
Ph
S
1f, 3 h/70%
1e, 3 h/74%
hydrates in sodium thiosulfate can be recognized as
a
OMe
O
hydrogenꢀbonding donor and can be used as a general acid
catalyst for the activation of carbonyl groups. In addition, we
found that this optimized condition is suitable for largeꢀscale
procedures, which provided the desired product 1a in good
yields (Table 1, entry 11). The benzoyl chloride was applied to
optimized condition, and the result revealed that the desired
product was not obtained (Table 1, entry 12). The reaction of
aliphatic anhydrides including acetic, hexanoic and
phenylacetic anhydrides with sodium thiosulfate under
optimized conditions did not lead to the desired products.
To extend the scope of this study, the aforementioned
optimized conditions for the oneꢀpot twoꢀstep protocol were
employed to synthesize a series of functionalized thioesters by
using prepared aryl anhydrides, sodium thiosulfate
pentahydrate, and organic halides. Under these optimized
O
O
Ph
S
Ph
Cl
S
Ph
S
1g, 3 h/62%b
1h, 2 h/82%
1i, 2 h/75%
NO2
Br
O
O
O
OEt
OH
Ph
S
Ph
S
Ph
S
C12H25
O
1j, 2 h/82%
1k, 9 h/60%
1l, 4 h/61%
O
O
O
Ph
S
Ph
S
Ph
S
C(Ph)3
1o, 4 h/45%c,d
1n, 6 h/47%c
1m, 5 h/57%
Reaction conditions: 1 equiv. anhydride, 1.1 equiv. Na2S2O3･5H2O, 1.5 equiv. Rꢀ
Br, and DMF (0.067 M). a Oneꢀpot two steps yield. b Use 4ꢀchlorobenzyl chloride
c Use 3 equiv. organic halides.d Use trityl chloride.
2 | J. Name., 2012, 00, 1-3
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1o) within appropriate reaction times, with moderate to high
Table 3. Thioesterification with various aryl anhydrides.
isolated yields (45%–82%). Higher yields were obtained for
more reactive primary bromide compounds (1b
aryl benzylic bromide and allylꢀ and propargyl bromide, than
for those with a mediumꢀlength alkyl chain, such as ꢀbutyl
1k) and ꢀdodecyl bromide (1l). According to previous
–1j), such as
1. Na2S2O3 5H2O
DMF, 70 oC, t1
2. R2Br, 70 oC, t2
yielda
O
O
O
R2
R1
O
R1
R1
S
n
2a-10a, 2b-10b,
2c-2d, 3c-3e
(
n
2-10
study,18b,20 the reactivity of alkyl halides toward nucleophilic
addition is known to be reduced as the alkyl chain is
lengthened. Moreover, under our reaction conditions, the
reactions involving secondary and tertiary organic halides
provided favorable results, and the corresponding products 1n
and 1o were obtained in 47% and 45% isolated yields,
respectively. The steric hindrance from secondary and tertiary
alky halides hindered the substitution reaction. We also applied
these aforementioned optimized conditions to various prepared
anhydrides with benzylꢀ and allyl bromides (Table 3). A wide
range of aryl anhydrides21 were smoothly converted to
O
O
O
MeO
MeO
SAllyl
SBn
SBn
MeO
3a, 5 h/6 h/70%
2a, 5 h/6 h/68%
2b, 5 h/6 h/66%
Cl
Cl
O
O
O
SAllyl
SAllyl
SBn
MeO
3b, 5 h/6 h/67%
4a, 1 h/6 h/70%
4b, 1 h/6 h/72%
O
O
corresponding thioester adducts (2a
–10a, 2b–10b, 2c–2d, and
O
3c 3e), with moderate to high reaction yields (42%–90%). Aryl
–
SBn
SAllyl
SBn
anhydrides bearing electronꢀdonating groups (EDGs) and
electronꢀwithdrawing groups (EWGs) were successfully reacted
with sodium thiosulfate pentahydrate. Importantly, this aryl
system showed high functional group tolerance. Moreover,
F3C
Br
Br
5a, 1 h/4 h/71%
5b, 1 h/4 h/67%
6a, 1 h/6 h/73%
O
O
O
methoxyl (Table 3, entries 2a
entries 4a 4b), bromo (Table 3, entries 5a
(Table 3, entries 6a 6b), naphtha (Table 3, entries 7a
(Table 3, 9a 9b), and thiophene (Table 3, 10a 10b) products
–
2d and 3a
–
–
3b), chloro (Table 3,
5b), trifluoromethyl
7b), furan
SBn
SAllyl
SAllyl
–
ꢀ
ꢀ
F3C
6b, 1 h/5 h/42%
7a, 2 h/4 h/70%
7b, 2 h/3 h/66%
–
–
O
were all obtained in high yields under the reaction conditions.
In addition, the less reactive primary bromide compounds of 1ꢀ
bromobutane and 2ꢀbromoethanol were reacted with substituted
O
O
SAllyl
SBn
SBn
O
aryl anhydrides; this reaction provided favorable results (2c
–2d
8a, 2 h/5 h/73%b
8b, 2 h/6 h/71%b
9a, 1 h/3 h/90%
and 3c 3d). We found that when 2ꢀbromoethanol was replaced
–
O
O
O
with 2ꢀbromoethyl acetate, the reaction yield of thioester
formation increased to 56% (Table 3, 3e).
SAllyl
S
SBn
SAllyl
O
To further determine the applicability of this oneꢀpot twoꢀ
step reaction, we explored the possibility of performing this
reaction with unsymmetric aryl anhydrides.21 Hence, we
performed the reaction with benzyl bromide, sodium thiosulfate
pentahydrate, and three unsymmetric aryl anhydrides. The
results are summarized in Scheme 2. Benzoic 4ꢀ
S
9b, 1 h/4 h/68%
10a, 1 h/4 h/80%
10b, 1 h/3 h/70%
O
O
MeO
3
OH
S
MeO
S
methoxybenzoicꢀ (12) and benzoic 2ꢀchlorobenzoic (13
)
2d, 5 h/3 h/42%
2c, 5 h/6 h/61%
O
O
(a)
O
O
R
(1) Na2S2O3 5H2O
DMF, 70 oC, 2 h
S
S
3
Ph
O
+
+
1a
3a
(2) BnBr, 70 oC, 2 h
MeO
MeO
(40%)
(49%)
R = OH, 3d, 5 h/4 h/43%c
R = OAc, 3e, 5 h/3 h/56%c
OMe
3c, 5 h/6 h/67%
12
(b)
O
O
Cl
(1) Na2S2O3 5H2O
DMF, 70 oC, 1 h
1a
4a
Reaction conditions: 1 equiv. anhydride, 1.1 equiv. Na2S2O3･5H2O, 1.5 equiv.
Ph
O
a
b
c
R2Br,
Oneꢀpot two steps yield,
Use
3
equiv. R2Br.
Byproduct 4ꢀ
(31%)
(37%)
(2) BnBr, 70 oC, 1 h
methoxybenzoic dithioperoxyanhydride 11 was obtained with 23% and 36% in
3d and 3e conditions, respectively.
13
O
O
Cl
(c)
conditions, various structurally and electronically tuned organic
halides with benzoic anhydride were investigated (Table 2).
