Synthesis of Sulfones and Sulfonamides via Sulfinate Anions: Revisiting the Utility of Thiosulfonates

Article abstract of DOI:10.1021/acs.joc.6b03016

Simple and high-yielding strategies for the production of a variety of sulfones and sulfonamides, using thiosulfonates synthesized by copper-catalyzed aerobic dimerization, are reported. Although thiosulfonates are an old class of compound, practical methods for their synthesis and utilization have not been rigorously developed. In this study, we revisit the reactions of easily accessible thiosulfonates to form sulfinate anions. Because of the similar reactivity of thiosulfonates and metal sulfinates derived from toxic SO₂, thiosulfinates are proposed to be stable, nontoxic alternatives to metal sulfinate salts.

Full text of DOI:10.1021/acs.joc.6b03016

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Article
Synthesis of Sulfones and Sulfonamides via Sulfinate
Anions: Revisiting the Utility of Thiosulfonates
Pranab Shyam, and Hye-Young Jang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b03016 • Publication Date (Web): 12 Jan 2017
Downloaded from http://pubs.acs.org on January 13, 2017
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Synthesis of Sulfones and Sulfonamides via Sulfinate
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Anions: Revisiting the Utility of Thiosulfonates
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Pranab K. Shyam, HyeꢀYoung Jang*
Department of Energy Systems Research, Ajou University, Suwon 16499, Korea
Email address: hyjang2@ajou.ac.kr
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ABSTRACT. Simple and highꢀyielding strategies for the production of a variety of sulfones and
sulfonamides, using thiosulfonates synthesized by copperꢀcatalyzed aerobic dimerization, are reported.
Although thiosulfonates are an old class of compound, practical methods for their synthesis and
utilization have not been rigorously developed. In this study, we revisit the reactions of easily accessible
thiosulfonates to form sulfinate anions. Due to the similar reactivity of thiosulfonates and metalꢀ
sulfinates derived from toxic SO2, thiosulfinates are proposed to be stable, nonꢀtoxic alternatives to
metalꢀsulfinate salts.
Introduction
Sulfinates are versatile reagents that are used in transitionꢀmetal catalyzed crossꢀcoupling reactions to
produce synthetically and pharmaceutically useful sulfones and sulfonamides.1,2 Although sulfinates
were reported in the early 1900s, their use in chemical reactions has drawn little attention due to the
limited accessibility of sulfinate reagents. Until DABSO (DABCO⋅(SO2)2; DABCO = 1,4ꢀ
diazabicyclo[2.2.2]octane) and potassium metabisulfite (K2S2O5) were introduced in metalꢀcatalyzed
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coupling reactions, the main sources of sulfinates were commercially available sodium sulfinates and
SO2 gasꢀderived sulfinates.3ꢀ5 The limited commercial availability of sodium sulfinates and the toxicity
of SO2 gas used for the generation of metalꢀsulfinates6 has resulted in the slow growth of sulfinate
chemistry. Since Willis and Mascitti introduced stable, nonꢀtoxic sulfinates, generated from DABSO
and K2S2O5, a range of sulfinate derivatives and their reactions have been extensively reported.7
In their pioneering work, Barton and coworkers studied the preparation and synthetic utility of alkyl Sꢀ
pyridyl thiosulfonates (Scheme 1).8 These intermediates were synthesized from aliphatic esters of Nꢀ
hydroxyꢀ2ꢀthiopyridone esters and SO2 gas under anaerobic cryogenic photolytic conditions. The
thiosulfonates were then treated with alkyl halides or Nꢀhaloamines (generated in situ from amines), to
form sulfones and sulfonamides, respectively. Lately, our research group has reported oneꢀpot copperꢀ
catalyzed aerobic coupling reactions using thiols to prepare synthetically challenging organosulfur
compounds.9 In particular, it was found that alkyl and aryl thiols undergo copperꢀcatalyzed oxidative
dimerization to form thiosulfonates.9e We envisioned that the latter could be cleaved by nucleophiles to
generate sulfinate anions, which would then react in one pot with various electrophiles to afford sulfones,
or with amines to form sulfonamides. Thus, in this study we present a new strategy for the preparation of
alkyl and aryl sulfones and sulfonamides based on the use of thiosulfonate intermediates. Compared
with the Barton’s protocol, it avoids using toxic SO2 gas, anaerobic cryogenic photolytic conditions, and
the preparation of Nꢀhydroxyꢀ2ꢀthiopyirdone esters. In addition, it expands the scope of the
thiosulfonatesꢀbased transformations to the aromatic chemical space.10 Taking into account their ready
accessibility and nonꢀhazardous properties, the proposed use of thiosulfonates provides a practical
platform for convenient synthesis of a variety of sulfones and sulfonamides without isolation of sulfinate
salts.
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Barton's synthesis of aliphatic sulfones and sulfonamides (1988, Ref. 8):
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O
SO2
O
O
N
S
Alk
O
Alk
S
N
S
SO2Cl2
or CCl4Br2
RX/KOH
amines
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O
O
O
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S
S
Alk
R
Alk
NR2
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A new strategy for practical synthesis of aliphatic and aromatic sulfonyl
products from thiols under environmentally benign conditions:
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Cu catalyst
O2
O
O
(2016, Ref. 9e)
R-SH
S
R
SR
O
O
This work:
E = AlkX, Ph2IOTf,
2-chlorobenzothiazole
S
E
R
R'
R' = Alk, Ar
O
O
Cs2CO3
amine
S
R
SR
O
O
NBS
R = Alk, Ar
S
R
NR2
Scheme 1 Synthesis of sulfones and sulfonamides via thiosulfonate intermediates.
Results and Discussion
The reaction of phenyl thiosulfonate 1a and benzyl bromide 1b was investigated in the presence of
organic and inorganic bases (Table 1). Firstly, guanidine and amidineꢀtype bases such as, 1,5,7ꢀ
triazabicyclo[4.4.0]decꢀ1ꢀene (TBD), 1,8ꢀdiazabicyclo[5.4.0]undecꢀ7ꢀene (DBU), 1,1,3,3ꢀ
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tetramethylguanidine (TMG), and 7ꢀmethylꢀ1,5,7ꢀtriazabicyclo[4.4.0]decꢀ5ꢀene (MeꢀTBD) were
examined. As listed in Table 1, the reaction in the presence of TBD afforded 1c in the highest yield
(entries 1ꢀ4). Diisopropylethyl amine (DIPEA), N,Nꢀdimethylaminopyridine (DMAP), and 1,4ꢀ
diazabicyclo[2.2.2]octane (DABCO) were also used in the reactions, affording 1c in good yields (entries
5ꢀ7). The inorganic bases K2CO3 and Cs2CO3 exerted very different effects, forming 1c in 5% and 97%
yields, respectively (entries 8 and 9). We next turned our attention to solvent effects. Using TBD, 1c was
formed in yields of 91% in CH3CN, 99% in THF, and 87% in EtOH (entries 10ꢀ12). Using Cs2CO3,
yields of 99% (EtOH) and 91% (THF) were obtained for 1c (entries 13 and 14). As almost complete
conversion was observed with 2 equiv. of bases, lower amounts of base (TBD and Cs2CO3) were also
tested. Using 1 equiv. of Cs2CO3, the excellent yield of 1c was retained, but 1 equiv. of TBD and 0.5
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equiv. of Cs2CO3 gave somewhat reduced yields (entries 15 and 16). The reaction was run at room
temperature, showing a slightly decreased yield (88%, entry 17).
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Table 1 Optimization of the synthesis of 1c
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Based on the results listed in Table 1, we next turned our attention to explore the substrate scope
under two sets of optimum reaction conditions, namely Cs2CO3 in EtOH, and TBD in THF. A range of
electrophiles including benzyl bromide derivatives, alkyl bromides, allyl bromide, αꢀbromo ketones and
esters, 2ꢀchlorobenzothioazole, and diphenyl iodonium salts, were examined for arylꢀ and alkyl sulfone
formation, as shown in Figure 1.
