Waste-Free Swift Synthesis of Symmetrical and Unsymmetrical Diarylmethyl Thioethers from Diaryl Carbinols

Article abstract of DOI:10.1055/s-0036-1589022

A waste-free and swift protocol to synthesize symmetrical and unsymmetrical diarylmethyl thioethers from diaryl carbinols and thiols in good to quantitative yields is reported. The thiol scope included alkyl and aryl thiols bearing electron-donating and electron-withdrawing groups. Short reaction time, high atom economy, inexpensive activator, free from workup and aryl halides, and gram-scale synthesis are the significant features of the new protocol.

Full text of DOI:10.1055/s-0036-1589022

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
en
P. Singh, R. K. Peddinti
Paper
Synthesis
Waste-Free Swift Synthesis of Symmetrical and Unsymmetrical
Diarylmethyl Thioethers from Diaryl Carbinols
Pallavi Singh
R1
R1
Rama Krishna Peddinti*
R1 = R2, Symmetrical
R1 = R2, Unsymmetrical
Indian Institute of Technology Roorkee, Roorkee 247667,
Uttarakhand, India
rkpedfcy@iitr.ac.in
BF3•OEt2
<1 min
R2
R2
ramakpeddinti@gmail.com
S
HO
• Swift synthesis
• Room temperature
• No workup
• No use of aryl halides
• High atom economy
+
R
• Waste-free reaction
• 48 Examples
• Up to >99% yield
• Large-scale
SH
R
R = Aryl, Alkyl
Received: 31.01.2017
Accepted after revision: 07.04.2017
Published online: 29.05.2017
Novel approaches to break and form carbon–heteroat-
om bonds provide opportunities to develop new protocols
and to expand the chemist’s synthetic repertoire.11 Exam-
ple applications of thioethers in organic synthesis are illus-
trated in Figure 1. Among the wide-spread category of thio-
ethers, benzhydryl thioethers serve as appropriate probes
in enzymatic and biomimetic oxidation processes to test
the intermediacy of radical cations.12 The metal-catalyzed
arylation of C–H bonds in benzyl thioethers was demon-
strated as an unprecedented approach to synthesize diaryl
sulfides.13 Recently, synthetic chemists have employed sta-
ble aryl diphenylmethyl sulfides for the investigation of
electron-transfer–oxygen-transfer mechanism.14 Olah and
co-workers reported the formation of C–F bonds through
the oxidative desulfurative fluorination of phenyl sulfides.15
DOI: 10.1055/s-0036-1589022; Art ID: ss-2017-z0061-op
Abstract A waste-free and swift protocol to synthesize symmetrical
and unsymmetrical diarylmethyl thioethers from diaryl carbinols and
thiols in good to quantitative yields is reported. The thiol scope includ-
ed alkyl and aryl thiols bearing electron-donating and electron-with-
drawing groups. Short reaction time, high atom economy, inexpensive
activator, free from workup and aryl halides, and gram-scale synthesis
are the significant features of the new protocol.
Key words thioetherification, diarylmethyl thioethers, diaryl, carbi-
nols, high atom economy, Lewis acid activator
Part of the renaissance in C–heteroatom bond forma-
tion, the C–S bond has enjoyed a special status and focus on
its activation.1 Highly selective functionalization of the C–S
bond can accurately modify sulfur-containing molecules.2
Organosulfur compounds are in great demand as interme-
diates for the synthesis of bioactive natural products and
often possess therapeutic activities.3 Sulfides are particu-
larly attractive sources of carbon centered radicals due to
their reactivity and stability.4 The biaryl sulfides are im-
portant structural motifs for several drugs, which are used
against Alzheimer’s, Parkinson’s, malarial, inflammatory,
HIV, and cancer diseases.5 Among the sulfur-derived func-
tional groups, thioethers6 (e.g., cephalosporin analogues),
their derived sulfoxides7 (e.g., armodafinil, omeprazole, and
ajoene) and sulfones8 (e.g., dapsone) have been effectively
used in research areas of medicinal chemistry and human
health care.6–8 Bunch of thioethers and sulfones are being
harnessed as synthons for the synthesis of novel products
for human needs and more valuable materials.9 Along these
lines, modern synthetic chemists have efficiently used thio-
ethers as prominent organocatalysts and good ligands in
transition-metal catalysis.10
Probes in enzymatic and biomimetic oxidations
1
S
4
2
C–F bond
formation
Aryl sulfides
synthesis
R
3
Electron-transfer–oxygen-transfer mechanism
Figure 1 Applications of diarylmethyl thioethers
To date, several methods for synthesizing thioethers,
mainly involving catalytic strategies, have proven success-
ful.16 Despite the exploration of numerous transformations
for making C–S bonds, these methods have considerable
limitations in important areas of research because sulfur
easily undergoes oxidative formation of the undesired S–S
bond, leading to disulfide by-products.17 Sulfur has strong
coordinating ability with metals, which deactivates the
metal catalysts when compared to C–N and C–O bond for-
mation.18 A couple of reports demonstrated that diaryl-
methyl thioethers have also been prepared by using protic
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

B
P. Singh, R. K. Peddinti
Paper
Synthesis
ionic liquids19 and silica-supported perchloric acid20 but
these methods suffer from limitation of toxicity and harsh
reaction conditions, are expensive, and require additional
steps for the synthesis of the catalyst. Over several years,
much of the work has been devoted to thioether synthesis
through the cross-coupling of thiols with aryl halides
where transition metals such as nickel,21 cobalt,22 palladi-
um,23 and iron24 have been found as excellent catalysts for
this purpose. Copper and copper-based enzyme laccase are
better at catalyzing the reactions in most cases.25 The N-
chlorosuccinimide was implemented by Lee and co-work-
ers in a remarkable synthesis of aryl sulfides via thioetheri-
fication reaction of thiols and corresponding Grignard re-
agents with suitable metals.26 Considerable limitations of
these methods in the cross-coupling of thiols with aryl ha-
lides have shown serious issues to synthetic chemists. A
drawback of Pd, Cu, Co, and Ni catalysts is the requirement
for long reaction time, high reaction temperature, low sen-
sitivity, tedious workup procedures, and their associated
toxicity, which may limit the wide application of these cat-
alysts. To this need, the judicious design of new methods in-
volving less energy, inexpensive precursors, and the use of
cheap, eco-friendly, and easily available catalysts are highly
desirable in this area of research.
our preliminary studies, the reaction proceeded smoothly
under the influence of triflic acid and the product was ob-
tained in good yield (70%) (Table 1, entry 1). Further, we
moved for the optimization of reaction conditions. Interest-
ingly, it was found that 20 mol% of Brønsted acids p-
TSA·H2O and trifluoroacetic acid worked effectively to fur-
nish 3aa in enhanced yield of 75–78% (entries 2 and 3). On
screening with Lewis acids such as SnCl4, FeCl3, and ZrCl4,
the reaction was found to be complete within minutes and
good amount (82–87%) of product was isolated (entries 4–
6).