The results revealed that under the reaction conditions, different
(1) Na2S2O3 5H2O
DMF, 70 oC, 1 h
+
O
3a
4a
(24%) (46%)
(2) BnBr, 70 oC, 1 h
14
MeO
organic halides were easily converted to thioester adducts (1b
–
Scheme 2. Thioesterification with unsymmetric aryl anhydrides
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anhydrides were successfully utilized in this method (Scheme highly efficiently synthesized through acylation and
2a–2b). The results revealed that two thioester adducts were Sonogashira coupling.11d,23
obtained, and the reaction yields did not show a considerable
To understand the mechanism of this reaction, we
difference. Notably, when 2ꢀchlorobenzoic 4ꢀmethoxybenzoic conducted control experiments (Scheme 5). As shown in
anhydride (14) was used, the reaction yield of aryl thioester Scheme 5a, the reaction was first performed with sodium
bearing EWGs (4a, 46%) was higher than that of those bearing thiosulfate pentahydrate and benzyl bromide, and benzoic
EDGs (3a, 24%), as shown in Scheme 2c. We assumed that anhydride was then added. However, the result revealed that
EWGs on unsymmetric anhydride may induce
electronic effect, which resulted in high reactivity.
a
more multiple
spots
were
obtained
through
thinꢀlayer
chromatography. For comparison with the result in Scheme 5a,
Finally, to further demonstrate the synthetic utility of our
developed method in comparison with that of other reported
protocols, using the sequential oneꢀpot twoꢀstep strategy,
O
(1) BnBr, DMF
70 oC, 2 h
SBn
(a)
(b)
Na2S2O3 5H2O
benzoic anhydride
1 was transformed into the fungicide of
(2) Bz2O, 70 o
6 h
C
1a
chloroethylbenzoyl sulfide 1517 and the thiaꢀMichael adduct 16
Trace, including
multiple spots
(Scheme 3).22 The results revealed that the substitution addition
O
O
O
Na2S2O3 5H2O
SBn
Ph
O
Ph
BnBr, DMF
70 oC, 11 h
1a
25%
Scheme 5. Control experiments for the oneꢀpot thioester formation
sodium thiosulfate pentahydrate, benzyl bromide, and the
benzoic anhydride were stirred under the same reaction
conditions, which produced the desired product 1a in 25%
yield, as well as multiple spots, including those for the benzyl
disulfide byproduct, through thinꢀlayer chromatography
(Scheme 5b). Based on these results, we proposed a plausible
mechanism for this reaction (Scheme 6). An aryl anhydride
proceeds to undergo a nucleophilic acyl substitution reaction
with sodium thiosulfate to produce the corresponding Bunte salt
as an intermediate. After the addition of organic halide to the
reaction mixture, the salt spontaneously forms a thioaroylate
anion. Finally, the thioaroylate reacts with organic halide to
obtain the thioester product.
Scheme 3. Synthetic applications by oneꢀpot twoꢀstep method
product 15 was obtained in 66% yield from reaction with 1ꢀ
bromoꢀ2ꢀchloroethane. Moreover, this reaction did not produce
a
dimer byproduct, which had been formed through
intermolecular double substitution addition.17 In addition,
according to a previous study,22 the thiaꢀMichael addition
adduct 16 has been obtained in 52% yield through
intermolecular thiaꢀMichael addition with benzoic acid,
triphenylphosphine,
Nꢀbromosuccinimide, tetrathiomolybdate,
and cyclohexenone. By contrast, using our developed method,
the corresponding thioester was readily produced from the
benzoic anhydride through the in situ generation of
thioaroylate, which produced the desired product 16 with 61%
yield. Moreover, applications of thioesters for preparing
important organic compounds are illustrated with two efficient
transformations (Scheme 4). Amide 17 and alkynone 18 were
Scheme 6. A proposed mechanism for oneꢀpot twoꢀstep thioester formation
Conclusions
In this study, we presented an efficient, versatile, and odorless
method for the oneꢀpot synthesis of thioester compounds from
sodium thiosulfate pentahydrate, organic halides, and aryl
anhydrides under transition metalꢀfree conditions. In this
reaction, we demonstrated that sodium thiosulfate served as the
sulfur source for the formation of the Bunte salt with anhydride,
Scheme 4. Thioester transformations
4 | J. Name., 2012, 00, 1-3
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which was spontaneously formed through the in situ generation NMR (100 MHz, CDCl3): δ 191.3, 137.4, 136.8, 133.4, 129.0,
of thioaroylate for substitution with organic halides. 128.61, 128.59, 127.29, 127.26, 33.3.
Furthermore, we effectively synthesized two important organic
compounds by using our developed method and illustrated two S-allyl benzothioate (1b)13i
applications from the thioester product. Hence, we believe that Following general procedure, using benzoic anhydride (50.0
this oneꢀpot twoꢀstep synthetic method for thioester formation mg, 0.221 mmol), Na2S2O3ꢁ5H2O (60.3 mg, 0.243 mmol), and
can find wide application for the generation of organosulfur allyl bromide (40.1 mg, 0.332 mmol). The crude product was
compounds.
then purified by column chromatography (hexane/CH2Cl2, 8:1)
to afford 1b (27.7 mg, 70% yield) as a colorless oil; 1H NMR
(400 MHz, CDCl3): δ 7.97 (dd,
J = 8.5, 1.3 Hz, 2H), δ 7.58 (tt,
Experimental Section
J
= 7.4, 1.3 Hz, 1H), δ 7.48ꢀ7.43 (m, 2H), δ 5.95ꢀ5.85 (m, 1H),
δ 5.35ꢀ5.30 (m, 1H), δ 5.17ꢀ5.14 (m, 1H), δ 3.74 (dt, J = 6.9,
General Information
1.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 191.2, 136.9,
133.4, 133.0, 128.6, 127.2, 118.1, 31.8.
All reactions were performed under nitrogen atmosphere.
Solvents were purified following standard literature procedures.
1H NMR and 13C NMR spectra were reported on a Varian 400
MHz NMR spectrometer with CDCl3 as the solvent. Chemical
shifts were reported in parts per million (ppm) relative to
residual solvent peak (CDCl3 δ H = 7.26 ppm, δ C = 77.0 ppm).
The IR spectra were measured on a Thermo Scientific Nicolet
iS5 FTꢀIR spectrophotometer. TLC was performed on preꢀ
coated glass plates of Silica Gel 60 F254 (0.25 mm, E. Merck);
detection was performed by spraying with using a UV light and
a solution of phosphomolybdic acid (PMA) with heating. Flash
column chromatography was carried out on Silica Gel 60 (230–
400 mesh, E. Merck). High resolution mass spectrometry data
were recorded on ESI and EI source. Melting points were
measured by Thermo Scientific “MelꢀTemp” type melting point
apparatus and are uncorrected. The following abbreviations
were used to indicate multiplicities: s = singlet, d = doublet, t =
triplet, q = quartet, quin. = quintet, sex. = sextet, sep. = septet,
dd = doublet of doublets, dt = doublet of triplets, td = triplet of
doublets, tt = triplet of triplets, br = broad, m = multiplet.
S
-(prop-2-yn-1-yl) benzothioate (1c)18c
Following general procedure, using benzoic anhydride (100.0
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
propargyl bromide (78.88 mg, 0.663 mmol). The crude product
was then purified by column chromatography (hexane/CH2Cl2,
1
8:1) to afford 1c (57.3 mg, 74% yield) as a yellow oil; H NMR
(400 MHz, CDCl3): δ 7.96 (dd,
J
J
= 8.4, 1.2 Hz, 2H), δ 7.60 (tt,
= 7.5, 1.2 Hz, 1H), δ 7.49ꢀ7.45 (m, 2H), δ 3.84 (d, = 2.7 Hz,
= 2.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
J
2H), δ 2.22 (t,
J
189.9, 136.1, 133.7, 128.6, 127.2, 78.8, 71.0, 17.4.
S
-(4-methylbenzyl) benzothioate (1d)24
Following general procedure, using benzoic anhydride (100.0
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
4ꢀmethylbenzyl bromide (143.2 mg, 0.663 mmol). The crude
product was then purified by column chromatography
(hexane/CH2Cl2, 10:1) to afford 1d (79.1 mg, 74% yield) as a
colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.97 (d,
Hz, 2H), δ 7.56 (tt, = 7.5, 1.3 Hz, 1H), δ 7.46ꢀ7.42 (m, 2H), δ
7.28 (d, = 7.9 Hz, 2H), δ 7.13 (d, = 7.9 Hz, 2H), δ 4.30 (s,
J = 8.4
J
General procedure for synthesis of thioesters 1a-1o, 2a-10a, 2b-
10b, 2c-2d, 3c-3e
J
J
2H) δ 2.33 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 191.4,
137.0, 136.8, 134.3, 133.3, 129.3, 128.8, 128.5, 127.2, 33.1,
21.1.