3ꢀMethoxy and 4ꢀfluoro benzyl bromides reacted with thiosulfonate 1a to afford sulfones 2c and 3c,
respectively, in excellent yields under Cs2CO3ꢀ and TBDꢀmediated reaction conditions. Meanwhile, the
reactions of 3,5ꢀbis(trifluoromethyl)ꢀbenzyl bromide gave comparatively low yields of 4c. Interestingly,
2ꢀnitroꢀbenzyl bromide afforded the desired sulfone 5c, along with the sideꢀproduct 5d, resulting from
sulfenylation, in good yields, but in ratios that depended on the reaction conditions. Presumably, the
higher acidity of 5c, assisted by the NO2 group, promoted further sulfenylation. In the presence of
acetylacetone, sulfenylation was completely inhibited to afford 5c as a single product in 94% yield. As
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alkyl derivatives, octyl bromide and methyl bromide were also tested, affording the desired products 6c
and 7c, respectively, in excellent yields. When allyl bromide was employed in this transformation, allylꢀ
substituted sulfone 8c was formed, along with vinyl sulfone 8d, when Cs2CO3 was used as the base.
Presumably, the acidic nature of the αꢀprotons in the allylsulfones induced the formation of the vinyl
sulfone.11 Interestingly, once again, the addition of acetylacetone promoted the formation of 8c only. βꢀ
Keto sulfones were prepared from thiosulfonates using αꢀbromo ketones and esters.12 Similar to the
reactions of 2ꢀnitroꢀbenzyl bromides, βꢀketo sulfone 9c and αꢀsulfenylated 9d were isolated. The
formation of 9d is the result of the displacement of the sulfinate moiety at the divalent sulfur atom of the
thiosulfonate with a carbon nucleophile of the desired product. Depending on the reaction conditions, 9c
or 9d could be formed as the major product. αꢀMethylated βꢀketo sulfone 10c and βꢀester 11c did not
undergo further sulfenylation. Heterocyclic and aromatic sulfones were synthesized using 2ꢀ
chlorobenzothiazole and diphenyliodonium triflate, respectively. The reaction of thiosulfonate 1a with
2ꢀchlorobenzothiazole afforded the desired heterocyclic sulfone 12c in good yields. The phenyl cation,
generated from diphenyliodonium triflate, also participated in these reactions, to give the desired
diphenyl sulfone 13c in good yields. The reaction of bromobenzene as an example of aromatic halides
was tested, resulting in no product formation.
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Figure 1. Sulfone substrate scope
Subsequent to electrophile screening, the nucleophilic reactivities of these diverse thiosulfonates were
assessed (Figure 2). Various thiosulfonates were subjected to the baseꢀmediated reaction with benzyl
bromide 1b. The methoxyꢀsubstituted thiosulfonate was converted into 14c in 94% yield using Cs2CO3,
but the TBDꢀmediated reaction was not as effective. A methylꢀsubstituted thiosulfonates participated in
the reaction with 1b to afford 15c in excellent yields for each base. Fluoroꢀ and chloroꢀsubstituted
thiosulfonates reacted to form sulfone 16c and 17c, respectively, in good yields, but slightly lower than
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those of the methylꢀsubstituted derivative. As an example of an aliphatic system, octylthiosulfonate was
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Figure 2 Examples of sulfones synthesized from various thiosulfonates and 1b
Next, the reactions of thiosulfonate 1a and morpholine 1e were attempted in the presence of Cs2CO3
(1 equiv.) and Nꢀbromosuccinimide (NBS) (Table 2). As shown during the formation of the sulfones
(above), Cs2CO3 (1 equiv.) provided generally good yields under most reaction conditions. Hence, we
used Cs2CO3 throughout the optimization of the sulfonamide synthesis. To induce halogenation, NBS (2
equiv.) was added in various solvents (DMSO, DMF, EtOH, CH3CN, THF, DCE, and toluene; entries 1ꢀ
7). In EtOH, 1f was obtained in the highest yield (96%, entry 3). When I2 was used instead of NBS, a
comparable yield was obtained (92%, entry 8). The reaction using Nꢀchlorosuccinimide (NCS) also gave
the desired product 1f in 66% yield (entry 9). When the amounts of NBS and 1e were reduced to 1 and
1.1 equiv., respectively, the lower yields of 1f were observed, but in the presence of 1.5 equiv. of NBS
and 1e, the high yield of 1f observed in entry 3 was retained (98%) (entries 10ꢀ12). To investigate the
effect of temperature, the reaction was run at room temperature, and 1f was formed at 84% yield (entry
13).
Table 2 Optimization of the synthesis of 1f
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O
O
Cs2CO3 (1 equiv.)
O
O
HN
S
1
Ph
N
S
O
Ph
SPh
oxidant
solvent (0.5 M)
80 °C
O
2
1a
1e
2 equiv.
1f
3
1 equiv.
4
5
entry oxidant (equiv.) solvent
yield
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9
1
2
NBS (2)
NBS (2)
NBS (2)
NBS (2)
NBS (2)
NBS (2)
NBS (2)
I2 (2)
DMSO
DMF
40%
74%
96%
75%
61%
57%
46%
92%
66%
75%
3
EtOH
CH3CN
THF
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6
DCE
7
toluene
EtOH
EtOH
EtOH
8
9
NCS (2)
NBS (1)
NBS (2)
NBS (1.5)
NBS (2)
10
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13
EtOH 94%a(74%)b
EtOH
EtOH
98%a
84%c
a
b
1e
1e
1.5 equiv. of
,
1.1 equiv. of
c The reaction was run at room temperature.
Using the optimized reaction conditions listed in Table 2, various amines and thiosulfonates were
reacted to form sulfonamides (Figure 3). Cyclic and acyclic secꢀamines participated in the reaction to
afford the desired sulfonamides 2f, 3f, and 4f in good yields. The reactions of benzyl amine and butyl
amine with 1a provided the desired products 5f and 6f in slightly lower yields than was observed for the
secꢀamines. In the case of aromatic amines, aniline and 2ꢀamino pyridine were examined under the
reaction conditions. Both compounds underwent bromination on the aromatic ring, resulting in no SꢀN
bond formation. Various thiosulfonates were also subjected to the indicated oxidative amination with
morpholine to afford aromatic sulfonamides 7fꢀ10f in good to excellent yields.
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Figure 3 Substrate scope in the formation of sulfonamides
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Plausible mechanisms for these transformations are shown in Scheme 2. In the presence of Cs2CO3 in
EtOH or TBD in THF, nucleophilic bases attack the divalent sulfur atom to release the sulfinate anion,
which is trapped by a carbon electrophile to afford the corresponding sulfone.7 In the case of
sulfonamides, the amines undergo halogenation by NBS or I2, prior to addition by the sufinate anion,
which is supported by control experiments (Scheme 2).3q,13 When a solution containing a thiosulfonate
and NBS was stirred prior to the addition of morpholine, the desired product 1f was obtained in 7%
yield; however, when the reaction of morpholine and NBS was conducted prior to the addition of the
thiosulfonate, 1f was isolated in 87% yield. Because halogenation of amines occurs prior to the reaction
with sulfinate anions, sulfenamides formed by the addition of amines to divalent sulfur of thiosulfonates
were not observed.14
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Scheme 2 Mechanisms for sulfone and sulfonamide formation via sulfinate anions, and control
experiments
Conclusion
We have demonstrated that thiosulfonates participate in reactions with electrophiles and amines to
afford a range of sulfones and sulfonamides in good to excellent yields. In the presence of nucleophilic
bases, sulfinate anions are expelled during the reaction, which react then with benzyl bromides, alkyl
bromides, allyl bromide, phenacyl bromide, and electronꢀdeficient aromatic compounds to afford
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sulfones, while sulfonamides are formed in the presence of amines and NBS. Compared to metalꢀ
sulfinates derived from the reaction of organometallic compounds and SO2, thiosulfonates are easily
synthesized by catalytic aerobic dimerization, and show good reactivity with various electrophiles and
amines. Thiosulfonates are stable, nonꢀtoxic alternatives to metalꢀsulfinates.
