Transition Metal-Free de Novo Synthesis of Sulfonated Pyrazoles from Sulfonyl Hydrazides, 1,3-Diketones, and Sodium Sulfinates at Room Temperature

Article abstract of DOI:10.1021/acs.joc.1c00171

A transition metal-free method for de novo construction of diverse sulfonated pyrazoles from readily available sulfonyl hydrazides, 1,3-diketones, and sodium sulfinates was established under mild conditions. Pyrazoles bearing two different sulfonyl groups were obtained in one step. The method features a diversity of substituents of the pyrazole products and a remarkably simple work-up.

Full text of DOI:10.1021/acs.joc.1c00171

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Article
Transition Metal-Free De Novo Synthesis of Sulfonated Pyrazoles
from Sulfonyl Hydrazides, 1,3-Diketones, and Sodium Sulfinates at
Room Temperature
Jiawen Chen,§ Dongwei Chen,§ Jinqiang Kuang,* and Yongmin Ma*
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ABSTRACT: A transition metal-free method for de novo construction of diverse sulfonated pyrazoles from readily available
sulfonyl hydrazides, 1,3-diketones, and sodium sulfinates was established under mild conditions. Pyrazoles bearing two different
sulfonyl groups were obtained in one step. The method features a diversity of substituents of the pyrazole products and a remarkably
simple work-up.
INTRODUCTION
■
Pyrazole skeletons have gained considerable attention due to
their wide existence in pharmaceuticals and biologically active
compounds,1 which shows a variety of bioactivities, e.g.
antimicrobial,2 anticancer,3 antiinflammatory,4 antiprolifera-
tion,5 agricultural insecticide,6 and antioxidation activity.7
Besides, pyrazoles also play important roles in coordinating
chemistry, organometallic chemistry, and latent fingermarks
analysis.8 In addition, substituents on the pyrazole skeleton
might also play important roles in the activities. At this point, it
is meaningful to develop efficient methods for constructing
pyrazoles bearing diverse functional groups.9 Sulfone groups,
often uncovered in biologically active molecules, agro-
chemicals, and materials, constitute one of the most valuable
sorts of organic functional groups.10 Incorporation of sulfone
group into particular skeletons is a frequently used strategy to
gain better activities during the drug design.11 Given these
viewpoints, the synthesis of sulfonated pyrazoles has evoked
lots of interest from synthetic chemists.12−15
Conventional approaches targeting this consist of cyclo-
addition of reagents in which sulfone groups were pre-installed
Received: January 22, 2021
Published: June 29, 2021
and remained untouched during the reaction and oxidation of
pyrazoles with thioether groups.12,13 In 2014, Wan et al.
reported the pioneering synthesis of sulfonated pyrazoles from
sulfonyl hydrazides and 1,3-diketones, in which sulfonyl
hydrazides function as both the ring component and sulfonyl
precursor (eq 1).14a Recently, this dual-role-sulfonyl-hydrazide
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a
Table 1. Optimization of Reaction Conditions
entry
oxidant (equiv)
I2 (2.0)
solvent
base (equiv)
isolated yield (%)
1
2
3
4
5
6
7
8
CH3CN
EA
THF
DMSO
1,4-dioxane
DMA
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
K2HPO4·3H2O (1.5)
NaHCO3 (1.5)
58
40
36
33
41
37
35
57
50
32
35
11
32
29
58
51
46
42
n.d.
11
16
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (2.0)
I2 (1.5)
I2 (1.1)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
I2 (1.5)
NMP
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
10
11
12
13
14
15
16
17
NaOAc (1.5)
K2CO3 (1.5)
KOH (1.5)
tBuOK (1.5)
K2HPO4·3H2O (0.8)
K2HPO4·3H2O (0.6)
K2HPO4 (0.8)
b
18
c
19
20
21
K2HPO4 (0.8)
K2HPO4·3H2O (0.8)
K2HPO4·3H2O (0.8)
I2 (0.2) + TBHP (3)
I2 (0.2) + DTBP (3)
a
Reaction conditions: 4-methylbenzenesulfonohydrazide (1a) (0.5 mmol), pentane-2,4-dione (2a) (0.6 mol), sodium 4-methylbenzenesulfinate
b
c
(3a) (1.0 mol), oxidant, base, solvent (4.5 mL), air, and rt. The reaction was carried out at 35 °C. n.d. = not detected.