To a solution of the organic anhydride (1.0 equiv.) in DMF (0.1
M) was added Na2S2O3ꢁ5H2O (1.1 equiv.) stirred at 70 oC under
nitrogen atmosphere for several hours, then the organic halide
(1.5 or 3.0 equiv.) in DMF was added to the reaction mixture
(overall, 0.067 M) and stirred at 70 oC under nitrogen
atmosphere. The resulting reaction mixture was stirred for
several hours until the reaction was completed as indicated by
TLC. The mixture was extracted with ether for three times and
the combined organic layer was washed with brine, dried over
MgSO4, filtered and concentrated. The crude products were
purified by flash column chromatography to afford the desired
product.
S
-(4-methoxybenzyl) benzothioate (1e)13i
Following general procedure, using benzoic anhydride (100.0
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
4ꢀmethoxybenzyl bromide (103.5 mg, 0.663 mmol). The crude
product was then purified by column chromatography
(hexane/CH2Cl2, 8:1) to afford 1e (83.9 mg, 74% yield) as a
colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.96 (d,
Hz, 2H), δ 7.56 (t, = 7.4 Hz, 1H), δ 7.44 (t, = 7.6 Hz, 2H), δ
7.30 (d, = 8.6 Hz, 2H), δ 6.85 (d, = 8.6 Hz, 2H), δ 4.28 (s,
J = 7.3
J
J
J
J
2H), δ 3.79 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 191.5,
158.8, 136.8, 133.3, 130.1, 129.4, 128.6, 127.2, 114.0, 55.2,
32.8.
S
-benzyl benzothioate (1a)13i
Following general procedure, using benzoic anhydride (50.0
mg, 0.221 mmol), Na2S2O3ꢁ5H2O (60.3 mg, 0.243 mmol), and
benzyl bromide (56.7 mg, 0.332 mmol). The crude product was
then purified by column chromatography (hexane/CH2Cl2, 8:1)
to afford 1a (36.8 mg, 73% yield) as a colorless oil; H NMR
(400 MHz, CDCl3): δ 7.97 (dd,
S
-(naphthalen-2-ylmethyl) benzothioate (1f)25
1
Following general procedure, using benzoic anhydride (100.0
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
2ꢀ(bromomethyl)naphthalene (146.6 mg, 0.663 mmol). The
crude product was then purified by column chromatography
J = 8.4, 1.2 Hz, 2H), δ 7.57 (tt,
J
= 7.5, 1.4 Hz, 1H), δ 7.47ꢀ7.42 (m, 2H), δ 7.39ꢀ7.37 (m, 2H),
δ 7.34ꢀ7.30 (m, 2H), δ 7.28ꢀ7.24 (m, 1H), δ 4.32 (s, 2H); 13C
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Journal Name
(hexane/CH2Cl2, 8:1) to afford 1f (86.3 mg, 70% yield) as a S-butyl benzothioate (1k)26
1
white solid; H NMR (400 MHz, CDCl3): δ 8.00ꢀ7.97 (m, 2H), Following general procedure, using benzoic anhydride (50.0
δ 7.85 (s, 1H), δ 7.82ꢀ7.80 (m, 3H), δ 7.57 (tt,
J = 7.4, 1.3 Hz, mg, 0.221 mmol), Na2S2O3ꢁ5H2O (60.3 mg, 0.243 mmol), and
1H), δ 7.50ꢀ7.43 (m, 5H), δ 4.49 (s, 2H); 13C NMR (100 MHz, 1ꢀbromobutane (45.4 mg, 0.332 mmol). The crude product was
CDCl3): δ 191.1, 136.7, 134.8, 133.4, 133.3, 132.5, 128.5, then purified by column chromatography (hexane/CH2Cl2, 8:1)
128.4, 127.7, 127.6, 127.2, 126.9, 126.2, 125.8, 33.5.
to afford 1k (25.6 mg, 60% yield) as a yellow oil; 1H NMR
(400 MHz, CDCl3): δ 7.97 (dd, = 8.4, 1.3 Hz, 2H), δ 7.60 (tt,
= 7.4, 1.3 Hz, 1H), δ 7.47ꢀ7.43 (m, 2H), δ 3.08 (t, = 7.3 Hz,
Following general procedure, using benzoic anhydride (100.0 2H), δ 1.70ꢀ1.62 (m, 2H), δ 1.50ꢀ1.41 (m, 2H), δ 0.95 (t, = 7.3
J
S
-(4-chlorobenzyl) benzothioate (1g)
J
J
J
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 192.1, 137.2, 133.1,
4ꢀchlorobenzyl chloride (106.8 mg, 0.663 mmol). The crude 128.5, 127.1, 31.6, 28.7, 22.0, 13.6.
product was then purified by column chromatography
(hexane/CH2Cl2, 8:1) to afford 1g (71.7 mg, 62% yield) as a
S
-dodecyl benzothioate (1l)13g
J = 8.4, Following general procedure, using benzoic anhydride (100.0
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.96 (dd,
1.3 Hz, 2H), δ 7.58 (tt,
J
= 7.4, 1.3 Hz, 1H), δ 7.47ꢀ7.43 (m, mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
2H), δ 7.34ꢀ7.27 (m, 4H), δ 4.27 (s, 2H); 13C NMR (100 MHz, 1ꢀbromododecane (165.3 mg, 0.663 mmol). The crude product
CDCl3): δ 190.9, 136.5, 136.1, 133.5, 133.1, 130.3, 128.7, was then purified by column chromatography (hexane/CH2Cl2,
128.6, 127.2, 32.5; IR (KBr):
912, 687 cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. for NMR (400 MHz, CDCl3): δ 7.99ꢀ7.96 (m, 2H), δ 7.56 (t,
C14H11ClNaOS: 285.0117, found: 285.0121. 7.4 Hz, 1H), δ 7.44 (t, = 7.7 Hz, 2H), δ 3.07 (t, = 7.3 Hz,
2H), δ 1.67 (quin., = 7.2 Hz, 2H), δ 1.46ꢀ1.39 (m, 2H), δ 1.32ꢀ
1.26 (m, 16H), δ 0.88 (t,
= 6.5 Hz, 3H); 13C NMR (100 MHz,
ν
= 3060, 2929, 1662, 1490, 1447, 30:1) to afford 1l (82.7 mg, 61% yield) as a colorless oil; 1H
J
=
J
J
J
S
-(4-nitrobenzyl) benzothioate (1h)18a
J
Following general procedure, using benzoic anhydride (100.0 CDCl3): δ 192.1, 137.3, 133.2, 128.5, 127.1, 31.9, 29.62
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and (CH2*2), 29.57, 29.55, 29.49, 29.3, 29.2, 29.1, 29.0, 22.7, 14.1.
4ꢀnitrobenzyl bromide (143.2 mg, 0.663 mmol). The crude
product was then purified by column chromatography (hexane/
S
-(2-hydroxyethyl) benzothioate (1m)27
EtOAc, 20:1) to afford 1h (99.5 mg, 82% yield) as a white Following general procedure, using benzoic anhydride (50.0
1
solid; m. p. 92ꢀ94 oC; H NMR (400 MHz, CDCl3): δ 8.19ꢀ8.16 mg, 0.221 mmol), Na2S2O3ꢁ5H2O (60.3 mg, 0.243 mmol), and
(m, 2H), δ 7.96 (dd, J = 8.4, 1.3 Hz, 2H), δ 7.62ꢀ7.54 (m, 3H), δ 2ꢀbromoethanol (41.4 mg, 0.332 mmol). The crude product was
7.49ꢀ7.44 (m, 2H), δ 4.37 (s, 2H); 13C NMR (100 MHz, then purified by column chromatography (hexane/EtOAc, 3:1)
1
CDCl3): δ 190.3, 147.0, 145.5, 136.2, 133.8, 129.7, 128.7, to afford 1m (22.9 mg, 57% yield) as a colorless oil; H NMR
127.3, 123.7, 32.4.
(400 MHz, CDCl3): δ 7.98 (dd,
= 7.4, 1.2 Hz, 1H), δ 7.48ꢀ7.44 (m, 2H), δ 3.87 (q,
2H), δ 3.30 (t, = 6.0 Hz, 2H), δ 2.03 (t,
= 4.5 Hz, 1H); 13C
J
= 8.4, 1.3 Hz, 2H), δ 7.59 (tt,
J
J
= 5.5 Hz,
S
-(4-bromobenzyl) benzothioate (1i)18a
J
J
Following general procedure, using benzoic anhydride (100.0 NMR (100 MHz, CDCl3): δ 192.2, 136.7, 133.5, 128.6, 127.2,
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and 61.7, 31.8.