Table 1 Optimization of Reaction Conditionsa
SH
1a
acid activator
CH2Cl2, r.t.
S
+
OH
3aa
2a
Entry
Activator (mol%)
Time (min)
Yield (%)b
The electron acceptor boron trifluoride has been receiv-
ing more and more attention due to its strong Lewis acid
character. Among the Lewis acids, BF3·OEt2 is a very reactive
adduct of BF3 and Et2O through sigma-bonding.27 In recent
years, BF3·OEt2 based activation has provided a powerful av-
enue in modern organic synthesis where it is employed in
alkylation, cyclization, rearrangement, Michael addition,
and coupling reactions.28 Interest in BF3·OEt2-catalyzed
transformations has blossomed because of its eco-friendly
nature, efficient reactivity, and low cost. Although several
diverse approaches have been reported for the synthesis of
diarylmethyl thioethers, the development of sustainable
and practical synthetic protocol is still an attractive goal for
synthetic practitioner. In this context, with the advent of
advancement in diaryl carbinols chemistry,29 we herein re-
port a waste-free, direct, and swift synthesis of symmetri-
cal diarylmethyl thioethers (SDAMTs) and unsymmetrical
diarylmethyl thioethers (unSDAMTs) by using simple and
easily available BF3·OEt2 via dehydrative SN1 reaction.
Given the importance to benzhydryl alcohols, which can
be activated under mild conditions using Lewis acids or
Brønsted acids and liberate water as by-product,30 we em-
barked our study with the synthesis of diaryl carbinols with
the known procedure.31 Identifying the suitable activator
for the synthesis of symmetrical and unsymmetrical diaryl-
methyl thioethers is an important task. For this purpose,
benzyl mercaptan (1a) and di-(p-tolyl)methanol (2a) were
selected in the presence of various acid activators in di-
chloromethane at room temperature as a model system. In
1
2
TfOH (20)
p-TSA·H2O (20)
TFA (20)
100
60
60
20
20
20
10
<1
<1
<1
70
75
3
78
4
SnCl4 (20)
FeCl3 (20)
ZrCl4 (20)
82
5
87
6
87
7
I2 (20)
75
8
BF3·OEt2 (20)
BF3·OEt2 (10)
BF3·OEt2 (5)
>99
>99
>99
9
10
a Reactions of 1a (0.5 mmol) with 2a (0.6 mmol) in the presence of various
activator were carried out in 2 mL of CH2Cl2.
b Yield of pure and isolated products.
Surprisingly molecular iodine enhanced the rate of re-
action albeit with diminished yield of the product as 1a
readily undergoes oxidative S–S bond formation (Table 1,
entry 7). During the screening process, 20 mol% of BF3·OEt2
pleasantly furnished the thioether 3aa in quantitative yield
within seconds (entry 8). Then the model reaction was ex-
amined to check the impact of the quantity of BF3·OEt2 on
the reaction yield and time. Decreasing the loading of
BF3·OEt2 from 20 mol% to 5 mol% had no obvious effect on
yield and rate of the reaction (entries 9 and 10). This
screening led to the identification that BF3·OEt2 affords the
product 3aa without any impurities or side products within
seconds.
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C
P. Singh, R. K. Peddinti
Paper
Synthesis
Once the optimal conditions were established with the
identification of suitable activator for the facile synthesis of
diarylmethyl thioether, the scope of this swift protocol was
probed to a range of aliphatic and aromatic thiols with di-
aryl carbinols (Scheme 1). Thus the reaction of 1a with di-
phenyl carbinol (2b) and other alcohols 2c and 2d, bearing
electron-withdrawing halo groups, furnished thioethers
3ab, 3ac, and 3ad in quantitative yield. Further, the reactiv-
ity of cyclohexanethiol (1b) was examined with 2a–d for
this transformation, which yielded the products 3ba, 3bb,
3bc, and 3bd in excellent yields (90–98%).
When parent thiophenol was employed in the reaction
with alcohols 2a–d, the products 3ca, 3cb, 3cc, and 3cd
were obtained in 85–96% yield. To extend the substrate
scope of the developed protocol we used 4-methoxythio-
phenol (1d) and 4-methylthiophenol (1e) as nucleophiles
in combination with diarylcarbinols 2a–d. Delightedly, the
OH
BF3•OEt2
(5 mol%)
S
R
S
H
R
+
CH2Cl2
r.t., <1 min
R = alkyl, aryl
2a–d
1a–h
3
F
Cl
H
H
H
H
S
H
H
S
H
S
S
S
S
H
3aa, >99%
3ab, >99%
3ac, >99%
3bb, 95%
3ba, 98%
3ad, >99%
F
Cl
Cl
F
Cl
F
S
S
S
S
S
S
3cb, 90%
3cd, 85%
3bc, 93%
3ca, 96%
3bd, 90%
3cc, 87%
Cl
F
Cl
F
Cl
F
S
MeO
S
MeO
S
MeO
S
MeO
S
3da, 99%
3dc, 96%
3db, 99%
3dd, 95%
3eb, 96%
Cl
F
F
Cl
F
Br
S
Br
S
Br
S
S
S
3fb, 87%
3fc, 83%
3fa, 90%
3ed, 95%
3ec, 95%
F
Cl
Cl
F
F
F
O
S
Br
S
MeO
S
F
F
Cl
3gc, 90%
3hc, >99%
3fd, 80%
Scheme 1 Scope for waste-free synthesis of symmetrical diarylmethyl thioethers. Reagents and conditions: Thiol 1 (0.5 mmol), diarylcarbinol 2 (0.6
mmol), BF3·OEt2 (5 mol%), CH2Cl2 (2 mL).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

D
P. Singh, R. K. Peddinti
Paper
Synthesis
SDAMTs 3da–dd and 3eb–ed were isolated in excellent to
quantitative yields. Encouraged by these results, thiol 1f
bearing electron-withdrawing bromo group at 4-position
was investigated for this expeditious protocol and the cor-
responding SDAMT products 3fa–fd were achieved in high
yields. Thiols such as o-thiocresol (1g) and methyl mercap-
topropionate (1h) worked well with bis(4-fluorophe-
nyl)methanol (2c) under optimized conditions to produce
the thioethers 3gc and 3hc in excellent yield.