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Experimental Section
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General procedure for the synthesis of thiosulfonates:9e
Thiophenol (159 ꢁl, 1.5 mmol) and benzyl alcohol (52 ꢁl, 0.50 mmol) were added to a mixture of CuI
(4.8 mg, 0.025 mmol) and 1,5,7ꢀtriazabicyclo[4.4.0] decꢀ5ꢀene (TBD) (7.1 mg, 0.05 mmol) in THF (1
mL). The resulting solution was stirred at 65 °C for 18 h under 1 atmosphere of oxygen. The reaction
mixture was cooled, and the solvent was removed. The residue was purified by column chromatography
on a silica gel eluting with hexane and ethyl acetate to afford the desired product.
General procedure for the synthesis of sulfones:
Method A: Benzyl bromide (60 ꢁl, 0.50 mmol) was added to a mixture of Sꢀphenyl
benzenesulfonothiolate (62.6 mg, 0.25 mmol) and Cs2CO3 in a seal tube. After adding 0.5 ml of EtOH
to the reaction, the vessel was closed and stirred at 90 °C for 16 h. The reaction was cooled, diluted with
DCM and filtered. The filtrate was taken and concentrated through a rotary evaporator. The residue was
purified by column chromatography on a silica gel column eluting with 3 % ethyl acetate in hexane to
afford the desired product. [Depending on the nature of carbon electrophiles and amines, Cs2CO3 was
used either 1 equiv. or 2 equiv. (with respect to the thiosulfonate) to obtain the optimum yield.]
Method B: Benzyl bromide (60 ꢁl, 0.50 mmol) was added to a mixture of Sꢀphenyl
benzenesulfonothiolate (62.6 mg, 0.25 mmol) and 1,5,7ꢀtriazabicyclo[4.4.0] decꢀ5ꢀene (TBD) in a seal
tube. After addition of 0.5 ml THF the reaction vessel was closed and stirred at 65 °C for 16 h. The
reaction was cooled and concentrated through a rotary evaporator. The residue was purified by column
chromatography on a silica gel column eluting with 3 % ethyl acetate in hexane to afford the desired
product. [Depending on the nature of carbon electrophiles and amines, TBD was used either 1 equiv. or
2 equiv. (with respect to the thiosulfonate) to obtain the optimum yield.]
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(Benzylsulfonyl)benzene (1c):15 The representative experimental procedures were applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with benzyl bromide (60 ꢁl, 0.50 mmol) to form
1c as white solid. Mp: 148ꢀ150 °C. 1H NMR (CDCl3, 400 MHz): 7.63ꢀ7.56 (3H, m), 7.45ꢀ7.41 (2H, m),
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7.33ꢀ7.22 (3H, m), 7.08 (2H, d, J = 8.0 Hz), 4.30 (2H, s). C{1H}NMR (CDCl3, 100 MHz) δ: 137.7,
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133.6, 130.7, 128.8, 128.7, 128.6, 128.5, 128.0, 63.0. HRMS (EI, m/z): calcd for C13H12O2S [M]+,
232.0558; found, 232.0555. FTIR (neat): 3030, 2963, 1302, 1152, 1126 cmꢀ1.
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1-Methoxy-3-((phenylsulfonyl)methyl)benzene (2c):16 The representative experimental procedures
were applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 3ꢀmethoxybenzyl bromide
(71 ꢁl, 0.50 mmol) to form 2c as white solid. Mp: 112ꢀ114 °C. 1H NMR (CDCl3, 400 MHz): 7.66ꢀ7.58
(3H, m), 7.47ꢀ7.44 (2H, m), 7.15 (1H, t, J = 8.0 Hz), 6.86ꢀ6.83 (1H, m), 6.65ꢀ6.60 (2H, m), 4.28 (2H, s),
13
3.71(3H, s). C{1H}NMR (CDCl3, 100 MHz): 159.4, 137.8, 133.6, 129.5, 129.3, 128.8, 128.6, 123.1,
115.9, 114.7, 62.9, 55.3 ppm. HRMS (FAB, m/z): calcd for C14H15O3S [M+H]+, 263.0742; found,
263.0741. FTIR (neat): 3061, 2977, 1299, 1132 cmꢀ1.
1-Fluoro-4-((phenylsulfonyl)methyl)benzene (3c):17 The representative experimental procedures
were applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 4ꢀfluorobenzyl bromide (63
ꢁl, 0.50 mmol) to form 3c as white solid. Mp: 167ꢀ168 °C. 1H NMR (CDCl3, 400 MHz): 7.65ꢀ7.59 (3H,
13
m), 7.49ꢀ7.45 (2H, m), 7.08ꢀ7.04 (2H, m), 6.97ꢀ6.93 (2H, m), 4.28 (2H, s). C{1H}NMR (CDCl3, 100
MHz): 164.2 (d, J = 246 Hz), 137.7, 133.8, 132.6 (d, J = 9.1 Hz), 129.0, 128.6, 124.0, 115.8 (d, J = 22
Hz), 62.1. HRMS (FAB, m/z): calcd for C13H12FO2S [M+H]+, 251.0542; found, 251.0540. FTIR (neat):
3061, 2945, 1303, 1150 cmꢀ1.
1-((Phenylsulfonyl)methyl)-3,5-bis(trifluoromethyl)benzene (4c): The representative experimental
procedures were applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 3,5ꢀ
1
Bis(trifluoromethyl)benzyl bromide (96 ꢁl, 0.50 mmol) to form 4c as white solid. Mp: 147ꢀ149 °C. H
NMR (CDCl3, 400 MHz): 7.84 (1H, s), 7.69ꢀ7.64 (3H, m), 7.53ꢀ7.49 (4H, m), 4.41 (2H, s).
13C{1H}NMR (CDCl3, 100 MHz): 137.0, 134.4, 132.0 (q, J = 33.4 Hz), 130.9 (2C), 129.3, 128.5, 122.8
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(q, J = 271 Hz), 122.7 (m), 62.1. HRMS (FAB, m/z): calcd for C15H11F6O2S [M+H]+, 369.0384; found,
1
2
3
369.0385. FTIR (neat,): 3061, 2932, 1330, 1128 cmꢀ1.
4
5
6
1-Nitro-2-((phenylsulfonyl)methyl)benzene
(5c),
and
((2-
7
8
9
nitrophenyl)(phenylsulfonyl)methyl)(phenyl)sulfane (5d): The representative experimental
procedures were applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 2ꢀnitrobenzyl
bromide (110 mg, 0.50 mmol) to afford the easily separable mixture of 5c and 5d. 1-nitro-2-
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1
((phenylsulfonyl)methyl)benzene (5c):18 Mp (light yellow solid): 114ꢀ116 °C. H NMR (CDCl3, 400
MHz): 7.97 (1H, dd, J = 8.0, 1.2 Hz), 7.69ꢀ7.66 (2H, m), 7.64ꢀ7.59 (2H, m), 7.55ꢀ7.44 (4H, m), 4.94
13
(2H, s). C{1H}NMR (CDCl3, 100 MHz) δ: 149.2, 137.8, 134.2, 134.1, 133.3, 130.1, 129.2, 128.3,
125.4, 122.9, 58.7. HRMS (FAB, m/z): calcd for C13H12NO4S [M+H]+, 278.0487; found, 278.0485.