4ꢀbromobenzyl bromide (165.7 mg, 0.663 mmol). The crude
product was then purified by column chromatography
(hexane/CH2Cl2, 8:1) to afford 1i (101.0 mg, 75% yield) as a Following general procedure, using benzoic anhydride (100.0
S
-isopropyl benzothioate (1n)28
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.95 (dd,
J = 8.4, mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
1.3 Hz, 2H), δ 7.58 (tt,
J = 7.4, 1.3 Hz, 1H), δ 7.47ꢀ7.42 (m, 2ꢀbromopropane (163.1 mg, 1.326 mmol). The crude product
4H), δ 7.27ꢀ7.25 (m, 2H), 4.26 (s, 2H); 13C NMR (100 MHz, was then purified by column chromatography (hexane/CH2Cl2,
1
CDCl3): δ 190.8, 136.6, 136.5, 133.5, 131.6, 130.6, 128.6, 8:1) to afford 1n (37.1 mg, 47% yield) as a colorless oil; H
127.2, 121.1, 32.5.
NMR (400 MHz, CDCl3): δ 7.94 (dd,
7.55 (tt, = 7.4, 1.2 Hz, 1H), δ 7.46ꢀ7.42 (m, 2H), δ 3.86 (sep.,
= 6.9 Hz, 1H), δ 1.41 (d,
= 6.9 Hz, 6H); 13C NMR (100
J = 8.3, 1.3 Hz, 2H), δ
J
Ethyl 2-(benzoylthio)acetate (1j)24
J
J
Following general procedure, using benzoic anhydride (100.0 MHz, CDCl3): δ 192.1, 137.3, 133.1, 128.5, 127.1, 34.9, 23.1.
mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
ethyl 2ꢀbromoacetate (110.7 mg, 0.663 mmol). The crude
S-trityl benzothioate (1o)
product was then purified by column chromatography (hexane/ Following general procedure, using benzoic anhydride (100.0
EtOAc, 8:1) to afford 1j (81.4 mg, 82% yield) as a colorless oil; mg, 0.442 mmol), Na2S2O3ꢁ5H2O (120.7 mg, 0.486 mmol), and
1H NMR (400 MHz, CDCl3): δ 7.98 (d,
J = 7.7 Hz, 2H), δ 7.60 trityl chloride (369.7 mg, 1.326 mmol). The crude product was
(t,
J = 7.6 Hz, 1H), δ 7.47 (t, J = 7.6 Hz, 2H), δ 4.23 (q, J = 7.1 then purified by column chromatography (hexane/CH2Cl2, 8:1)
Hz, 2H), δ 3.89 (s, 2H), δ 1.30 (t,
(100 MHz, CDCl3): δ 190.0, 168.7, 136.1, 133.7, 128.6, 127.3, oC; H NMR (400 MHz, CDCl3): δ 7.92 (d,
J
= 7.2 Hz, 3H); 13C NMR to afford 1o (75 mg, 45% yield) as a white solid; m. p. 178ꢀ180
1
J = 8.0 Hz, 2H), δ
61.8, 31.3, 14.0.
7.53 (t, J = 7.6 Hz, 1H), δ 7.39 (t, J = 7.6 Hz, 2H), δ 7.34ꢀ7.23
(m, 5H); 13C NMR (100 MHz, CDCl3): δ 189.7, 143.8, 137.4,
6 | J. Name., 2012, 00, 1-3
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ARTICLE
133.2, 129.9, 128.5, 127.8, 127.4, 127.1, 70.4; IR (KBr):
3052, 3029, 2923, 1667, 1483, 1441 cmꢀ1; HRMS (ESI) m/z: 1042 cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. for
[M+Na]+ calcd. for C26H20NaOS: 403.1127, found: 403.1118.
C10H12NaO3S: 235.0405, found: 235.0404.
ν
=
(KBr): ν = 3391, 3072, 2938, 2835, 1664, 1596, 1483, 1263,
S
-benzyl 3-methoxybenzothioate (2a)13e
S
-benzyl 4-methoxybenzothioate (3a)14a
Following general procedure, using 3ꢀmethoxybenzoic Following general procedure, using 4ꢀmethoxybenzoic
anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg, anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg,
0.192 mmol), and benzyl bromide (44.8 mg, 0.262 mmol). The 0.192 mmol), and benzyl bromide (44.8 mg, 0.262 mmol). The
crude product was then purified by column chromatography crude product was then purified by column chromatography
(hexane/EtOAc, 30:1) to afford 2a (30.9 mg, 68% yield) as a (hexane/EtOAc, 30:1) to afford 3a (31.7 mg, 70% yield) as a
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.59ꢀ7.56 (m, 1H), colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.95 (d,
δ 7.47 (t,
J
= 8.8
= 7.1 Hz, 2H), δ
= 8.8 Hz, 2H), δ 4.30 (s, 2H), δ
NMR (100 MHz, CDCl3): δ 191.2, 159.7, 138.1, 137.4, 129.6, 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 189.7, 163.8,
128.9, 128.6, 127.3, 119.93, 119.86, 111.4, 55.4, 33.4. 137.7, 129.6, 129.4, 128.9, 128.6, 127.2, 113.8, 55.5, 33.2.
J = 2.0 Hz, 1H), δ 7.39ꢀ7.30 (m, 5H), δ 7.27ꢀ7.24 (m, Hz, 2H), δ 7.37 (d, J = 7.3 Hz, 2H), δ 7.31 (t, J
1H), δ 7.12ꢀ7.10 (m, 1H), δ 4.32 (s, 2H), δ 3.85 (s, 3H); 13C 7.25ꢀ7.22 (m, 1H), δ 6.91 (d,
J
S
-allyl 3-methoxybenzothioate (2b)
S
-allyl 4-methoxybenzothioate (3b)29
Following general procedure, using 3ꢀmethoxybenzoic Following general procedure, using 4ꢀmethoxybenzoic
anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg, anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg,
0.192 mmol), and allyl bromide (31.7 mg, 0.262 mmol). The 0.192 mmol), and allyl bromide (31.7 mg, 0.262 mmol). The
crude product was then purified by column chromatography crude product was then purified by column chromatography
(hexane/CH2Cl2, 8:1) to afford 2b (23.8 mg, 66% yield) as a (hexane/CH2Cl2, 8:1) to afford 3b (24.3 mg, 67% yield) as a
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.59ꢀ7.56 (m, 1H), colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.95 (d,
J
= 8.8
= 8.8 Hz, 2H), δ 5.95ꢀ5.85 (m, 2H), δ 5.31
= 17.0 Hz, 1H), δ 5.14 (d, = 10.0 Hz, 1H), δ 3.87 (s, 3H),
δ 3.72 (d,
= 7.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
= 6.9 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 191.2, 159.7, 189.7, 163.7, 133.3, 129.8, 129.4, 117.8, 113.7, 55.5, 31.7.