With the promising results in hand, we next extended
the current protocol to synthesize unSDAMTs. This protocol
shows the generality of diaryl carbinols 2e–g having phenyl
and monosubstituted phenyl groups with various alkyl and
aryl thiols (Scheme 2). Variation of halo groups at 4-posi-
tion of monosubstituted diaryl secondary alcohols was
found to be tolerable with benzenemethanethiol (1a) and
resulted in the products 4ae–ag in quantitative yield. When
cyclohexanethiol was submitted for unSDAMT products un-
der our standard conditions, the diarylcarbinols 2e–g re-
sulted in the formation of thioethers 4be–bf in very good to
excellent yields (89–97%).
4ee, and 4ef in good to excellent yields ranging from 85–
98%. 4-Bromothiophenol (1f) was also easily provided the
thioethers 4fe–fg in very good yields within seconds.
Afterwards, diaryl carbinols bearing ortho- and meta-
substituted phenyl groups and even a 2,4-disubstituted
phenyl group were employed as substrates to examine the
feasibility of this methodology (Figure 2). Benzyl mercap-
tan (1a) was found to be ideal reaction partner with 2h and
2i affording the products 5ah and 5ai in quantitative yields.
When methyl mercaptopropionate was subjected to this
protocol, the products 5hi and 5hj were obtained in excel-
lent to quantitative yields. In addition to alkyl thiols, when
o-thiocresol (1g) was the choice of substrate in this swift
protocol, the unsymmetrical thioether 5gh was isolated in
91% yield. 4-Nitrothiophenol was also found to be an ideal
precursor for this transformation, giving rise to 5ii in 83%
yield.
Inspired by above results and environmentally benign
approach, the present method was evaluated for the gram-
scale synthesis. The reaction between 1a and 2b was then
conducted at 10 mmol level, which furnished benzhy-
dryl(benzyl)sulfane (3ab) in quite a good amount (2.6 g;
90%) (Scheme 3). This confirmed the utility of elegant pro-
tocol in the gram-scale preparation of diarylmethyl thio-
ethers.
The importance of waste-free protocol was further ex-
plored by employing the parent thiophenol (1c) and elec-
tron-rich thiols 1d and 1e with 2e–g under aforementioned
conditions, which afforded unSDMATs, 4ce–cg, 4de–dg,
BF3•OEt2
(5 mol%)
OH
S
H
S
R
+
R
CH2Cl2
r.t., <1 min
4
1a–f
R = alkyl, aryl
Cl
2e–g
Cl
F
Br
Br
F
H
H
H
H
H
S
S
S
S
S
S
H
4ag, >99%
Br
4ae, >99%
4af, >99%
Cl
4be, 97%
4bf, 93%
4bg, 89%
F
Cl
Br
F
S
S
MeO
S
S
MeO
S
MeO
S
4ce, 91%
4cf, 87%
4cg, 82%
4de, 97%
4df, 95%
4dg, 87%
Br
F
Cl
F
Cl
Br
S
Br
S
Br
S
S
S
4ee, 96%
4ef, 95%
4fe, 87%
4ff, 83%
4fg, 73%
Scheme 2 Scope for waste-free synthesis of unsymmetrical diarylmethyl thioethers. Reagents and conditions: Thiol 1 (0.5 mmol), diaryl carbinol 2 (0.6
mmol), BF3·OEt2 (5 mol%), CH2Cl2 (2 mL).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

E
P. Singh, R. K. Peddinti
Paper
Synthesis
OH
BF3•OEt2
(5 mol%)
S
SH
+
CH2Cl2
r.t., 10 min
1a (10 mmol)
2b (12 mmol)
3ab 90% (2.6 g)
Scheme 3 Gram-scale synthesis of thioether 3ab
of inexpensive BF3·OEt2 as a catalyst and easily available
precursors. The level of success in the swift reaction is
somewhat dependent on the thiophenol nucleophilicity
and the substituents on benzhydryl alcohols. It was also ob-
served that bromo substitution on the thiol decreased the
yield in the reaction. Nevertheless, the direct thiophenol-
into-thioether conversion constitutes a powerful track for
the high-yielding synthesis of diarylmethyl thioethers.
Metal-free conditions, broad substrate scope with diverse
substitution patterns, large-scale preparation, and opera-
tional simplicity are noteworthy features of this economic
synthetic process.
H
H
H
H
O
S
S
MeO
S
Cl
Cl
Cl
5ah, >99%
5ai, >99%
5hi, >99%
O
S
S
O2N
MeO
S
Cl
Cl
Cl
Cl
5gh, 91%
5hj, >99%
5ii, 83%
Figure 2 Scope for waste-free synthesis of unsymmetrical diarylmeth-
yl thioethers. Reaction conditions: Thiol 1 (0.5 mmol), diaryl carbinol 2
(0.6 mmol), BF3·OEt2 (5 mol%), CH2Cl2 (2 mL), <1 min (cf. Schemes 1
and 2).
All obtained symmetrical and unsymmetrical diarylmethyl thioethers
were fully characterized. Synthesis of all diarylmethyl thioethers
were carried out at r.t. Commercially available chemicals were pur-
chased from commercial vendors in highest purity grade and used di-
rectly for waste-free protocol without further purification. All syn-
theses were performed in standard glassware without any special
precautions taken for the removal of moisture or air. CH2Cl2 was puri-
fied by distillation over the P2O5. Merck precoated 0.25 mm silica gel
plates (60F-254) were used to perform the analytical TLC. Visualiza-
tion was achieved with short wave UV light. Eluting solvents are
mentioned in the general procedure for synthesis. Column chroma-
tography was carried out with silica gel (100–200 mesh) using EtOAc/
hexanes. 1H (400 MHz) and 13C NMR (100 MHz) spectra were record-
ed on Jeol spectrometer, respectively. Chemical shift in 1H NMR is ref-
erenced internally to residual solvent peak (δ = 7.26) as internal stan-
dard in SiMe4 (δ = 0.00) ppm. 13C NMR spectra were referenced to CD-
Cl3 (δ = 77.0, the middle peak). Chemical shifts (δ) are reported as
ppm in δ scale downfield from TMS. Coupling constants are ex-
pressed in Hz. The multiplicity was explained by standard abbrevia-
tions. Melting points were recorded on a Perfit melting point instru-
ment and are uncorrected.