FTIR
(neat):
3068,
2924,
1529,
1352,
1320,
1147
cmꢀ1.
((2-
1
nitrophenyl)(phenylsulfonyl)methyl)(phenyl)sulfane (5d): Mp (yellow solid): 116ꢀ118 °C. H NMR
(CDCl3, 400 MHz): 7.96 (1H, d, J = 8.0 Hz), 7.92 (1H, d, J = 8.4 Hz), 7.75ꢀ7.68 (3H, m), 7.61ꢀ7.51
13
(2H, m), 7.43 (2H, t, 7.2 Hz), 7.30ꢀ7.19 (5H, m), 6.65 (1H, d, J = 1.6 Hz). C{1H}NMR (CDCl3, 100
MHz): 148.6, 136.8, 134.2, 133.4, 132.5, 132.3, 132.2, 130.1, 129.3 (2C), 128.9, 128.8, 127.0, 124.9,
70.2. HRMS (FAB, m/z): calcd for C19H16NO4S2 [M+H]+, 386.0521; found, 386.0518. FTIR (neat):
3065, 2919, 1528, 1348, 1322, 1150 cmꢀ1.
(Octylsulfonyl)benzene (6c):19 The representative experimental procedures were applied to Sꢀphenyl
benzenesulfonothiolate (62.6 mg, 0.25 mmol) with octyl bromide (88 ꢁl, 0.50 mmol) to afford 6d as
1
liquid. H NMR (CDCl3, 400 MHz): 7.92 (2H, dd, J = 8.0, 1.6 Hz), 7.68ꢀ7.63 (1H, m), 7.59ꢀ7.55 (2H,
13
m), 3.10ꢀ3.06 (2H, m), 1.74ꢀ1.67 (2H, m), 1.36ꢀ1.23 (10H, m), 0.86 (3H, t, J = 7.2 Hz). C{1H}NMR
(CDCl3, 100 MHz): 139.1, 133.5, 129.2, 127.9, 56.4, 31.8, 29.1, 29.0, 28.4, 22.8, 22.7, 14.2. HRMS
(FAB, m/z): calcd for C14H23O2S [M+H]+, 255.1419; found, 255.1418. FTIR (neat): 3065, 2927, 1306,
1147 cmꢀ1.
(Methylsulfonyl)benzene (7c):15 The representative experimental procedures were applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with methyl iodide (32 ꢁl, 0.50 mmol) to form 7c
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1
as white solid. Mp: 87ꢀ89 °C. H NMR (CDCl3, 400 MHz): 7.96 (2H, dd, J = 8.4, 0.8 Hz), 7.69ꢀ7.64
(1H, m), 7.60ꢀ7.56 (2H, m), 3.06 (3H, s). 13C{1H}NMR (CDCl3, 100 MHz): 140.4, 133.6, 129.3, 127.2,
44.6. HRMS (FAB, m/z): calcd for C7H9O2S [M+H]+, 157.0323; found, 157.0322. FTIR (neat): 3023,
2927, 1307, 1147 cmꢀ1.
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2
3
4
5
6
7
8
9
(Allylsulfonyl)benzene (8c) and (prop-1-en-1-ylsulfonyl)benzene (8d): The representative
experimental procedures were applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with
allyl bromide (45 ꢁl, 0.50 mmol) to form the inseparable liquid mixture of 8c and 8d.20
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1
(Allylsulfonyl)benzene (8c): H NMR (CDCl3, 400 MHz): 7.89 (2H, dd, J = 8.4, 1.2 Hz), 7.68ꢀ7.63
(1H, m), 7.59ꢀ7.54 (2H, m), 5.85ꢀ5.74 (1H, m), 5.36 (1H, dd, J = 10.0, 4.8 Hz), 5.18ꢀ5.12 (1H, m), 3.83
13
(2H, dd, J = 7.6, 0.8 Hz). C{1H}NMR (CDCl3, 100 MHz): 138.1, 133.7, 128.9, 128.3, 124.7, 124.5,
60.9. HRMS (FAB, m/z): calcd for C9H11O2S [M+H]+,183.0480; found, 183.0478. FTIR (neat): 3066,
2920, 1308, 1146 cmꢀ1.
1-Phenyl-2-(phenylsulfonyl)ethan-1-one (9c) + 1-Phenyl-2-(phenylsulfonyl)-2-(phenylthio)ethan-
1-one (9d): The representative experimental procedures were applied to Sꢀphenyl
benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 2ꢀbromoacetophenone (102 mg, 0.50 mmol) to form
the easily separable mixture of 9c and 9d as white solid. 1-phenyl-2-(phenylsulfonyl)ethan-1-one
1
(9c):21 Mp: 95ꢀ97 °C. H NMR (CDCl3, 400 MHz): 7.95ꢀ7.88 (4H, m), 7.68ꢀ7.59 (2H, m), 7.56ꢀ7.52
(2H, m), 7.50ꢀ7.45 (2H, m), 4.74 (2H, s). 13C{1H}NMR (CDCl3, 100 MHz): 187.8, 138.6, 135.6, 134.3,
134.1, 129.2, 129.1, 128.8, 128.4, 63.4. HRMS (FAB, m/z): calcd for C14H13O3S [M+H]+, 261.0585;
found, 261.0583. FTIR (neat): 3064, 2947, 1680, 1323, 1154 cmꢀ1. 1-phenyl-2-(phenylsulfonyl)-2-
1
(phenylthio)ethan-1-one (9d):22 Mp: 135ꢀ136 °C. H NMR (CDCl3, 400 MHz): 8.02 (2H, dd, J = 8.4,
1.2 Hz), 7.89 (2H, d, J = 8.0 Hz), 7.70ꢀ7.44 (8H, m), 7.37ꢀ7.28 (3H, m), 5.79 (1H, s). 13C{1H}NMR
(CDCl3, 100 MHz): 189.0, 136.3, 134.9, 134.4, 134.3, 133.5, 131.9, 130.6, 129.4, 129.3, 129.1, 128.8,
128.6, 75.6. HRMS (FAB, m/z): calcd for C20H17O3S2 [M+H]+, 369.0619; found, 369.0618. FTIR
(neat): 3062, 1682, 1323, 1151 cmꢀ1.
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1-Phenyl-2-(phenylsulfonyl)propan-1-one (10c):23 The representative experimental procedures were
applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 2ꢀbromopropiophenone (78 ꢁl,
1
2
3
4
5
6
1
0.50 mmol) to form 10c as white solid. Mp: 78ꢀ80 °C. H NMR (CDCl3, 400 MHz): 7.98 (2H, dd, J =
7
8
9
7.2, 1.2 Hz), 7.80 (2H, dd, J = 7.2, 1.2 Hz), 7.66ꢀ7.58 (2H, m), 7.54ꢀ7.45 (4H, m), 5.19 (1H, q, J = 6.8
Hz), 1.58 (3H, d, J = 7.2 Hz). 13C{1H}NMR (CDCl3, 100 MHz): 192.3, 136.1, 136.0, 134.2, 134.0,
129.7, 129.1, 128.9, 128.7, 65.1, 13.4. HRMS (EI, m/z): calcd for C15H14O3S [M]+, 274.0664; found,
274.0667. FTIR (neat): 3064, 2941, 1682, 1309, 1149 cmꢀ1.
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Benzyl 2-(phenylsulfonyl)acetate (11c): The representative experimental procedures were applied to
Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with benzyl bromoacetate (81 ꢁl, 0.50 mmol) to
afford 11c as liquid. 1H NMR (CDCl3, 400 MHz): 7.86 (2H, d, J = 8.0 Hz), 7.64 (1H, t, J = 7.6 Hz),
13
7.51ꢀ7.47 (2H, m), 7.36ꢀ7.34 (3H, m), 7.27ꢀ7.25 (2H, m), 5.11 (2H, s), 4.15 (2H, s). C{1H}NMR
(CDCl3, 100 MHz) δ: 162.1, 138.5, 134.4, 134.2, 129.2, 128.7, 128.6, 128.5, 128.4, 68.1, 61.1. HRMS
(EI, m/z): calcd for C15H14O4S [M]+, 290.0613; found, 290.0610. FTIR (neat): 3065, 2943, 1739, 1327,
1151 cmꢀ1.