strategy was applied to the reactions of sulfonyl hydrazides
with enaminones, affording sulfonated pyrazoles under mild
conditions (eq 2).14b,c This strategy makes full use of the
sulfonyl hydrazides involved in the reaction; however, it could
only introduce two identical sulfonyl groups to the pyrazole
skeleton. Compared to sulfonyl hydrazides, sodium sulfinates
are more environmentally benign sulfone sources. In 2017,
Wang et al. reported a molecular iodine-catalyzed direct
sulfonation of preformed pyrazolones with sodium sulfinates
(eq 3).15 Although these methods are inspiring, more general
and efficient protocols are still much in demand to get over the
existing limitations such as extra steps to prepare active
precursors, applying excess amounts of organometallic
reagents, harsh reaction conditions, tedious work-up proce-
dures, and limited substrate scope or low yields. Aiming at
developing a green, practical, and efficient method for
constructing diverse sulfonated pyrazoles, we speculated that
the target compounds might be produced from readily
available 1,3-dielectrophiles, sulfonyl hydrazides, and sodium
sulfinates, in which the latter two reagents might serve as the
sulfonyl precursors at the same time in the reaction, giving rise
to pyrazoles with more tunable structures. As a verification, we
herein reported a novel strategy for the synthesis of diverse
sulfonated pyrazoles through a molecular iodine-promoted
multicomponent reaction of sulfonyl hydrazides, 1,3-diketones,
and sodium sulfinates (eq 4).
presence of I2 (2.0 equiv) and K2HPO4·3H2O (1.5 equiv) in
CH3CN at room temperature, the desired pyrazole 4a was
obtained in 58% isolated yield (Table 1, entry 1). Other
solvents such as ethyl acetate, tetrahydrofuran (THF),
dimethyl sulfoxide (DMSO), 1,4-dioxane, dimethylacetamide
(DMA), and N-methyl-2-pyrrolidone (NMP) also work in the
reaction, albeit providing pyrazole 4a in inferior yields (Table
1, entries 2−7). A comparable yield of pyrazole 4a was
obtained when decreasing the loading of iodine to 1.5 equiv,
while further decreasing to 1.1 equiv gave only 50% yield
(Table 1, entries 8 and 9). Further investigation of other bases
revealed that K2HPO4·3H2O was the best choice (Table 1,
entries 10−14). The optimal amount of K2HPO4·3H2O was
found to be 0.8 equiv, although a 42% isolated yield of 4a was
produced at 35 °C even without K2HPO4·3H2O (Table 1,
entries 15, 16, and 18). These results indicate that the base
K2HPO4·3H2O plays a promotive part in the transformation,
but not an indispensable one. Iodine is essential in this
transformation as the desired product 4a was not observed in
the absence of iodine (Table 1, entry 19). Applying a catalytic
amount of iodine (20 mol %) and 3 equiv of additional oxidant
(TBHP or DTBP) did not yield pyrazole 4a in a satisfactory
yield; only 11 and 16% yields were obtained, respectively
(Table 1, entries 20 and 21).
With the optimal conditions in hand, we then examined the
generality of the method by applying various sulfonyl
hydrazides, 1,3-diketones, and sodium sulfinates. The scope
of sulfonyl hydrazides was first investigated. As exhibited in
Table 2, various aryl sulfonyl hydrazides bearing electron-
donating or -withdrawing substituents were compatible in this
reaction, affording pyrazoles 4a−4q in yields of 47−67% under
RESULTS AND DISCUSSION
■
Initial reactivity assays were conducted with 4-methylbenze-
nesulfonohydrazide 1a, pentane-2,4-dione 2a, and sodium
benzenesulfinate 3a as model substrates. To our delight, in the
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a
Table 2. Substrate Scope of Sulfonyl Hydrazides
a
Reaction conditions: 1 (0.5 mmol), 2a (0.6 mmol), 3 (1.0 mmol), l2 (0.75 mmol), K2HPO4 3H2O (0.4 mmol), CH3CN (4.5 mL), air, rt, and 22
h.
a
Table 3. Substrate Scope of 1,3-Diketones
a
Reaction conditions: 1a (0.5 mmol), 2 (0.6 mmol), 3b (1.0 mmol), l2 (0.75 mmol), K2HPO4·3H2O (0.4 mmol), CH3CN (4.5 mL), air, rt, and 22
h.