As the present methodology holds the advantage of easy
operation, nontoxic, allows the use of readily available and
inexpensive catalyst as well as direct use of diaryl carbinols,
free from workup and waste release, and water is the only
by-product, this is a more attractive method than the re-
ported methods. Therefore, to the best of our knowledge,
this is the first ever report on thiolation of diaryl carbinols
that use BF3·OEt2 as a catalyst to accomplish the merging of
diaryl carbinols with thiols.
Based on the above experimental results and related lit-
erature reports32 these reactions presumably proceed via
dehydrative SN1 mechanism (Scheme 4). A benzyl carbo-
cation 6 might be formed from diaryl carbinol 2 in the pres-
ence of BF3·OEt2 and then 6 could be attacked by thiol 1 to
afford the product diarylmethyl thioether.
Symmetrical and Unsymmetrical Diarylmethyl Thioethers; Gener-
al Procedure
Ar1
Ar2
Ar1
Ar1
Ar2
..
BF3•OEt2
r.t.
To a solution of thiol 1 (0.5 mmol) in anhyd CH2Cl2 (2 mL) was added
diaryl carbinol 2 (0.6 mmol) and BF3·OEt2 (5 mol% solution in CH2Cl2;
1 mL). The reaction mixture was stirred vigorously for <1 min. After
completion of the reaction as checked by TLC, the solvent was re-
moved under reduced pressure, and the residue was subjected to sili-
ca gel column chromatography by using 5–10% EtOAc in hexanes to
afford the desired symmetrical and unsymmetrical diarylmethyl thio-
ether in good to quantitative yield.
.
O
BF3•OEt2
H2O
+
S
R
+
Ar2
..
H
H
R
S
..
1
6
2
diaryl methyl
thioethers
Scheme 4 Plausible reaction mechanism
In summary, we have reported a novel, waste-free, and
swift synthesis of symmetrical and unsymmetrical diaryl-
methyl thioethers with high atom economy. The developed
methodology is highly efficient and practical due to the use
Benzyl[di(p-tolyl)methyl]sulfane (3aa)
Yield: 157 mg (>99%); yellow liquid.
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F
P. Singh, R. K. Peddinti
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.34–7.24 (m, 9 H), 7.14–7.12 (m, 4 H),
4.93 (s, 1 H), 3.57 (s, 2 H), 2.34 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 138.38, 138.29, 136.85, 129.39,
129.17, 128.54, 128.45, 127.02, 52.79, 36.72, 21.20.
1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 8.0 Hz, 3 H), 7.31 (t, J = 7.6
Hz, 3 H), 7.24–7.20 (m, 2 H), 5.26 (s, 1 H), 2.53–2.46 (m, 1 H), 1.95–
1.91 (m, 2 H), 1.75–1.72 (m, 2 H), 1.57–1.54 (m, 1 H), 1.44–1.35 (m, 2
H), 1.29–1.15 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 142.09, 128.62, 128.40, 127.10, 52.56,
43.66, 33.37, 25.99, 25.92.
Benzhydryl(benzyl)sulfane (3ab)
Yield: 134 mg (>99%); white solid; mp 72–74 °C.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.43 (m, 5 H), 7.35–7.33 (m, 6 H),
7.3–7.26 (m, 4 H), 5.00 (s, 1 H), 3.60 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 142.12, 138.08, 129.17, 128.71,
[Di-(p-tolyl)methyl](phenyl)sulfane (3ca)
Yield: 146 mg (96%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 8.0 Hz, 4 H), 7.25–7.23 (m, 2
H), 7.20–7.09 (m, 7 H), 5.51 (s, 1 H), 2.31 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 138.31, 136.91, 136.69, 130.14,
128.60, 127.32, 127.12, 53.30, 36.17.
129.33, 128.78, 128.30, 126.37, 56.76, 21.17.
Benzyl[bis(4-fluorophenyl)methyl]sulfane (3ac)
Yield: 155 mg (>99%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.26 (m, 9 H), 7.08–7.03 (m, 4 H),
4.98 (s, 1 H), 3.60 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 162.0 (d, J = 245.0 Hz, CF), 137.79,
136.75, 136.72, 130.19, 130.11, 129.05, 128.64, 127.27, 115.62 (d, J =
29.4 Hz), 51.73, 36.52.
Benzhydryl(phenyl)sulfane (3cb)
Yield: 124 mg (90%); white solid; mp 67–68 °C (Lit.33 mp 66–68 °C).
1H NMR (400 MHz, CDCl3): δ = 7.41–7.39 (m, 4 H), 7.30–7.11 (m, 11
H), 5.23 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 141.09, 136.22, 130.60, 128.82,
128.64, 128.51, 127.36, 127.67, 57.52.
Benzyl[bis(4-chlorophenyl)methyl]sulfane (3ad)
[Bis(4-fluorophenyl)methyl](phenyl)sulfane (3cc)
Yield: 178 mg (>99%); yellow liquid.
Yield: 135 mg (87%); white solid; mp 68–70 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.36 (m, 4 H), 7.24–7.18 (m, 5 H),
7.01 (t, J = 8.8 Hz, 4 H), 5.53 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 162.03 (d, J = 245.0 Hz, CF), 136.70,
136.65, 135.50, 131.02, 130.09, 130.0, 128.96, 127.09, 115.58 (d, J =
29.5 Hz), 56.13.
1H NMR (400 MHz, CDCl3): δ = 7.31–7.24 (m, 11 H), 7.19–7.17 (m, 2
H), 4.83 (s, 1 H), 3.54 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 139.16, 137.54, 133.25, 129.84,
129.05, 128.91, 128.63, 127.30, 57.80, 36.69.
Cyclohexyl[di(p-tolyl)methyl]sulfane (3ba)
Yield: 152 mg (98%); yellow liquid.
[Bis(4-chlorophenyl)methyl](phenyl)sulfane (3cd)
Yield: 146 mg (85%); white solid; mp 72–74 °C.
1H NMR (400 MHz, CDCl3): δ = 7.33–7.17 (m, 13 H), 5.47 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.19, 135.22, 133.38, 131.08,
129.81, 129.05, 128.91, 127.25, 56.37.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.41 (m, 4 H), 7.21–7.19 (m, 4 H),
5.31 (s, 1 H), 2.63–2.56 (m, 1 H), 2.40 (s, 6 H), 2.40–2.00 (m, 2 H),
1.82–1.80 (m, 2 H), 1.64–1.59 (m, 1 H), 1.54–1.45 (m, 2 H), 1.36–1.27
(m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 139.42, 136.60, 129.36, 128.30, 52.0,
43.62, 33.46, 26.13, 25.98, 21.26.