2-(Phenylsulfonyl)benzo[d]thiazole(12c): The representative experimental procedures were applied
to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with 2ꢀchlorobenzothiazole (67 ꢁl, 0.50
1
mmol) to form 12c as white solid. Mp: 159ꢀ161 °C. H NMR (CDCl3, 400 MHz): 8.17ꢀ8.13 (3H, m),
7.96 (1H, dd, J = 7.6, 0.8 Hz), 7.68ꢀ7.64 (1H, m), 7.59ꢀ7.50 (4H, m). 13C{1H}NMR (CDCl3, 100 MHz):
167.1, 152.8, 138.4, 137.0, 134.5, 129.5, 128.9, 127.9, 127.5, 125.5, 122.2. HRMS (FAB, m/z): calcd for
C13H10NO2S2 [M+H]+, 276.0153; found, 276.0151. FTIR (neat): 3092, 3061, 1329, 1316, 1159 cmꢀ1.
Sulfonyldibenzene (13c):24 The representative experimental procedures were applied to Sꢀphenyl
benzenesulfonothiolate (62.6 mg, 0.25 mmol) with diphenyliodonium trifluoromethanesulfonate (220
1
mg, 0.50 mmol) to form 13c as white solid. Mp: 123ꢀ125 °C. H NMR (CDCl3, 400 MHz): 7.96ꢀ7.93
13
(4H, m), 7.58ꢀ7.48 (6H, m). C{1H}NMR (CDCl3, 100 MHz): 141.5, 133.2, 129.3, 127.6. HRMS
(FAB, m/z): calcd for C12H11O2S [M+H]+, 219.0480; found, 219.0479. FTIR (neat, cmꢀ1): 3065, 1309,
1154 cmꢀ1.
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1-(Benzylsulfonyl)-4-methoxybenzene (14c):25 The representative experimental procedures were
applied to Sꢀ4ꢀmethoxyphenyl 4ꢀmethoxybenzenesulfonothiolate (77.6 mg, 0.25 mmol) with benzyl
1
2
3
4
5
6
1
bromide (60 ꢁl, 0.50 mmol) to form 14c as white solid. Mp: 101ꢀ103 °C. H NMR (CDCl3, 400 MHz):
7
8
9
7.53 (2H, dd, J = 6.8, 2.0 Hz), 7.31ꢀ7.24 (3H, m), 7.09 (2H, d, J = 6.8 Hz), 6.89 (2H, dd, J = 6.8, 2.0
Hz), 4.28 (2H, s), 3.85 (3H, s). 13C{1H}NMR (CDCl3, 100 MHz): 163.6, 130.8, 130.7, 129.3, 128.6,
128.5, 128.4, 114.0, 63.2, 55.8. HRMS (EI, m/z): calcd for C14H14O3S [M]+, 262.0664; found, 262.0664.
FTIR (neat): 3031, 2975, 1315, 1296, 1153 cmꢀ1.
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1-(Benzylsulfonyl)-4-methylbenzene (15c):26 The representative experimental procedures were
applied to Sꢀpꢀtolyl 4ꢀmethylbenzenesulfonothioate (69.6 mg, 0.25 mmol) with benzyl bromide (60 ꢁl,
0.50 mmol) to form 15c as white solid. Mp: 146ꢀ148 °C. 1H NMR (CDCl3, 400 MHz): 7.50 (2H, d, J =
8.4 Hz), 7.32ꢀ7.22 (5H, m), 7.09 (2H, d, J = 6.8 Hz), 4.28 (2H, s), 2.41 (3H, s). 13C{1H}NMR (CDCl3,
100 MHz) δ: 144.6, 134.9, 130.8, 129.4, 128.6, 128.5, 128.4, 128.2, 62.9, 21.8. HRMS (EI, m/z): calcd
for C14H14O2S [M]+, 246.0715; found, 246.0714. FTIR (neat): 3031, 2974, 2924, 1303, 1155 cmꢀ1.
1-(Benzylsulfonyl)-4-fluorobenzene (16c):17 The representative experimental procedures were
applied to Sꢀ4ꢀfluorophenyl 4ꢀfluorobenzenesulfonothioate (71.6 mg, 0.25 mmol) with benzyl bromide
(60 ꢁl, 0.50 mmol) to form 16c as white solid. Mp: 155ꢀ157 °C. 1H NMR (CDCl3, 400 MHz): 7.63ꢀ7.59
(2H, m), 7.34ꢀ7.24 (3H, m), 7.13ꢀ7.06 (4H, m), 4.31 (2H, s). 13C{1H}NMR (CDCl3, 100 MHz): 166.9
(d, 54 Hz), 133.7 (d, J = 3.1 Hz), 131.5 (d, J = 9.1 Hz), 130.7, 128.8, 128.6, 127.9, 116.3 (d, J = 21.9
Hz), 63.1. HRMS (EI, m/z): calcd for C13H11FO2S [M]+, 250.0464; found, 250.0463. FTIR (neat): 3057,
2942, 1315, 1149, 1085 cmꢀ1.
1-(Benzylsulfonyl)-4-chlorobenzene (17c):25 The representative experimental procedures were
applied to Sꢀ4ꢀchlorophenyl 4ꢀchlorobenzenesulfonothioate (79.8 mg, 0.25 mmol) with benzyl bromide
(60 ꢁl, 0.50 mmol) to form 17c as white solid. Mp: 144ꢀ146 °C. 1H NMR (CDCl3, 400 MHz): 7.54 (2H,
dd, J = 8.8, 2.0 Hz), 7.41 (2H, dd, J = 8.8, 2.4 Hz), 7.35ꢀ7.25 (3H, m), 7.09 (2H, d, J = 7.6 Hz), 4.31
13
(2H, s). C{1H}NMR (CDCl3, 100 MHz) δ: 140.4, 136.2, 130.8, 130.1, 129.2, 128.9, 128.7, 127.8,
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63.0. HRMS (EI, m/z): calcd for C13H11ClO2S [M]+, 266.0168; found, 266.0172. FTIR (neat): 3065,
2943, 1314, 1151 cmꢀ1.
1
2
3
4
5
6
7
8
((Octylsulfonyl)methyl)benzene (18c): The representative experimental procedures were applied to
Sꢀoctyl octaneꢀ1ꢀsulfonothiolate (80.6 mg, 0.25 mmol) with benzyl bromide (60 ꢁl, 0.50 mmol) to form
9
1
18c as white solid. Mp: 70ꢀ72 °C. H NMR (CDCl3, 400 MHz): 7.41ꢀ7.38 (5H, m), 4.22ꢀ4.19 (2H, m),
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13
2.82ꢀ2.78 (2H, m), 1.81ꢀ1.75 (2H, m), 1.36ꢀ1.25 (10H, m), 0.87 (3H, t, J = 5.6 Hz). C{1H}NMR
(CDCl3, 100 MHz): 130.5, 129.0, 128.9, 128.1, 59.5, 51.2, 31.9, 29.2, 29.1, 28.6, 22.8, 22.0, 14.3.
HRMS (EI, m/z): calcd for C15H24O2S [M]+, 268.1497; found, 268.1500. FTIR (neat): 3025, 2954, 2916,
1317, 1299, 1123 cmꢀ1.