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a
Table 4. Substrate Scope of Sodium Sulfinates
a
Reaction conditions: 1a (0.5 mmol), 2d (0.6 mmol), 3 (1.0 mmol), l2 (0.75 mmol), K2HPO4·3H2O (0.4 mmol), CH3CN (4.5 mL), air, rt, and 22
b
c
h. Sodium ethanesulfinate (2.0 mmol) was used. Sodium trifluoromethanesulfinate (2.0 mmol) was used.
mild reaction conditions. The electronic properties of the
substituents on the aromatic ring of aryl sulfonyl hydrazides
did not show much influence on yields. It is notable that the
functional groups such as fluoro, chloro, bromo, iodo, nitro,
and cyano were well tolerated in this transformation, allowing
the further elaboration of the corresponding products.
Heteroaryl sulfonyl hydrazides such as quinoline-8-sulfonohy-
drazide and thiophene-2-sulfonohydrazide were also suitable
substrates in the reaction, producing the corresponding
pyrazoles 4r and 4s in 51% yields. Remarkably, the aliphatic
sulfonyl hydrazide, which was ineffective in the previous
report,14 was an adaptable substrate as well in this protocol,
affording pyrazole 4t in a 45% isolated yield.
To test the practicality of the method for the synthesis of
fully substituted pyrazoles, a gram-scale reaction was carried
out. Under the standard conditions, the reaction of 4-
methylbenzenesulfonohydrazide (1a, 4.0 mmol), 1-phenyl-
butane-1,3-dione (2d, 4.8 mmol), and sodium p-toluenesulfi-
nate (3b, 8.0 mmol) proceeded smoothly, providing 1.57 g of
pyrazole 4w in 84% yield (eq 5). It is remarkable that the pure
product was obtained through a simple filtration, thus
dramatically reducing the time and solvents consumed during
the conventional work-up.
Next, the reactivity of nonsymmetrical 1,3-diketones in this
reaction was surveyed with 4-methylbenzenesulfonohydrazide
(1a) and sodium p-toluenesulfinate (3b) under the standard
conditions. As shown in Table 3, a variety of nonsymmetrical
1,3-diketones were suitable substrates in this method. When 6-
methylheptane-2,4-dione was applied in the protocol, the
corresponding pyrazole 4u was produced in 70% yield and
excellent regioselectivity.16 Nonane-2,4-dione, which contains
a longer carbon chain, was also smoothly converted into the
desired product 4v in 56% yield under the optimal conditions.
The investigation was then directed to 1,3-diketones with an
aryl group. 1-Phenylbutane-1,3-dione proved to be quite active
under the standard conditions, furnishing 4w in 80% yield. In
addition, 1-arylbutane-1,3-diones bearing methoxy, fluoro,
chloro, and bromo substituents on the aryl ring were all
compatible in the reaction, yielding the corresponding
functionalized pyrazole products in 68−76% yields (Table 3,
4y and 4A-4D). 1,3-Diketones with a heteroaryl group such as
benzo[b]thiophen-2-yl, 3-thiophenyl, 2-furanyl, and 2-pyridinyl
suited the standard conditions as well, constructing pyrazoles
4E−4H with two heteroaryl rings in 49−65% yields.
The generality of sodium sulfinates was examined by the
reaction with 4-methylbenzenesulfonohydrazide (1a) and 1-
phenylbutane-1,3-dione (2d) (Table 4). Sodium 4-chloroben-
zene sulfinate (3c) and sodium 4-fluorobenzene sulfinate (3d)
were less effective than sodium p-toluenesulfinate (3b) in this
method, generating the corresponding products 4I and 4J in
62 and 58% yield (vs 4w, 80%), respectively. Encouragingly,
aliphatic sodium sulfinate, e.g., sodium ethanesulfinate, was fit
with the protocol as well, furnishing pyrazole 4K in 64% yield
under slightly modified conditions. The Langlois reagent
(CF3SO2Na) also survived in the reaction; however, only 24%
yield of product 4L was obtained.