[Di(p-tolyl)methyl](4-methoxyphenyl)sulfane (3da)
Benzhydryl(cyclohexyl)sulfane (3bb)
Yield: 165 mg (99%); yellow liquid.
Yield: 134 mg (95%); white solid; mp 64–66 °C.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.29 (m, 4 H), 7.25–7.23 (m, 2 H),
7.12 (d, J = 11.2 Hz, 4 H), 6.75 (d, J = 8.8 Hz, 2 H), 5.35 (s, 1 H), 3.76 (s,
3 H), 2.33 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 159.24, 138.65, 136.76, 134.36,
129.25, 128.32, 126.51, 114.37, 58.72, 55.37, 21.18.
1H NMR (400 MHz, CDCl3): δ = 7.42–7.40 (m, 4 H), 7.30–7.26 (m, 4 H),
7.22–7.17 (m, 2 H), 5.22 (s, 1 H), 2.50–2.43 (m, 1 H), 1.90–1.87 (m, 2
H), 1.71–1.68 (m, 2 H), 1.54–1.51 (m, 1 H), 1.40–1.32 (m, 2 H), 1.25–
1.22 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 142.07, 128.60, 128.38, 127.08, 52.49,
43.65, 33.35, 25.97, 25.90.
Benzhydryl(4-methoxyphenyl)sulfane (3db)
Yield: 151 mg (99%); white solid; mp 89–90 °C.
1H NMR (400 MHz, CDCl3): δ = 7.47–7.45 (m, 4 H), 7.36–7.26 (m, 8 H),
6.79 (d, J = 8.4 Hz, 2 H), 5.42 (s, 1 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.41, 141.39, 134.83, 128.29,
128.10, 127.42, 125.83, 114.38, 65.63, 55.25.
[Bis(4-fluorophenyl)methyl](cylohexyl)sulfane (3bc)
Yield: 148 mg (93%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.36 (m, 4 H), 7.00 (t, J = 8.8 Hz, 4
H), 5.22 (s, 1 H), 2.49–2.42 (m, 1 H), 1.91–1.87 (m, 2 H), 1.73–1.71 (m,
2 H), 1.56–1.54 (m, 1 H), 1.42–1.33 (m, 2 H), 1.24–1.15 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.88 (d, J = 244.7 Hz, CF), 137.65,
129.87, 129.78, 115.50 (d, J = 21.9 Hz), 100.0, 50.93, 43.78, 33.28,
25.88.
[Bis(4-fluorophenyl)methyl](4-methoxyphenyl)sulfane (3dc)
Yield: 164 mg (96%); white solid; mp 75–77 °C.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.30 (m, 4 H), 7.19 (d, J = 8.8 Hz, 2
H), 6.98 (t, J = 8.8 Hz, 4 H), 6.74 (d, J = 8.8 Hz, 2 H), 5.32 (s, 1 H), 3.75 (s,
3 H).
[Bis(4-chlorophenyl)methyl](cylohexyl)sulfane (3bd)
Yield: 158 mg (90%); white solid; mp 66–68 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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P. Singh, R. K. Peddinti
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 161.24 (t, J = 245.0 Hz, CF), 137.04,
137.02, 135.14, 130.14, 130.07, 125.36, 115.61, 115.50 (d, J = 21.0 Hz),
114.56, 57.95, 55.41.
[Bis(4-chlorophenyl)methyl](4-bromophenyl)sulfane (3fd)
Yield: 170 mg (80%); white solid; mp 82–85 °C.
1H NMR (400 MHz, CDCl3): δ = 7.30–7.20 (m, 10 H), 7.05 (d, J = 8.0 Hz,
2 H), 5.40 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.59, 133.19, 132.47, 131.48,
131.01, 128.64, 127.90, 120.30, 55.28.
[Bis(4-chlorophenyl)methyl](4-methoxyphenyl)sulfane (3dd)
Yield: 177 mg (95%); white solid; mp 68–70 °C.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.21 (m, 10 H), 6.76 (d, J = 8.4 Hz,
2 H), 5.37 (s, 1 H), 3.75 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.66, 139.41, 135.12, 133.10,
129.77, 128.69, 124.93, 114.45, 58.06, 55.28.
[Bis(4-fluorophenyl)methyl](o-tolyl)sulfane (3gc)
Yield: 141 mg (90%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.35–7.32 (m, 4 H), 7.15–6.96 (m, 8 H),
5.46 (s, 1 H), 3.0 (s, 3 H).
Benzhydryl(p-tolyl)sulfane (3eb)
13C NMR (100 MHz, CDCl3): δ = 163.25, 160.80, 138.33, 136.64,
134.85, 130.26, 130.06, 129.98, 126.71, 126.48, 115.68, 115.46, 54.97,
20.50.
Yield: 139 mg (96%); white solid; mp 60–62 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.16 (m, 10 H), 7.11 (d, J = 8.0 Hz,
2 H), 6.97 (d, J = 8.0 Hz, 2 H), 5.44 (s, 1 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 140.30, 141.29, 136.87, 132.35,
Methyl 3-[Bis(4-fluorophenyl)methyl]thiopropanoate (3hc)
131.40, 129.57, 128.55, 127.24, 58.11, 21.17.
Yield: 160 mg (>99%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.34 (m, 4 H), 7.0 (t, J = 8.4 Hz, 4
H), 5.18 (s, 1 H), 3.68 (s, 3 H), 2.65 (t, J = 7.2 Hz, 2 H), 2.54 (t, J = 6.8 Hz,
2 H).
[Bis(4-fluorophenyl)methyl](p-tolyl)sulfane (3ec)
Yield: 155 mg (95%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.44–7.35 (m, 4 H), 7.22–7.20 (m, 2 H),
13C NMR (100 MHz, CDCl3): δ = 172.30, 163.24, 160.79, 136.74,
7.12–7.04 (m, 6 H), 5.51 (s, 1 H), 2.36 (s, 3 H).
136.71, 129.94, 129.86, 115.75, 115.54, 52.79, 51.96, 34.10, 27.27.
13C NMR (100 MHz, CDCl3): δ = 161.96 (d, J = 245.0 Hz, CF), 137.40,
136.86, 131.81, 131.59, 130.06, 129.97, 129.71, 115.48 (d, J = 21.0 Hz),
56.69, 21.16.
Benzyl[(4-fluorophenyl)(phenyl)methyl]sulfane (4ae)
Yield: 152 mg (>99%); white solid; mp 48–50 °C.