General procedure for the synthesis of sulfonamides: Morpholine (44 ꢁl, 0.50 mmol) was added to
a mixture of Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol), NBS (90 mg, 0.5 mmol) and
Cs2CO3 (82.2 mg, 0.25 mmol) in 0.5 ml of EtOH in a seal tube. The tube was closed and stirred at 80 °C
for 16 h. After completion of the reaction, it was cooled, diluted with DCM and filtered. Filtrate was
concentrated through a rotary evaporator and purified by column chromatography on a silica gel column
eluting with 6 % ethyl acetate in hexane to afford the desired product.
4-(Phenylsulfonyl)morpholine (1f):27 The representative experimental procedure was applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with morpholine (44 ꢁl, 0.50 mmol) to obtained 1f
1
as white solid in 96 % yields. Mp: 119ꢀ121 °C. H NMR (CDCl3, 400 MHz): 7.77ꢀ7.75 (2H, m), 7.65ꢀ
13
7.61 (1H, m), 7.58ꢀ7.54 (2H, m), 3.74 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz). C{1H}NMR
(CDCl3, 100 MHz): 135.0, 133.1, 129.1, 127.8, 66.2, 46.2. HRMS (EI, m/z): calcd for C10H13NO3S [M]+,
227.0616; found, 227.0617. FTIR (neat): 2921, 2856, 1449, 1350, 1169 cmꢀ1.
1-(Phenylsulfonyl)piperidine (2f):27 The representative experimental procedure was applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with piperidine (50 ꢁl, 0.50 mmol) to obtained 2f
as white solid in 95 % yields. Mp: 92ꢀ94 °C. 1H NMR (CDCl3, 400 MHz): 7.77ꢀ7.74 (2H, m), 7.61ꢀ7.57
(1H, m), 7.55ꢀ7.51 (2H, m), 2.99 (4H, t, J = 5.2 Hz), 1.67ꢀ1.61 (4H, m), 1.45ꢀ1.40 (2H, m).
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13C{1H}NMR (CDCl3, 100 MHz): 136.2, 132.5, 128.9, 127.6, 47.1, 25.4, 23.7. HRMS (EI, m/z): calcd
for C11H15NO2S [M]+, 225.0824; found, 225.0826. FTIR (neat): 2945, 2840, 1445, 1336, 1168 cmꢀ1.
1-(Phenylsulfonyl)pyrrolidine (3f):27 The representative experimental procedure was applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with pyrrolidine (42 ꢁl, 0.50 mmol) to obtained 3f
as white solid in 84 % yields. Mp: 52ꢀ54 °C. 1H NMR (CDCl3, 400 MHz): 7.86ꢀ7.81 (2H, m), 7.62ꢀ7.58
(1H, m), 7.57ꢀ7.51 (2H, m), 3.28ꢀ3.22 (4H, m), 1.79ꢀ1.72 (4H, m). 13C{1H}NMR (CDCl3, 100 MHz):
136.7, 132.5, 128.9, 127.4, 48.1, 25.4. HRMS (EI, m/z): calcd for C10H13NO2S [M]+, 211.0667; found,
211.0664. FTIR (neat): 2980, 2886, 1445, 1337, 1159 cmꢀ1.
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N-Benzyl-N-methylbenzenesulfonamide (4f):27 The representative experimental procedure was
applied to Sꢀphenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with Nꢀbenzylmethylamine (65 ꢁl,
1
0.50 mmol) to obtained 4f as white solid in 83 % yields. Mp: 91ꢀ93 °C. H NMR (CDCl3, 400 MHz):
13
7.85ꢀ7.83 (2H, m), 7.63ꢀ7.53 (3H, m), 7.35ꢀ7.25 (5H, m), 4.14 (2H, s), 2.60 (3H, s). C{1H}NMR
(CDCl3, 100 MHz) δ: 137.2, 135.5, 132.7, 129.1, 128.6, 128.3, 127.9, 127.4, 54.3, 34.5. HRMS (EI,
m/z): calcd for C14H15NO2S [M]+, 261.0824; found, 261.0822. FTIR (neat): 2968, 2860, 1446, 1341,
1166 cmꢀ1.
N-Benzylbenzenesulfonamide (5f):28 The representative experimental procedure was applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with benzylamine (55 ꢁl, 0.50 mmol) to obtained
5f as white solid in 65 % yields. Mp: 86ꢀ88 °C. 1H NMR (CDCl3, 400 MHz): 7.86ꢀ7.83 (2H, m), 7.58ꢀ
7.54 (1H, m), 7.50ꢀ7.45 (2H, m), 7.26ꢀ7.21 (3H, m), 7.18ꢀ7.15 (2H, m), 5.04 (1H, t, J = 6.0 Hz), 4.13
(2H, d, J = 6.4 Hz). 13C{1H}NMR (CDCl3, 100 MHz): 139.8, 136.1, 132.6, 129.1, 128.6, 127.9, 127.8,
127.0, 47.4. HRMS (EI, m/z): calcd for C13H13NO2S [M]+, 247.0667; found, 247.0669. FTIR (neat):
3284, 3064, 1447, 1326, 1160 cmꢀ1.
N-Butylbenzenesulfonamide (6f):28 The representative experimental procedures were applied to Sꢀ
phenyl benzenesulfonothiolate (62.6 mg, 0.25 mmol) with butylamine (50 ꢁl, 0.50 mmol) to obtained 6f
as colorless liquid in 66 % yields. 1H NMR (CDCl3, 400 MHz): 7.92ꢀ7.87 (2H, m), 7.60ꢀ7.56 (1H, m),
7.54ꢀ7.49 (2H, m), 4.74 (1H, bs), 2.97ꢀ2.92 (2H, m), 1.47ꢀ1.40 (2H, m), 1.33ꢀ1.24 (2H, m), 0.84 (3H, t,
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J = 7.2 Hz). 13C{1H}NMR (CDCl3, 100 MHz): 139.8, 132.6, 129.1, 127.0, 43.1, 31.8, 19.9, 13.8. HRMS
(EI, m/z): calcd for C10H15NO2S [M]+, 213.0824; found, 213.0821. FTIR (neat): 3284, 2960, 2873,
1447, 1325, 1161 cmꢀ1.
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4-((4-Fluorophenyl)sulfonyl)morpholine (7f):27 The representative experimental procedure was
applied to Sꢀ4ꢀfluorophenyl 4ꢀfluorobenzenesulfonothioate (71.6 mg, 0.25 mmol) with morpholine (44
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ꢁl, 0.50 mmol) to obtained 7f as white solid in 89 % yields. Mp: 103ꢀ105 °C. H NMR (CDCl3, 400
MHz): 7.80ꢀ7.76 (2H, m), 7.28ꢀ7.22 (2H, m), 3.75 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz).
13C{1H}NMR (CDCl3, 100 MHz): 166.5 (d, J = 253 Hz), 131.2 (d, J = 3.8 Hz), 130.5 (d, J = 9.1 Hz),
116.5 (d, J = 22 Hz), 66.1, 46.1. HRMS (EI, m/z): calcd for C10H12FNO3S [M]+, 245.0522; found,
245.0523. FTIR (neat): 2962, 2858, 1347, 1158 cmꢀ1.
4-((4-Chlorophenyl)sulfonyl)morpholine (8f):27 The representative experimental procedure was
applied to Sꢀ4ꢀchlorophenyl 4ꢀchlorobenzenesulfonothioate (79.8 mg, 0.25 mmol) with morpholine (44
1
ꢁl, 0.50 mmol) to obtained 8f as white solid in 86 % yields. Mp: 149ꢀ151 °C. H NMR (CDCl3, 400
MHz): 7.71ꢀ7.69 (2H, m), 7.55ꢀ7.53 (2H, m), 3.74 (4H, t, J = 4.8 Hz), 3.00 (4H, t, J = 4.8 Hz).