138.2, 133.0, 129.6, 119.9, 118.1, 111.4, 55.4, 31.9; IR (KBr):
= 3081, 3005, 2937, 2835, 1663, 1596, 1484, 1427, 1262, 1041
cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. for C11H12NaO2S: Following general procedure, using 4ꢀmethoxybenzoic
δ 7.47 (t,
= 8.2, 2.4 Hz, 1H), δ 5.95ꢀ5.85 (m, 1H), δ 5.33 (d,
Hz, 1H), δ 5.16 (d, = 10.0 Hz, 1H), δ 3.85 (s, 3H), δ 3.73 (d,
J
= 2.2 Hz, 1H), δ 7.35 (t,
J
= 8.0 Hz, 1H), δ 7.12 (dd, Hz, 2H), δ 6.92 (d,
J
J
J
= 16.9 (d,
J
J
J
J
J
ν
S
-butyl 4-methoxybenzothioate (3c)13h
231.0456, found: 231.0448.
anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg,
0.192 mmol), and 1ꢀbromobutane (35.9 mg, 0.262 mmol). The
crude product was then purified by column chromatography
S
-butyl 3-methoxybenzothioate (2c)13e
Following general procedure, using 3ꢀmethoxybenzoic (hexane/EtOAc, 30:1) to afford 3c (26.4 mg, 67% yield) as a
anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg, colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.95 (d,
= 8.8
0.192 mmol), and 1ꢀbromobutane (35.9 mg, 0.262 mmol). The Hz, 2H), δ 6.92 (d, = 8.8 Hz, 2H), δ 3.86 (s, 3H), δ 3.05 (t,
crude product was then purified by column chromatography 7.3 Hz, 2H), δ 1.65 (quin., = 7.2 Hz, 2H), δ 1.45 (sex., = 7.4
(hexane/CH2Cl2, 8:1) to afford 2c (23.9 mg, 61% yield) as a Hz, 2H), δ 0.95 (t,
= 7.4 Hz, 3H); 13C NMR (100 MHz,
colorless oil; H NMR (400 MHz, CDCl3): δ 7.59ꢀ7.57 (m, 1H), CDCl3): δ 190.7, 163.6, 130.1, 129.3, 113.7, 55.5, 31.7, 28.6,
δ 7.47 (t, = 2.2 Hz, 1H), δ 7.35 (t, = 8.1 Hz, 1H), δ 7.11 (dd, 22.0, 13.6.
= 8.2, 2.6 Hz, 1H), δ 3.85 (s, 3H), δ 3.07 (t, = 7.4 Hz, 2H), δ
1.66 (quin., = 7.6 Hz, 2H), δ 1.46 (sex., = 7.4 Hz, 2H), δ
0.95 (t,
= 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 192.0, Following general procedure, using 4ꢀmethoxybenzoic
159.7, 138.6, 129.5, 119.8, 119.6, 111.4, 55.4, 31.6, 28.8, 22.0, anhydride (60.0 mg, 0.208 mmol), Na2S2O3ꢁ5H2O (57.3 mg,
J
J
J =
J
J
J
1
J
J
J
J
J
J
S
-(2-hydroxyethyl) 4-methoxybenzothioate (3d)30
J
13.6.
0.231 mmol), and 2ꢀbromoethanol (39.3 mg, 0.315 mmol). The
crude product was then purified by column chromatography
(hexane/EtOAc, 3:1) to afford 3d (19.2 mg, 43% yield) as a
S
-(2-hydroxyethyl) 3-methoxybenzothioate (2d)
Following general procedure, using 3ꢀmethoxybenzoic colorless oil; 1H NMR (400 MHz, CDCl3): δ 7.96 (d,
anhydride (50.0 mg, 0.175 mmol), Na2S2O3ꢁ5H2O (47.7 mg, Hz, 2H), δ 6.93 (d,
0.192 mmol), and 2ꢀbromoethanol (32.8 mg, 0.262 mmol). The (t,
= 6.0 Hz, 2H), δ 2.08 (br, 1H); 13C NMR (100 MHz,
J
= 9.0
J
= 9.0 Hz, 2H), δ 3.87ꢀ3.85 (m, 5H), δ 3.27
J
crude product was then purified by column chromatography CDCl3): δ 190.7, 163.9, 129.5, 113.7, 61.9, 55.5, 31.7.
(hexane/EtOAc, 3:1) to afford 2d (15.6 mg, 42% yield) as a
1
yellow oil; H NMR (400 MHz, CDCl3): δ 7.59 (d,
J
= 7.7 Hz, 2-((4-methoxybenzoyl)thio)ethyl acetate (3e)
= 8.0 Hz, 1H), δ Following general procedure, using 4ꢀmethoxybenzoic
= 6.0 Hz, anhydride (78.4 mg, 0.274 mmol), Na2S2O3ꢁ5H2O (74.8 mg,
1H), δ 7.47 (t,
7.14ꢀ7.11 (m, 1H), δ 3.88ꢀ3.86 (m, 5H), δ 3.29 (t,
2H), δ 1.97 (br, 1H); 13C NMR (100 MHz, CDCl3): δ 192.0, 0.301 mmol), and 2ꢀbromoethyl acetate (68.7 mg, 0.411 mmol).
159.6, 138.0, 129.6, 119.9, 119.9, 111.5, 61.7, 55.4, 31.8; IR The crude product was then purified by column
J = 2.4 Hz, 1H), δ 7.36 (t, J
J
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chromatography (hexane/EtOAc, 3:1) to afford 3e (39.1 mg, 128.6, 128.4, 118.3, 31.9; IR (KBr):
Journal Name
ν
= 3084, 3102, 2924,
56% yield) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ 1667, 1583, 1482, 1420, 640 cmꢀ1; HRMS (EI) m/z: [M]+ calcd.
7.95 (d,
= 6.5 Hz, 2H), δ 3.87 (s, 3H), δ 3.31 (t,
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 189.3, 170.7, 163.9,
129.52, 129.46, 113.8, 63.0, 55.5, 27.5, 20.8; IR (KBr):
J
= 9.0 Hz, 2H), δ 6.93 (d,
J
= 9.0 Hz, 2H), δ 4.26 (t,
J
for C10H9BrOS: 255.9557, found: 255.9550.
J
= 6.5 Hz, 2H), δ 2.07
S
-benzyl 4-(trifluoromethyl)benzothioate (6a)32
Following general procedure, using 4ꢀ(trifluoromethyl)benzoic
ν
=
30056, 2958, 2937, 2841, 1741, 1659, 1601, 1508, 1260, 1028 anhydride (58.0 mg, 0.160 mmol), Na2S2O3ꢁ5H2O (43.7 mg,
cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. for C10H12NaO3S: 0.176 mmol), and benzyl bromide (41.1 mg, 0.240 mmol). The
277.0511, found: 277.0502.
crude product was then purified by column chromatography
(hexane/CH2Cl2, 8:1) to afford 6a (34.4 mg, 73% yield) as a
white solid; m. p. 44ꢀ45 oC; 1H NMR (400 MHz, CDCl3): δ
S
-benzyl 2-chlorobenzothioate (4a)13c
Following general procedure, using 2ꢀchlorobenzoic anhydride 8.05 (d,
(90.0 mg, 0.306 mmol), Na2S2O3ꢁ5H2O (83.6 mg, 0.337 mmol), = 7.4 Hz, 2H), δ 7.32 (t,
and benzyl bromide (78.5 mg, 0.459 mmol). The crude product 4.34 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 190.4, 139.5,
was then purified by column chromatography (hexane/CH2Cl2, 136.9, 134.7 (q, = 33.0 Hz), 129.0, 128.7, 127.6, 127.5, 125.7
8:1) to afford 4a (55.8 mg, 70% yield) as a colorless oil; 1H (q,
= 3.5 Hz), 123.5 (q, = 271.0 Hz), 33.6.
NMR (400 MHz, CDCl3): δ 7.65 (dd, = 7.7, 1.4 Hz, 1H), δ
7.46ꢀ7.25 (m, 8H), δ 4.33 (s, 2H); 13C NMR (100 MHz,
CDCl3): δ 191.2, 137.1, 136.9, 132.2, 130.8, 129.2, 128.9, Following general procedure, using 4ꢀ(trifluoromethyl)benzoic
J
= 8.1 Hz, 2H), δ 7.70 (d ,
J = 8.2 Hz, 2H), δ 7.34 (d, J
J
= 7.3 Hz, 2H), δ 7.28ꢀ7.24 (m, 1H), δ
J
J
J
J
S
-allyl 4-(trifluoromethyl)benzothioate (6b)
128.7, 127.4, 126.6, 34.2.