1H NMR (400 MHz, CDCl3): δ =7.41–7.24 (m, 12 H), 7.03 (t, J = 8.8 Hz,
2 H), 4.96 (s, 1 H), 3.59 (s, 2 H).
[Bis(4-chlorophenyl)methyl](p-tolyl)sulfane (3ed)
Yield: 170 mg (95%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.28–7.19 (m, 8 H), 7.10 (d, J = 8.0 Hz, 2
H), 6.98 (d, J = 8.0 Hz, 2 H), 5.36 (s, 1 H), 2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.97 (d, J = 244.0 Hz, CF), 140.92,
137.94, 136.94, 130.23, 129.13, 128.80, 128.62, 128.53, 115.53 (d, J =
22.0 Hz), 52.50, 36.74.
13C NMR (100 MHz, CDCl3): δ = 139.19, 137.38, 133.22, 133.07,
131.71, 131.13, 129.60, 128.62, 56.76, 20.96.
Benzyl[(4-chlorophenyl)(phenyl)methyl]sulfane (4af)
Yield: 161 mg (>99%); yellow liquid.
(4-Bromophenyl)[di(p-tolyl)methyl]sulfane (3fa)
1H NMR (400 MHz, CDCl3): δ = 7.42–7.24 (m, 14 H), 4.96 (s, 1 H), 3.61
Yield: 172 mg (90%); white solid; mp 96–98 °C.
(s, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.26–7.23 (m, 6 H), 7.08–7.03 (m, 6 H),
5.44 (s, 1 H), 2.28 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 137.78, 137.13, 135.77, 131.66,
13C NMR (100 MHz, CDCl3): δ = 140.69, 139.80, 137.90, 133.09,
130.14, 129.24, 128.92, 128.84, 128.66, 128.53, 127.57, 127.29, 52.57,
36.30.
129.42, 129.34, 128.28, 120.36, 56.80, 21.17.
Benzyl[(4-bromophenyl)(phenyl)methyl]sulfane (4ag)
Benzhydryl(4-bromophenyl)sulfane (3fb)
Yield: 183 mg (>99%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ =7.46–7.44 (m, 2 H), 7.37–7.31 (m, 6 H),
Yield: 154 mg (87%); white solid; mp 108–110 °C.
1H NMR (400 MHz, CDCl3): δ = 7.40–7.38 (m, 4 H), 7.30–7.20 (m, 8 H),
7.06 (d, J = 8.4 Hz, 2 H), 5.49 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.58, 135.29, 132.15, 131.87,
7.28–7.22 (m, 6 H), 4.90 (s, 1 H), 3.56 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 140.55, 140.28, 137.82, 131.79,
130.36, 129.13, 128.82, 128.63, 128.50, 127.54, 127.24, 121.19, 52.65,
36.72.
128.72, 128.45, 127.52, 120.72, 57.54.
Cyclohexyl[(4-fluorophenyl)(phenyl)methyl]sulfane (4be)
[Bis(4-fluorophenyl)methyl](4-bromophenyl)sulfane (3fc)
Yield: 145 mg (97%); colorless liquid.
Yield: 162 mg (83%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.35 (m, 4 H), 7.30–7.26 (m, 2 H),
7.22–7.17 (m, 1 H), 6.96 (t, J = 8.8 Hz, 2 H), 5.19 (s, 1 H), 2.46–2.39 (m,
1 H), 1.88–1.85 (m, 2 H), 1.70–1.67 (m, 2 H), 1.53–1.51 (m, 1 H), 1.38–
1.30 (m, 2 H), 1.23–1.11 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.83 (d, J = 244.0 Hz, CF), 141.84,
137.83, 129.94, 129.85, 128.66, 128.26, 127.21, 115.39 (d, J = 21.0 Hz),
51.74, 43.71, 33.33, 25.89.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.26 (m, 6 H), 7.07–6.95 (m, 6 H),
5.47 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 162.12 (d, J = 245.0 Hz, CF), 137.60,
136.27, 134.66, 132.58, 132.07, 130.11, 130.03, 128.85, 121.26,
115.64 (t, J = 21.5 Hz), 79.01, 56.19.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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P. Singh, R. K. Peddinti
Paper
Synthesis
Cyclohexyl[(4-chlorophenyl)(phenyl)methyl]sulfane (4bf)
[(4-Bromophenyl)(phenyl)methyl](4-methoxyphenyl)sulfane
(4dg)
Yield: 147 mg (93%); yellow liquid.
Yield: 167 mg (87%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.41–7.34 (m, 4 H), 7.31–7.19 (m, 7 H),
6.73 (d, J = 8.4 Hz, 2 H), 5.30 (s, 1 H), 3.75 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.58, 140.77, 140.56, 135.0, 131.32,
130.28, 128.67, 128.09, 127.41, 125.46, 121.09, 114.49, 58.78, 55.35.
1H NMR (400 MHz, CDCl3): δ = 7.43–7.39 (m, 4 H),7.34–7.28 (m, 4 H),
7.24–7.17 (m, 1 H), 5.24 (s, 1 H), 2.54–2.46 (m, 1 H), 1.94–1.91 (m, 2
H), 1.76–1.72 (m, 2 H), 1.57–1.55 (m, 1 H), 1.45–1.36 (m, 2 H), 1.28–
1.20 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 141.61, 140.74, 132.83, 129.81,
128.77, 128.72, 128.31, 127.30, 51.90, 43.78, 33.36, 25.96, 25.91.
[(4-Fluorophenyl)(phenyl)methyl](p-tolyl)sulfane (4ee)
Cyclohexyl[(4-bromophenyl)(phenyl)methyl]sulfane (4bg)
Yield: 148 mg (96%); white solid; mp 53–55 °C.
Yield: 161 mg (89%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.40–6.92 (m, 12 H), 5.45 (s, 1 H), 2.27
1H NMR (400 MHz, CDCl3): δ = 7.41–7.36 (m, 4 H),7.30–7.28 (m, 4 H),
7.21–7.18 (m, 1 H), 5.17 (s, 1 H), 2.49–2.42 (m, 1 H), 1.89–1.86 (m, 2
H), 1.70–1.68 (m, 2 H), 1.54–1.52 (m, 1 H), 1.40–1.31 (m, 2 H), 1.24–
1.15 (m, 3 H).
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.94 (d, J = 245.0 Hz, CF), 141.09,
137.18, 132.01, 131.68, 130.18, 130.09, 129.68, 128.67, 128.43,
127.41, 115.40 (d, J = 21.0 Hz), 57.46, 21.15.