13C{1H}NMR (CDCl3, 100 MHz): 139.6, 133.5, 129.4, 129.2, 66.1, 46.1. HRMS (EI, m/z): calcd for
C10H12ClNO3S [M]+, 261.0226; found, 261.0229. FTIR (neat): 2978, 2866, 1453, 1350, 1163 cmꢀ1.
4-Tosylmorpholine (9f):27 The representative experimental procedure was applied to Sꢀpꢀtolyl 4ꢀ
methylbenzenesulfonothioate (69.6 mg, 0.25 mmol) with morpholine (44 ꢁl, 0.50 mmol) to obtained 9f
1
as white solid in 91 % yields. Mp: 149ꢀ151 °C. H NMR (CDCl3, 400 MHz): 7.64 (2H, d, J = 8.0 Hz),
7.35 (2H, d, J = 8.0 Hz), 3.73 (4H, t, J = 4.8 Hz), 2.98 (4H, t, J = 4.8 Hz), 2.44 (3H, s). 13C{1H}NMR
(CDCl3, 100 MHz) δ: 143.8, 131.8, 129.7, 127.8, 66.1, 46.1, 21.7. HRMS (EI, m/z): calcd for
C11H15NO3S [M]+, 241.0773; found, 241.0775. FTIR (neat): 2972, 2851, 1452, 1346, 1165 cmꢀ1.
4-((4-Methoxyphenyl)sulfonyl)morpholine (10f):27 The representative experimental procedure was
applied to Sꢀ4ꢀmethoxyphenyl 4ꢀmethoxybenzenesulfonothiolate (77.6 mg, 0.25 mmol) with morpholine
(44 ꢁl, 0.50 mmol) to obtained 10f as white solid in 95 % yields. Mp: 112ꢀ113 °C. 1H NMR (CDCl3, 400
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MHz): 7.70 (2H, d, J = 9.2 Hz), 7.02 (2H, d, J = 8.8 Hz), 3.88 (3H, s), 3.73 (4H, t, J = 4.8 Hz), 2.97
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(4H, t, J = 4.8 Hz). C{1H}NMR (CDCl3, 100 MHz): 163.0, 129.9, 126.3, 114.2, 66.1, 55.8, 46.1.
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HRMS (EI, m/z): calcd for C11H15NO4S [M]+, 257.0722; found, 257.0719. FTIR (neat): 2974, 2852,
1454, 1347, 1162 cmꢀ1.
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Acknowledgments. This study was supported by the C1 gas refinery program (No.
2015M3D3A1A01065436) through the National Research Foundation of Korea (NRF) and the Korea
Research Foundation (No. 2016R1D1A1A09917100).
Associated Content
Supporting Information. Spectroscopic data for products. This material is available free of charge via the
Internet at http://pubs.acs.org.
References.
1. For reviews regarding the synthesis of sulfones and sulphonamide involving sulfinates, see: (a)
Aziz, J.; Messaoudi, S.; Alami, M.; Hamze, A. Org. Biomol. Chem. 2014, 12, 9743ꢀ9759. (b)
Deeming, A. S.; Emmett, E. J.; RichardsꢀTaylor, C. S.; Willis, M. C. Synthesis 2014, 46, 2701ꢀ
2710. (c) Emmett, E. J.; Willis, M. C. Asian J. Org. Chem. 2015, 4, 602ꢀ611. (d) Liu, G.; Fan, C.;
Wu, J. Org. Biomol. Chem. 2015, 13, 1592ꢀ1599.
2. For selected articles of pharmaceutical use of sulfones and sulfonamides, see: (a) Drews, J. Science
2000, 287, 1960ꢀ1964. (b) Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.;
Masferrer, J. L.; Perkins, W. E.; Rogers, R. S.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.;
Seibert, K. J. Med. Chem. 2000, 43, 775ꢀ777. (c) Natarajan, A.; Guo, Y.; Harbinski, F.; Fan, Y. H.;
Chen, H.; Luus, L.; Diercks, J.; Aktas, H.; Chorev, M.; Halperin, J. A. J. Med. Chem. 2004, 47,
4979ꢀ4982. (d) Banerjee, M.; Poddar, A.; Mitra, G.; Surolia, A.; Owa, T.; Bhattacharyya, B. J.
Med. Chem. 2005, 48, 547ꢀ555. (e) Stearns, B. A.; Baccei, C.; Bain, G.; Broadhead, A.; Clark, R.
C.; Coate, H.; Evans, J. F.; Fagan, P.; Hutchinson, J. H.; King, C.; Lee, C.; Lorrain, D. S.; Prasit,
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Page 20 of 24
P.; Prodanovich, P.; Santini, A.; Scott, J. M.; Stock, N. S.; Truong, Y. P. Bioorg. Med. Chem. Lett.
2009, 19, 4647ꢀ4651. (f) Taylor, A. P.; Robinson, R. P.; Fobian, Y. M.; Blakemore, D. C.; Jones,
L. H.; Fadey, P. Org. Biomol. Chem. 2016, 14, 6611ꢀ6637. (g) Feng, M.; Tang, B.; Liang, S. H.;
Jiang, X. Curr. Top. Med. Chem. 2016, 16, 1200ꢀ1216.
1
2
3
4
5
6
7
8
9
10
11
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17
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51
52
53
54
55
56
57
58
59
60
3. For selected recent articles of the synthesis of sulfones and sulfonamides using sulfinates, see: (a)
Zhang, W.; Luo, M. Chem. Commun., 2016, 52, 2980ꢀ2983. (b) Shavnya, A.; Coffey, S. B.; Hesp,
K. D.; Ross, S. C.; Tsai, A. S. Org. Lett. 2016, 18, 5848ꢀ5851. (c) Gauthier, Jr., D. R.; Yoshikawa,
N. Org. Lett. 2016, 18, 5994ꢀ5997.
4. For selected recent articles on the synthesis of sulfones and sulfonamides from DABSO, see: (a)
Nguyen, B.; Emmett, E. J.; Willis, M. C. J. Am. Chem. Soc. 2010, 132, 16372ꢀ16373. (b) Lenstra,
D. C.; Vedovato, V.; Flegeau, E. F.; Maydom, J.; Willis, M. C. Org. Lett. 2016, 18, 2086ꢀ2089. (c)
Deeming, A. S.; Russell, C. J.; Willis, M. C. Angew. Chem. Int. Ed. 2016, 55, 747ꢀ750.
5. For selected articles on the generation and reactions of metalꢀorganosulfinates, see: (a) Pelzer, G.;
Keim, W. J. Mol. Catal. A: Chem. 1999, 139, 235ꢀ238. (b) Römbke, P.; Schier, A.; Schmidbaur,
H. J. Chem. Soc., Dalton Trans., 2001, 2482ꢀ2486. (c) Shavnya, A.; Coffey, S. B.; Smith, A. C.;
Mascitti, V. Org. Lett. 2013, 15, 6226ꢀ6229. (d) Johnson, M. W.; Bagley, S. W.; Mankad, N. P.;
Bergman, R. G.; Mascitti, V.; Toste, F. D. Angew. Chem. Int. Ed. 2014, 53, 4404ꢀ4407. (e)
Klementyeva, S. V.; Gamer, M. T.; Schmidt, A.ꢀC.; Meyer, K.; Konchenko, S. N.; Roesky, P. W.
Chem. Eur. J. 2014, 20, 13497ꢀ13500. (f) Shavnya, A.; Hesp, K. D.; Mascitti, V.; Smith, A. C.
Angew. Chem. Int. Ed. 2015, 54, 13571ꢀ13575.
6. Metal sulfinates are synthesized by the reaction of organometallic reagents and SO2. (a) Umierski,
N.; Manolikakes, G. Org. Lett. 2013, 15, 4972ꢀ4975. (b) Umierski, N.; Manolikakes, G. J. Org.
Chem. 2015, 80, 2582ꢀ2600.