anhydride (44.0 mg, 0.122 mmol), Na2S2O3ꢁ5H2O (33.2 mg,
0.134 mmol), and allyl bromide (22.1 mg, 0.183 mmol). The
crude product was then purified by column chromatography
S
-allyl 2-chlorobenzothioate (4b)
Following general procedure, using 2ꢀchlorobenzoic anhydride (hexane/CH2Cl2, 8:1) to afford 6b (12.6 mg, 42% yield) as a
(134.0 mg, 0.456 mmol), Na2S2O3ꢁ5H2O (124.4 mg, 0.501 colorless oil; 1H NMR (400 MHz, CDCl3): δ 8.06 (d,
= 8.1
mmol), and allyl bromide (82.7 mg, 0.684 mmol). The crude Hz, 2H), δ 7.72 (d, = 8.2 Hz, 2H), δ 5.95ꢀ5.85 (m, 1H), δ 5.35
product was then purified by column chromatography (dd, = 17.0, 1.3 Hz, 1H), δ 5.18 (dd, = 10.0, 1.1 Hz, 1H), δ
(hexane/CH2Cl2, 8:1) to afford 4b (69.9 mg, 72% yield) as a 3.76 (dt,
= 6.9, 1.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
J
J
J
J
J
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.66 (dd,
1.5 Hz, 1H), δ 7.46ꢀ7.39 (m, 2H), δ 7.32 (td, = 7.4, 1.5 Hz, 3.5 Hz), 123.5 (q,
1H), δ 5.96ꢀ5.86 (m, 1H), δ 5.34 (dd,
5.18 (d, = 10.0 Hz, 1H), δ 3.74 (d,
(100 MHz, CDCl3): δ 191.2, 137.3, 132.5, 132.2, 130.8, 129.2,
126.7, 118.5, 32.8; IR (KBr): = 3084, 3013, 2924, 1678, 1587,
1466, 1432, 912, 647 cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. Following general procedure, using 2ꢀnaphthoic anhydride
J
= 7.6, 190.4, 139.7, 134.7 (q,
J
= 28.0 Hz), 132.5, 127.6, 125.7 (q,
J
ν
=
=
J
J
= 272.0 Hz), 118.6, 32.1; IR (KBr):
J
= 16.9, 1.2 Hz, 1H), δ 3087, 2927, 1667, 1583, 1510, 1409, 1323 cmꢀ1; HRMS (EI)
J
J
= 7.0 Hz, 1H); 13C NMR m/z: [M]+ calcd. for C11H9F3OS: 246.0326, found: 246.0332.
ν
S
-benzyl naphthalene-2-carbothioate (7a)33
for C10H9ClNaOS: 234.9960, found: 234.9962.
(125.0 mg, 0.383 mmol), Na2S2O3ꢁ5H2O (104.7 mg, 0.422
mmol), and benzyl bromide (98.3 mg, 0.575 mmol). The crude
product was then purified by column chromatography
S
-benzyl 4-bromobenzothioate (5a)31
Following general procedure, using 4ꢀbromobenzoic anhydride (hexane/EtOAc, 30:1) to afford 7a (75.0 mg, 70% yield) as a
(81.9 mg, 0.214 mmol), Na2S2O3ꢁ5H2O (58.5 mg, 0.236 mmol), white solid; m. p. 73ꢀ74 oC; 1H NMR (400 MHz, CDCl3): δ
and benzyl bromide (55.0 mg, 0.322 mmol). The crude product 8.54 (s, 1H), δ 8.00 (dd,
was then purified by column chromatography (hexane/CH2Cl2, Hz, 1H), δ 7.90ꢀ7.86 (m, 2H), δ 7.62ꢀ7.53 (m, 2H), δ 7.42 (d,
8:1) to afford 5a (46.9 mg, 71% yield) as a white solid; m. p. = 7.2 Hz, 2H), δ 7.34 (t, = 7.4 Hz, 2H), δ 7.29ꢀ7.24 (m, 1H), δ
= 8.8 Hz, 4.38 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 191.1, 137.4,
J = 8.6, 1.8 Hz, 1H), δ 7.95 (d, J = 8.3
J
J
1
68ꢀ70 oC; H NMR (400 MHz, CDCl3): δ 7.83 (d,
J
2H), δ 7.59 (d,
J
= 8.8 Hz, 2H), δ 7.38ꢀ7.24 (m, 5H), δ 4.32 (s, 135.7, 134.0, 132.3, 129.4, 128.9, 128.64, 128.59, 128.4, 127.7,
2H); 13C NMR (100 MHz, CDCl3): δ 190.3, 137.1, 135.5, 127.3, 126.8, 123.1, 33.4.
131.9, 128.9, 128.7, 128.7, 128.5, 127.4, 33.5.
S
-allyl naphthalene-2-carbothioate (7b)34
S
-allyl 4-bromobenzothioate (5b)
Following general procedure, using 2ꢀnaphthoic anhydride
Following general procedure, using 4ꢀbromobenzoic anhydride (150.0 mg, 0.460 mmol), Na2S2O3ꢁ5H2O (125.6 mg, 0.506
(74.0 mg, 0.194 mmol), Na2S2O3ꢁ5H2O (52.9 mg, 0.213 mmol), mmol), and allyl bromide (83.5 mg, 0.690 mmol). The crude
and allyl bromide (35.2 mg, 0.291 mmol). The crude product product was then purified by column chromatography
was then purified by column chromatography (hexane/CH2Cl2, (hexane/CH2Cl2, 8:1) to afford 7b (69.1 mg, 66% yield) as a
1
10:1) to afford 5b (33.4 mg, 67% yield) as a colorless oil; 1H yellow oil; H NMR (400 MHz, CDCl3): δ 8.53 (s, 1H), δ 8.01ꢀ
NMR (400 MHz, CDCl3): δ 7.83 (d,
J
= 8.7 Hz, 2H), δ 7.59 (d, 7.96 (m, 2H), δ 7.90ꢀ7.86 (m, 2H), δ 7.62ꢀ7.54 (m, 2H), δ 6.00ꢀ
= 16.9, 1.4 5.90 (m, 1H), δ 5.37 (dd, = 16.9, 1.0 Hz, 1H), δ 5.18 (dd,
= 6.9, 1.2 Hz, 2H); 10.0, 1.0 Hz, 1H), δ 3.80 (dt,
= 6.9, 1.1 Hz, 2H); 13C NMR
J
= 8.6 Hz, 2H), δ 5.94ꢀ5.84 (m, 1H), δ 5.33 (dd,
J
J
J =
Hz, 1H), δ 5.18ꢀ5.14 (m, 1H), δ 3.73 (dt,
13C NMR (100 MHz, CDCl3): δ 190.2, 135.6, 132.7, 131.8,
J
J
8 | J. Name., 2012, 00, 1-3
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(100 MHz, CDCl3): δ 191.1, 135.7, 134.1, 133.1, 132.4, 129.5, Following general procedure, using thiopheneꢀ2ꢀcarboxylic
128.6, 128.4, 127.7, 126.8, 123.1, 118.1, 32.0.
-benzyl (E)-3-phenylprop-2-enethioate (8a)35
anhydride (125.0 mg, 0.525 mmol), Na2S2O3ꢁ5H2O (143.4 mg,
0.578 mmol), and benzyl bromide (134.8 mg, 0.788 mmol).
S
Following general procedure, using cinnamic anhydride (50.0 The crude product was then purified by column
mg, 0.180 mmol), Na2S2O3ꢁ5H2O (49.1 mg, 0.198 mmol), and chromatography (hexane/CH2Cl2, 8:1) to afford 10a (98.0 mg,
benzyl bromide (92.3 mg, 0.540 mmol). The crude product was 80% yield) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ
then purified by column chromatography (hexane/CH2Cl2, 8:1) 7.79 (dd,
J = 3.8, 1.1 Hz, 1H), δ 7.62 (dd, J = 4.9, 1.2 Hz, 1H),
to afford 8a (33.5 mg, 73% yield) as a white solid; m. p. 66ꢀ67 δ 7.38ꢀ7.36 (m, 2H), δ 7.34ꢀ7.30 (m, 2H), δ 7.27ꢀ7.24 (m, 1H),
1
oC; H NMR (400 MHz, CDCl3): δ 7.65(d,
J
= 15.8 Hz, 1H), δ δ 7.11 (dd,
MHz, CDCl3): δ 183.3, 141.7, 137.3, 132.7, 131.1, 128.9,
J
= 3.8, 4.9 Hz, 1H), δ 4.32 (s, 1H); 13C NMR (100
7.54 (dd, = 6.6, 3.1 Hz, 2H), δ 7.40ꢀ7.24 (m, 8H), δ 6.73 (d,
J
J
= 15.8 Hz, 1H), δ 4.28 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 128.6, 127.9, 127.4, 33.4.