13C NMR (100 MHz, CDCl3): δ = 141.61, 140.74, 132.83, 129.81,
128.77, 128.72, 128.31, 127.30, 51.90, 43.78, 33.36, 25.96, 25.91.
[(4-Chlorophenyl)(phenyl)methyl](p-tolyl)sulfane (4ef)
Yield: 154 mg (95%); white solid; mp 68–70 °C.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.19 (m, 9 H), 7.12 (d, J = 8.0 Hz, 2
H), 6.98 (d, J = 8.0 Hz, 2 H), 5.41 (s, 1 H), 2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 140.77, 139.90, 133.0, 131.83, 131.71,
131.64, 129.93, 129.68, 128.74, 128.40, 127.45, 57.52, 21.19.
[(4-Fluorophenyl)(phenyl)methyl](phenyl)sulfane (4ce)
Yield: 134 mg (91%); white solid; mp 71–73 °C.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.28 (m, 4 H), 7.22–7.20 (m, 2 H),
7.17–7.10 (m, 6 H), 6.95 (t, J = 8.4 Hz, 2 H), 5.50 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 161.99 (d, J = 245.0 Hz, CF), 140.86,
136.90, 135.85, 130.84, 130.07, 128.89, 128.72, 128.41, 127.49,
126.88, 115.47 (d, J = 21.0 Hz), 56.84.
(4-Bromophenyl)[(4-fluorophenyl)(phenyl)methyl]sulfane (4fe)
Yield: 162 mg (87%); white solid; mp 70–72 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.22 (m, 9 H), 7.07 (d, J = 8.8 Hz, 2
H), 6.98 (d, J = 8.8 Hz, 2 H), 5.49 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 161.78 (d, J = 245.7 Hz, CF), 137.25,
135.88, 134.31, 132.19, 131.73, 129.77, 129.69, 128.58, 128.50,
120.90, 115.39 (d, J = 21.0 Hz), 55.80.
[(4-Chlorophenyl)(phenyl)methyl](phenyl)sulfane (4cf)
Yield: 135 mg (87%); white solid; mp 55–57 °C.
1H NMR (400 MHz, CDCl3): δ = 7.39–7.13 (m, 14 H), 5.50 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.59, 139.71, 135.71, 133.12,
130.97, 130.70, 129.88, 128.86, 128.65, 128.43, 127.69, 127.08, 56.98.
(4-Bromophenyl)[(4-chlorophenyl)(phenyl)methyl]sulfane (4ff)
[(4-Bromophenyl)(phenyl)methyl](phenyl)sulfane (4cg)
Yield: 161 mg (83%); white solid; mp 72–74 °C.
Yield: 145 mg (82%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.41–7.36 (m, 4 H), 7.31–7.12 (m, 10
1H NMR (400 MHz, CDCl3): δ = 7.35–7.20 (m, 11 H), 7.05 (d, J = 8.4 Hz,
2 H), 5.44 (s, 1 H).
H), 5.48 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.08, 139.18, 134.78, 133.31,
132.35, 132.0, 129.83, 128.88, 128.86, 128.37, 127.76, 121.06, 56.93.
13C NMR (100 MHz, CDCl3): δ = 139.37, 139.10, 134.56, 130.61,
129.69, 129.12, 127.83, 127.66, 127.29, 126.48, 125.84, 120.14, 55.85.
(4-Bromophenyl)[(4-bromophenyl)(phenyl)methyl]sulfane (4fg)
[(4-Fluorophenyl)(phenyl)methyl](4-methoxyphenyl)sulfane
(4de)
Yield: 158 mg (73%); white solid; mp 80 °C.
1H NMR (400 MHz, CDCl3): δ = 7.43–7.41 (m, 2 H), 7.37–7.23 (m, 9 H),
7.07 (d, J = 8.4 Hz, 2 H), 5.45 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 140.03, 139.75, 134.77, 132.40,
132.02, 131.83, 130.19, 128.86, 128.37, 127.77, 121.47, 121.10, 57.05.
Yield: 157 mg (97%); white solid; mp 63 °C.
1H NMR (400 MHz, CDCl3): δ = 7.36–7.16 (m, 9 H), 6.94 (t, J = 8.8 Hz, 2
H), 6.71 (d, J = 8.8 Hz, 2 H), 5.31 (s, 1 H), 3.73 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.13 (t, J = 246.0 Hz, CF), 141.21,
137.29, 134.96, 132.80, 130.19, 130.11, 128.64, 128.45, 127.39,
125.69, 115.35 (d, J = 21.0 Hz), 114.48, 58.67, 55.34.
Benzyl[(2-chlorophenyl)(phenyl)methyl]sulfane (5ah)
Yield: 161 mg (>99%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 8.4 Hz, 1 H), 7.34–7.12 (m,
13 H), 5.43 (s, 1 H), 3.56 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 139.86, 138.42, 137.62, 133.98,
130.15, 129.81, 129.09, 128.71, 128.63, 128.56, 128.45, 127.38,
127.25, 127.16, 49.27, 37.01.
[(4-Chlorophenyl)(phenyl)methyl](4-methoxyphenyl)sulfane
(4df)
Yield: 162 mg (95%); white solid; mp 53 °C.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.36 (m, 2 H), 7.33–7.20 (m, 9 H),
6.73 (d, J = 8.4 Hz, 2 H), 5.33 (s, 1 H), 3.74 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.62, 140.90, 140.08, 134.98,
132.96, 129.95, 128.68, 128.45, 127.47, 125.54, 114.53, 58.78, 55.35.
Benzyl[(3-chlorophenyl)(phenyl)methyl]sulfane (5ai)
Yield: 161 mg (>99%); yellow liquid.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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P. Singh, R. K. Peddinti
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.36–7.28 (m, 7 H), 7.24–7.19 (m, 7 H),
4.87 (s, 1 H), 3.53 (s, 2 H).
2012, 55, 6802. (b) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T.
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(4) Dénès, F.; Schiesser, C. H.; Renaud, P. Chem. Soc. Rev. 2013, 42,
7900.
13C NMR (100 MHz, CDCl3): δ = 143.26, 140.35, 137.73, 134.48,
129.09, 128.82, 128.67, 128.61, 128.51, 127.58, 127.50, 127.24,
126.79, 52.75, 36.71.