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7. For selected recent articles on the synthesis of sulfones using various sulfonylating agents, see: (a)
Liu, J.; Zhuang, S.; Gui, Q.; Chen. X.; Yang, Z.; Tan, Z. Eur. J. Org. Chem. 2014, 3196ꢀ3202. (b)
Li, X.; Xu, X.; Hu, P.; Xiao, X.; Zhou, C. J. Org. Chem. 2013, 78, 7343ꢀ7348. (c) Tian, Q.; He, P.;
Kuang, C. Org. Biomol. Chem. 2014, 12, 6349ꢀ6353. (d) Shen, T.; Yuan, Y.; Song, S.; Jiao, N.
Chem. Commun. 2014, 50, 4115ꢀ4118. (e) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H.
Green Chem. 2014, 16, 2988ꢀ2991. (f) Zhang, M.ꢀZ.; Ji, P.ꢀY.; Liu, Y.ꢀF.; Xu, J.ꢀW.; Guo, C.ꢀC.
Adv. Synth. Catal. 2016, 358, 2976ꢀ2983. (g) Ji, P.ꢀY.; Zhang, M.ꢀZ.; Xu, J.ꢀW.; Liu, Y.ꢀF.; Guo,
C.ꢀC. J. Org. Chem. 2016, 81, 5181ꢀ5189.
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8. (a) Hogg D. R., In Comprehensive Organic Chemistry, D. H. R. Barton and W. D. Ollia Eds.; Vol.
3; Pergamon Press, 1979. (b) Barton, D. H. R.; Lacher, B.; Misterkiewicz, B.; Zard, S. Z.
Tetrahedron, 1988, 44, 1153ꢀ1158.
9. (a) Wang, X.; Ji, M.; Lim, S.; Jang, H.ꢀY. J. Org. Chem. 2014, 79, 7256ꢀ7260. (b) Lim, S.; Ji, M.;
Wang, X.; Lee, C.; Jang, H.ꢀY. Eur. J. Org. Chem. 2015, 591ꢀ595. (c) Lee, C.; Lim, Y. N.; Jang,
H.ꢀY. Eur. J. Org. Chem. 2015, 5934ꢀ5938. (d) Lee, C.; Wang, X.; Jang, H.ꢀY. Org. Lett. 2015,
17, 1130ꢀ1133. (e) Shyam, P. K.; Kim, Y. K.; Lee, C.; Jang, H.ꢀY. Adv. Synth. Catal. 2016, 358,
56ꢀ61.
10. For the selected articles regarding the synthesis of thiosulfonates, see: (a) Takata, T.; Kim, Y. H.;
Oae, S. Bull. Chem. Soc. Jpn., 1981, 54, 1143ꢀ1147. (b) Billard, T.; Langlois, B. R.; Large, S.;
Anker, D.; Roidot, N.; Roure, P. J. Org. Chem. 1996, 61, 7545ꢀ7550. (c) Uranpoor, N.; Mohajer,
D.; Rezaeifard, A.ꢀR. Tetrahedron Lett. 2004, 45, 3811ꢀ3815. (d) Mampuys, P.; Zhu, Y.; Vlaar, T.;
Ruijter, E.; Orru, R. V. A.; Maes, B. U. W. Angew. Chem. Int. Ed. 2014, 53, 12849ꢀ12854.
11. Felton, G. A. N.; Bauld, N. L. Tetrahedron Lett. 2004, 45, 4841ꢀ4845.
12. (a) Pospíšil, J.; Sato, H. J. Org. Chem. 2011, 76, 2269ꢀ2272. (b) Markitanov, Y. M.; Timoshenko,
V. M.; Shermolovich, Y. G. J. Sulfur Chem. 2014, 35, 188ꢀ236.
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13. (a) Zhong, Y.ꢀL.; Zhou, H.; Gauthier, Jr., D. R.; Lee, J.; Askin, D.; Dolling, U. H.; Volante, R. P.
Tetrahedron Lett. 2005, 46, 1099ꢀ1101. (b) Hendrick, C. E.; McDonald, S. L.; Wang, Q. Org. Lett.
2013, 15, 3444ꢀ3447.
1
2
3
4
5
6
7
8
9
14. For the synthesis of sulfonamides using thiols and amines, see: (a) Taniguchi, N. Synlett 2007,
1917ꢀ1920. (b) Taniguchi, N. Eur. J. Org. Chem. 2010, 2670ꢀ2673. (c) Sakagami, K.; Jin, X.;
Suzuki, K.; Yamaguchi, K.; Mizuno, N. Chem. Lett. 2016, 45, 173ꢀ175.
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15. Doherty, S.; Knight, J. G.; Carroll, M. A.; Ellison, J. R.; Hobson, S. J.; Stevens, S.; Hardacre, C.;
Goodrich, P. Green Chem. 2015, 17, 1559ꢀ1571.
16. Orita, A.; Ye, F.; Babu, G.; Ikemoto, T.; Otera, J. Can. J. Chem. 2005, 83, 716ꢀ720.
17. Zheng, B.; Jia, T.; Walsh, P. J. Org. Lett. 2013, 15, 1690ꢀ1693.
18. Babu, G.; Orita, A.; Otera, J. Org. Lett. 2005, 7, 4641ꢀ4644.
19. Shukla, P.; Hsu, Y. ꢀC.; Cheng. C. ꢀH. J. Org. Chem. 2006, 71, 655ꢀ658.
20. (a) Kirihara, M.; Yamamoto, J.; Noguchi, T.; Itou, A.; Naito, S.; Hirai, Y. Tetrahedron 2009, 65,
10477ꢀ10484. (b) Mauleón, P.; Alonso, I.; Rivero, M. R.; Carretero, J. J. Org. Chem. 2007, 72,
9924ꢀ9935. (c) Sheng, S. ꢀR.; Zhou, W.; Zhong, M. ꢀH.; Liu, X. ꢀL.; Chen, H. ꢀZ. Synth. Commun.
2005, 35, 815ꢀ821.
21. Rong, G.; Mao, J.; Yan, H.; Zheng, Y.; Zhang, G. J. Org. Chem. 2015, 80, 7652ꢀ7657.
22. Padmanabhan, S.; Ogawa, T.; Suzuki, H. Bull. Chem. Soc. Jpn. 1989, 62, 1358ꢀ1360.
23. Lu, Q.; Zhang, J.; Zhao, G.; Qi, Y.; Wang, H.; Lei, A. J. Am. Chem. Soc. 2013, 135, 11481ꢀ11484.
24. Pandya, V. G.; Mhaske, S. B. Org. Lett. 2014, 16, 3836ꢀ3839.
25. Deeming, A. S.; Russell. C. J.; Hennessy, A. J.; Willis, M. C. Org. Lett. 2014, 16, 150ꢀ153.
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26. Zhao, J. ꢀL.; Guo, S. ꢀH.; Qiu, J.; Gou, X. ꢀF.; Hua, C. ꢀW.; Chen, B. Tetrahedron Lett. 2016, 57,
1
2
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2375ꢀ2378.
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27. Zhu, H.; Shen, Y.; Deng, Q.; Tu, T. Chem. Commun. 2015, 51, 16573ꢀ16576.
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28. Wei, W.; Liu, C. ꢀL.; Yang, D.; Wen, J.; You, J. Adv. Synth. Catal. 2015, 357, 987ꢀ992.
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Graphical Abstract
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No SO2 for sulfinate anion formation
5
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O
O
R S
O
O
Cs2CO3
EtOH
O
O
O
S
R S
O
S
Aryl
NR2
R
SR
arylsulfonamides
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Cu catalyst
O2
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O
O
O
O
O
S
O
R
RSH
S
S
Ph
Alkyl
Ph
Allyl
O
Aryl
O
O
O
O
O
S
O
S
Alkyl
R''
S
Ph
Aryl
Alkyl
R'
aromatic & aliphatic sulfones
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