189.1, 140.9, 137.6, 134.0, 130.6, 128.92, 128.87, 128.6, 128.4,
127.3, 124.6, 33.2.
S-allyl thiophene-2-carbothioate (10b)
Following general procedure, using thiopheneꢀ2ꢀcarboxylic
anhydride (150.0 mg, 0.630 mmol), Na2S2O3ꢁ5H2O (172.1 mg,
S
-allyl (E)-3-phenylprop-2-enethioate (8b)36
Following general procedure, using cinnamic anhydride (80.0 0.693 mmol), and allyl bromide (114.4 mg, 0.946 mmol). The
mg, 0.288 mmol), Na2S2O3ꢁ5H2O (78.5 mg, 0.316 mmol), and crude product was then purified by column chromatography
allyl bromide (104.4 mg, 0.863 mmol). The crude product was (hexane/CH2Cl2, 8:1) to afford 10b (81.2 mg, 70% yield) as a
1
then purified by column chromatography (hexane/CH2Cl2, 8:1) colorless oil; H NMR (400 MHz, CDCl3): δ 7.80 (dd,
J
= 3.8,
= 4.8
= 16.9, 1.2 Hz,
= 7.0 Hz, 2H); 13
= 16.9, 1.3 Hz, 1H), δ NMR (100 MHz, CDCl3): δ 183.2, 141.9, 132.9, 132.6, 131.1,
= 7.0 Hz, 2H); 13C NMR 127.8, 118.2, 32.0; IR (KBr):
= 3085, 3011, 2923, 1686, 1651,
(100 MHz, CDCl3): δ 189.0, 140.7, 134.0, 133.0, 130.5, 128.9, 1514, 1411, 1205 cmꢀ1; HRMS (ESI) m/z: [M+Na]+ calcd. for
to afford 8b (41.8 mg, 71% yield) as a yellow oil; 1H NMR 0.9 Hz, 1H), δ 7.62 (dd,
(400 MHz, CDCl3): δ 7.63 (d, = 15.8 Hz, 1H), δ 7.55 (dd, 4.0 Hz, 1H), δ 5.95ꢀ5.84 (m, 1H), δ 5.32 (dd,
6.7, 2.8 Hz, 2H), δ 7.41ꢀ7.38 (m, 3H), δ 6.72 (d, = 15.8 Hz, 1H), δ 5.15 (d, = 10.0 Hz, 1H), δ 3.73 (d,
1H), δ 5.92ꢀ5.82 (m, 1H), δ 5.30 (dd,
5.14 (d, = 10.0 Hz, 1H), δ 3.68 (d,
J = 4.9, 0.8 Hz, 1H), δ 7.11 (dd, J
J
J
=
J
J
J
J
C
J
J
J
ν
128.3, 124.7, 117.9, 31.7.
C8H8NaOS2: 206.9914, found: 206.9898.
S
-benzyl furan-2-carbothioate (9a)37
4-methoxybenzoic dithioperoxyanhydride (11)38
1
Following general procedure, using furanꢀ2ꢀcarboxylic White solid; m. p. 118ꢀ119 oC; H NMR (400 MHz, CDCl3): δ
anhydride (125.0 mg, 0.607 mmol), Na2S2O3ꢁ5H2O (165.6 mg, 8.06 (d,
J = 8.9 Hz, 4H), δ 6.98 (d, J = 8.9 Hz, 4H), δ 3.89 (s,
0.667 mmol), and benzyl bromide (155.7 mg, 0.910 mmol). 6H); 13C NMR (100 MHz, CDCl3): δ 184.7, 164.5, 130.5,
The crude product was then purified by column 128.0, 114.1, 55.6.
chromatography (hexane/CH2Cl2, 8:1) to afford 9a (119 mg,
90% yield) as a colorless oil; 1H NMR (400 MHz, CDCl3): δ
7.57 (dd, = 1.5, 0.6 Hz, 1H), δ 7.36 (d,
(t, = 7.4 Hz, 2H), δ 7.27ꢀ7.23 (m, 1H), δ 7.20 (dd,
Hz, 1H), δ 6.53 (dd,
= 3.6, 1.7 Hz, 1H), δ 4.30 (s, 2H); 13C mg, 0.486 mmol, 1.1 equiv.) stirred at 70 C under nitrogen
NMR (100 MHz, CDCl3): δ 179.8, 150.5, 146.1, 137.2, 128.9, atmosphere for 2 hours, then the 1ꢀbromoꢀ2ꢀchloroethane
S
-(2-chloroethyl) benzothioate (15)17
= 7.7 Hz, 2H), δ 7.31 To a solution of the benzoic anhydride (100.0 mg, 0.442 mmol,
= 3.5, 0.6 1.0 equiv.) in DMF (0.1 M) was added Na2S2O3ꢁ5H2O (120.7
J
J
J
J
o
J
128.6, 127.3, 115.7, 112.2, 32.3.
(627.3 mg, 4.420 mmol, 10 equiv.) in DMF was added to the
reaction mixture (overall, 0.067 M) and stirred at 70 C under
o
S
-allyl furan-2-carbothioate (9b)
nitrogen atmosphere. The resulting reaction mixture was stirred
Following general procedure, using furanꢀ2ꢀcarboxylic for 3 hours until the reaction was complete as indicated by
anhydride (50.1 mg, 0.243 mmol), Na2S2O3ꢁ5H2O (66.4 mg, TLC. After the reaction was completed, the mixture was
0.268 mmol), and allyl bromide (44.1 mg, 0.364 mmol). The extracted with ether for three times and the combined organic
crude product was then purified by column chromatography layer was washed with brine, dried over MgSO4, filtered and
(hexane/CH2Cl2, 8:1) to afford 9b (27.9 mg, 68% yield) as a concentrated. The crude product was then purified by column
1
colorless oil; H NMR (400 MHz, CDCl3): δ 7.58 (dd,
J = 1.6, chromatography (hexane/CH2Cl2, 8:1) to afford 15 (58.4 mg,
1
0.7 Hz, 1H), δ 7.20 (d,
Hz, 1H), δ 5.93ꢀ5.83 (m, 1H), δ 5.31 (dd,
δ 5.15 (dd, = 10, 1.0 Hz, 1H), δ 3.71 (dt,
13C NMR (100 MHz, CDCl3): δ 179.8, 150.7, 146.1, 132.8, 2H); 13C NMR (100 MHz, CDCl3): δ 190.7, 136.5, 133.7,
J
= 3.6 Hz, 1H), δ 6.54 (dd,
= 16.9, 1.3 Hz, 1H), 7.97 (d,
= 6.9, 1.0 Hz, 2H); = 7.6 Hz, 2H), δ 3.71 (t,
J
= 3.6, 1.7 66% yield) as a colorless oil; H NMR (400 MHz, CDCl3): δ
= 7.3 Hz, 2H), δ 7.60 (t, = 7.4 Hz, 1H), δ 7.47 (t,
= 7.1 Hz, 2H), δ 3.43 (t, = 7.2 Hz,
J
J
J
J
J
J
J
J
118.2, 115.6, 112.2, 30.9; IR (KBr):
ν = 3135, 3085, 2924, 128.7, 127.3, 42.7, 31.2.
1652, 1567, 1467, 1385, 1150 cmꢀ1; HRMS (EI) m/z: [M]+
calcd. for C8H8O2S: 168.0245, found: 168.0249.
S
-(3-oxocyclohexyl) benzothioate (16)22
To a solution of the benzoic anhydride (100.0 mg, 0.442 mmol,
1.0 equiv.) in DMF (0.1 M) was added Na2S2O3ꢁ5H2O (120.7
mg, 0.486 mmol, 1.1 equiv.) stirred at 70 C under nitrogen
S
-benzyl thiophene-2-carbothioate (10a)37
o
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atmosphere for 2 hours, then added 2ꢀcyclohexenꢀ1ꢀone (212.5
mg, 2.211 mmol, 5 equiv.) in DMF (0.067 M) to the solution
and still stirred at 70 oC under nitrogen atmosphere. The
resulting reaction mixture was stirred for 7 hours until the
reaction was complete as indicated by TLC. After the reaction
was completed, the mixture was extracted with ether for three
times and the combined organic layer was washed with brine,
dried over MgSO4, filtered and concentrated. The crude product
was then purified by column chromatography (hexane/EtOAc,
Acknowledgements
This work is supported by grants from the Ministry of Science
and Technology, Taiwan (Grant MOST 106ꢀ2113ꢀMꢀ005ꢀ006ꢀ
MY2). We also thank for the support from the National Chung
Hsing University.