(5) (a) Nielsen, S. F.; Nielsen, E. O.; Oslen, G. M.; Liljefors, T.; Peters,
D. J. Med. Chem. 2000, 43, 2217. (b) Wang, Y.; Chackalamannil,
S.; Hu, Z.; Clader, J. W.; Greenlee, W.; Billard, W.; Binch, H.;
Crosby, G.; Ruperto, V.; Duffy, R. A.; McQuade, R.; Lachowicz, J.
E. Bioorg. Med. Chem. Lett. 2000, 10, 2247. (c) Liu, G.; Huth, J. R.
E.; Olejniczak, E. T.; Mendoza, R.; DeVries, P.; Leitza, S.; Reilly, E.
B.; Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med. Chem.
2001, 44, 1202. (d) Parveen, S.; Khan, M. O. F.; Austin, S. E.;
Croft, S. L.; Yardly, V.; Rock, P.; Douglas, K. T. J. Med. Chem. 2005,
48, 8087.
(6) (a) Gremillion, D. H.; Winn, R. E.; Vandenbout, E. D. Antimicrob.
Agents Chemother. 1983, 23, 944. (b) Saito, H.; Sato, K.; Jin, B. W.
Antimicrob. Agents Chemother. 1984, 26, 270. (c) Barry, A. L.;
Jones, R. N.; Thornsberry, C.; Fuchs, P. C.; Ayers, L. W.; Gavan, T.
L.; Gerlach, E. H.; Sommers, H. M. J. Antimicrob. Chemother.
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Methyl 3-[(3-Chlorophenyl)(phenyl)methyl]thiopropanoate (5hi)
Yield: 159 mg (>99%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.43–7.39 (m, 3 H), 7.34–7.20 (m, 3 H),
7.25–7.19 (m, 3 H), 5.16 (s, 1 H), 3.67 (s, 3 H), 2.67 (t, J = 7.2 Hz, 2 H),
2.55 (t, J = 4.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 172.34, 139.98, 138.69, 133.76,
130.03, 129.79, 128.71, 128.57, 127.52, 127.35, 51.94, 49.91, 34.23,
27.41.
Methyl 3-[(2,4-Dichlorophenyl)(phenyl)methyl]thiopropanoate
(5hj)
Yield: 176 mg (>99%); colorless liquid.
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.0 Hz, 1 H), 7.32 (t, J = 8.4
Hz, 3 H), 7.23 (d, J = 8.4 Hz, 3 H), 7.14 (t, J = 7.6 Hz, 1 H), 5.66 (s, 1 H),
3.64 (s, 3 H), 2.67 (t, J = 7.2 Hz, 2 H), 2.56 (t, J = 6.8 Hz, 2 H).
(7) (a) Baumann, M.; Baxendale, I. R. Beilstein J. Org. Chem. 2013, 9,
2265. (b) Ning, X.; Guo, Y.; Wang, X.; Ma, X.; Tian, C.; Shi, X.;
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13C NMR (100 MHz, CDCl3): δ = 172.16, 138.64, 138.23, 133.75,
(8) (a) Chen, X.; Hussain, S.; Parveen, S.; Zhang, S.; Yang, Y.; Zhu, C.
Curr. Med. Chem. 2012, 19, 3578. (b) Al-Riyami, L.; Pineda, M. A.;
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A.-G.; Dan-Qian, X.; Xu, Z.-Y. Adv. Synth. Catal. 2014, 356, 1753.
(b) Lumsden, S. E. A.; Durgaprasad, G.; Muthiah, K. A. T.; Rose,
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133.27, 129.86, 128.84, 128.79, 127.45, 51.92, 49.90, 34.19, 27.46.
[(2-Chlorophenyl)(phenyl)methyl](o-tolyl)sulfane (5gh)
Yield: 148 mg (91%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 7.45–7.41 (m, 3 H), 7.36–7.23 (m, 6 H),
7.18–7.02 (m, 4 H), 5.49 (s, 1 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.28, 140.42, 138.40, 135.0, 134.49,
130.31, 130.27, 129.92, 128.85, 128.67, 128.48, 127.69, 127.62,
126.74, 126.56, 56.15, 20.58.
(11) Kuwano, R.; Kusano, H. Org. Lett. 2008, 10, 1979.
(12) Peñéñory, A. B.; Argüello, J. E.; Puiatti, M. Eur. J. Org. Chem. 2005,
114.
(13) Mao, J.; Jia, T.; Frensch, G.; Walsh, P. J. Org. Lett. 2014, 16, 5304.
(14) Barbieri, A.; Chimienti, R. D.; Giacco, T. D.; Stefano, S. D.;
Lanzalunga, O.; Lapi, A.; Mazzonna, M.; Olivo, G.; Salamone, M.
J. Org. Chem. 2016, 81, 2513.
(15) York, C.; Prakash, G. K. S.; Olah, G. A. Tetrahedron 1996, 52, 9.
(16) (a) Nicolaou, K. C.; Lister, T.; Denton, R. M.; Gelin, C. F. Tetrahe-
dron 2008, 64, 4736. (b) Dai, C.; Xu, Z.; Huang, F.; Yu, Z.; Gao, Y.
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[(3-Chlorophenyl)(phenyl)methyl](4-nitrophenyl)sulfane (5ii)
Yield: 147 mg (83%); yellow liquid.
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 9.2 Hz, 2 H), 7.43–7.39 (m, 3
H), 7.36–7.22 (m, 8 H), 5.68 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 146.26, 145.54, 141.62, 138.80,
134.92, 130.27, 129.18, 128.53, 128.35, 128.24, 127.48, 126.58,
124.01, 55.26.
Acknowledgment
(17) Kondo, T.; Mistudo, T. Chem. Rev. 2000, 100, 3205.
(18) Correa, A.; Carril, M.; Bolm, C. Angew. Chem. Int. Ed. 2008, 47,
2880.
P.S. thanks UGC (Delhi) for a research fellowship.
(19) Altimari, J. M.; Delaney, J. P.; Servinis, L.; Squire, J. S.; Thornton,
M. T.; Khosa, S. K.; Long, B. M.; Johnstone, M. D.; Fleming, C. L.;
Pfeffer, F. M.; Hickey, S. M.; Wride, M. P.; Ashton, T. D.; Fox, B. L.;
Byrne, N.; Henderson, L. C. Tetrahedron Lett. 2012, 53, 2035.
(20) Bandgar, B. P.; Gawande, S. S.; Muley, D. B. Green Chem. Lett. Rev.
2010, 3, 49.
Supporting Information
Supporting information for this article is available online at
https://doi.org /10.1055/s-0036-1589022.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
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Org. Chem. 2004, 69, 6904. (c) Baldovino-Pantaleon, O.;
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