Notes and references
5:1) to afford 16 (62.9 mg, 61% yield) as a white solid; m. p.
1
(a) P. Chauhan, S. Mahajan, D. Enders, Chem. Rev., 2014,
114, 8807; (b) C. Shen, P. Zhang, Q. Sun, S. Bai, A. T. S.
Hor, X. Liu, Chem. Soc. Rev., 2015, 44, 291; (c) H. Liu, X.
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D. P. Nair, M. Podgórski, S. Charani, T. Gong, W. Xi, C. R.
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Máňez, Y. Yang, H. Lv, S. Li, Chem. Soc. Rev., 2013, 42,
6032.
1
82ꢀ83 oC; H NMR (400 MHz, CDCl3): δ 7.93 (d,
J
= 8.0 Hz,
2H), δ 7.58 (t,
J = 8.0 Hz, 1H), δ 7.45 (t, J = 7.8 Hz, 2H), δ
4.12ꢀ4.05 (m, 1H), δ 2.85ꢀ2.80 (m, 1H), δ 2.56ꢀ2.50 (m, 1H), δ
2.48ꢀ2.34 (m, 2H), δ 2.29ꢀ2.24 (m, 1H), δ 2.15ꢀ2.08 (m, 1H), δ
1.95ꢀ1.86 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 208.0,
190.5, 136.7, 133.6, 128.6, 127.2, 47.3, 41.6, 40.9, 31.2, 24.4.
2
3
4
N
-benzylbenzamide (17)39
To a solution of Sꢀbenzyl benzothioate (1a; 63.3 mg, 0.278
mmol, 1.0 equiv.) in DMF (0.3 M) was added benzylamine
(59.5 mg, 0.555 mmol, 2.0 equiv.) and K2CO3 (76.7 mg, 0.555
5
For selected examples, see: (a) V. Agarwal, S. Diethelm, L.
Ray, N. Garg, T. Awakawa, P. C. Dorrestein, B. S. Moore,
Org. Lett., 2015, 17, 4452; (b) F. Pan, Z.ꢀJ. Shi, ACS Catal.,
2014, 4, 280; (c) D. Crich, I. Sharma, Angew. Chem., Int. Ed.,
2009, 48, 7591; (d) K. Sasaki, D. Crich, Org. Lett., 2010, 12,
3254; (e) S. Magens, B. Plietker, Chem. Eur. J., 2011, 17,
8807; (f) S. Iimura, K. Manabe, S. Kobayashi, Chem.
Commun., 2002, 94; (g) H. Yang, H. Li, R. Wittenberg, M.
Egi, W. Huang, L. S. Liebeskind, J. Am. Chem. Soc., 2007,
129, 1132; (h) K. Kunchithapatham, C. C. Eichman, J. P.
Stambuli, Chem. Commun., 2011, 47, 12679; (i) K. Mal, I.
Das, Adv. Synth. Catal., 2017, 359, 2692; (j) P. M. M.
Shelton, C. E. Weller, C. Chattterjee, J. Am. Chem. Soc.,
2017, 139, 3946; (k) W. Yang, D. G. Drueckhammer, J. Am.
Chem. Soc., 2001, 123, 11004; (l) F. Nagaike, Y. Onuma, C.
Kanazawa, H. Hojo, A. Ueki, Y. Nakahara, Y. Nakahara,
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Anderson, Org. Lett., 2004, 6, 4659; (n) B. L. Nilsson, L. L.
Kiessling, R. T. Raines, Org. Lett., 2000, 2, 1939; (o) M.
Arisawa, M. Kuwajima, F. Toriyama, G. Li, M. Yamaguchi,
Org. Lett., 2012, 14, 3804; (p) D. L. Clive, S. Hisaindee, D.
M. Coltart, J. Org. Chem., 2003, 68, 9247.
For selected recent reviews, see: (a) J. Staunton, K.
Weissman, Nat. Prod. Rep., 2001, 18, 380; (b) H. M. Burke,
L. McSweeney, E. M. Scanlan, Nat. Commun., 2017, 8,
15655; (c) N. A. Mcgrath, R. T. Raines, Acc. Chem. Res.,
2011, 44, 752.
(a) M. J. Janssen "Carboxylic Acids and Esters" in PATAI's
Chemistry of Functional Groups: Carboxylic Acids and
Esters, Saul Patai, Ed. John Wiley, 1969, New York: pp. 705;
(b) A. Zieba, K. Suwinska, Heterocycles, 2008, 75, 2649; (c)
M. J. Petersson, C. Marchal, W. A. Loughlin, I. D. Jenkins, P.
C. Healy, A. Almesåker, Tetrahedron, 2007, 63, 1395.
(a) B. Neises, W. Steglich, Angew. Chem., Int. Ed., 1978, 17,
522; (b) S. Masamune, S. Kamata, J. Diakur, Y. Sugihara, G.
S. Bates, Can. J. Chem., 1975, 53, 3693.
o
mmol, 2.0 equiv.) stirred at 50 C under nitrogen atmosphere
for 24 hours. After the reaction was completed, the mixture was
extracted with EtOAc for three times and the combined organic
layer was washed with brine, dried over MgSO4, filtered and
concentrated. The crude product was then purified by column
chromatography (hexane/EtOAc, 3:1) to afford 17 (38.5 mg,
1
66% yield) as a white solid; m. p. 104ꢀ105 oC; H NMR (400
MHz, CDCl3): δ 7.79 (d,
J = 7.2 Hz, 2H), δ 7.51 (t, J = 7.4 Hz,
1H), δ 7.43 (t,
1H), δ 4.66 (d,
J
J
= 7.5 Hz, 2H), δ 7.37ꢀ7.28 (m, 5H), δ 6.38 (br,
= 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
167.4, 138.2, 134.3, 131.5, 128.7, 128.5, 127.8, 127.5, 126.9,
44.0.
1,3-diphenylprop-2-yn-1-one (18)40
A solution of the Sꢀbenzyl benzothioate (1a; 60.5 mg, 0.265
mmol, 1.0 equiv.), PdCl2(PPh3)2 (18.6 mg, 0.0265 mmol, 10
mol%), CuI (101.1 mg, 0.531 mmol, 2.0 equiv.)
triphenylphosphine (17.4 mg, 0.0663 mmol, 25 mol%), Et3N
(95.7 ꢂL) and phenylacetylene (54.2 mg, 0.531 mmol, 2.0
equiv.) in DMF (0.55 M) was stirred at 50 oC for 10 hours.
After the reaction was completed, the mixture was diluted with
EtOAc, and quenched with H2O. The mixture was filtered
through a pad of Celite and the filtrate was partitioned. The
aqueous layer was extracted with EtOAc for 3 times. The
combined organic layer was washed with brine, dried over
MgSO4, filtered and concentrated. The crude product was then
purified by column chromatography (hexane/EtOAc, 30:1) to
6
7
8
9
1
afford 18 (37.3 mg, 68% yield) as a brown oil; H NMR (400
MHz, CDCl3): δ 8.23 (d,
δ 7.64 (t,
J = 7.2 Hz, 2H), δ 7.71ꢀ7.68 (m, 2H),
A. R. Katrizky, A. A. Shestopalov, K. Suzuki, Synthesis
,
J
= 7.4 Hz, 1H), δ 7.55ꢀ7.47 (m, 3H), δ 7.45ꢀ7.41 (m,
2004, 1806.
2H); 13C NMR (100 MHz, CDCl3): δ 178.0, 136.8, 134.1,
133.0, 130.8, 129.5, 128.63, 128.57, 120.1, 93.1, 86.9.
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Conflicts of interest
There are no conflicts of interest to declare
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ARTICLE
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We have developed oneꢀpot reaction to provide thioester
derivatives via sodium thiosulfate as sulfur source under
transition metalꢀfree condition.
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