To gain more insight into the mechanism of the reaction,
some control experiments were carried out. Under the
standard conditions, the desired product 4a was not detected
when pyrazole 5 was subjected to the reaction (Scheme 1a),
indicating that the reaction would probably not proceed
through a cyclization−sulfonylation process. When a radical
scavenger 2,6-di-tert-butyl-4-methylphenol (BHT) or 2,2,6,6-
tetramethylpiperidine-N-oxyl (TEMPO) was added to the
reaction system, the desired product 4a was provided in 49 and
56% yield, respectively (Scheme 1b,c), showing little influence
on the reaction effectivity. These results suggested that a
radical process was not likely involved in this method.
Based on the results of control experiments, a plausible
mechanism for the reaction is depicted in Scheme 2. Sulfonyl
iodide 6 is easily generated from sodium sulfinate 3 and
molecular iodine.15,17 The condensation of sulfonyl hydrazide
and 1,3-diketone afforded imine 7, which then undergoes
tautomerization to produce its enol form 8. A following
nucleophilic attack of the enol form 8 toward the in situ
generated sulfonyl iodide 6 yields intermediate 9, which finally
produces the desired product 4 by an intramolecular
condensation.
CONCLUSIONS
■
To conclude, a molecular iodine-promoted transition metal-
free method for the synthesis of sulfonated pyrazoles from
readily available sulfonyl hydrazides, 1,3-diketones, and sodium
sulfinates has been established under mild conditions. Sulfonyl
hydrazides and sodium sulfinates each offer a sulfonyl group in
the reaction, improving the diversity of the desired products.
The protocol features broad substrate scope and easy
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Scheme 1. Control Experiments
Scheme 2. Plausible Reaction Mechanism
for 22 h. It was then quenched (consumption of residual I2) with
saturated Na2S2O3 solution, forming a white precipitate. Filtration of
the suspension gave the crude product. The crude product was
washed with water (15 mL) and petroleum ether (15 mL)
sequentially to afford pure product 4.
manipulation. Considering its green conditions and simple
operation, the protocol might be fairly appealing in synthetic
chemistry. Further mechanistic study and elaboration of the
methodology to construct other diversely substituted hetero-
cyclic compounds is being pursued in our laboratory.
3,5-Dimethyl-4-(phenylsulfonyl)-1-tosyl-1H-pyrazole (4a). The
title compound was obtained as a white solid (113.6 mg, 58%). Mp
120−122 °C.
EXPERIMENTAL SECTION
■
1H NMR (400 MHz, CDCl3) δ 7.90−7.83 (m, 4H), 7.61 (t, J = 7.4
Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 2.86 (s,
3H), 2.45 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
151.1, 146.8, 146.5, 142.0, 133.7, 133.4, 130.2, 129.2, 128.1, 126.5,
121.3, 21.7, 21.6, 13.6, 11.6; HRMS (TOFMS) m/z [M + Na]+ calcd
for C18H18N2O4S2Na: 413.0606; found: 413.0610.
General Methods. All commercially available reagents were used
without further purification. Analytical TLC was performed on glass-
backed plates precoated with silica gel, which were visualized by UV
1
fluorescence (λmax = 254 nm). H NMR and 13C NMR spectra were
recorded on a Bruker 400 MHz spectrometer (1H: 400 MHz; 13C:
100 MHz), using CDCl3 as the solvent with tetramethylsilane (TMS)
as an internal standard at room temperature. All 1H NMR spectra are
reported in parts per million (ppm) downfield of TMS and were
measured relative to the signals at 0 ppm (TMS). All 13C NMR
spectra were reported in ppm relative to the residual CHCl3 (77.0
3,5-Dimethyl-1,4-ditosyl-1H-pyrazole (4b).14a,b The title com-
pound was obtained as a white solid (127.3 mg, 63%). Mp 123−125
°C.
1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 2H), 7.73 (d, J
= 8.0 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.85
(s, 3H), 2.44 (s, 3H), 2.41 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 151.1, 146.6, 146.5, 144.5, 139.2, 133.9, 130.2, 129.9,
128.1, 126.6, 121.7, 21.7, 21.5, 13.6, 11.6.
1
1
ppm) and were obtained with H-decoupling. Data for H NMR are
described as follows: chemical shift (δ in ppm), multiplicity (s, singlet;
d, doublet; t, triplet; q, quartet; quin, quintet; sep, septet; m,
multiplet; br, broad signal), coupling constant (Hz), integration. Data
for 13C NMR are described in terms of chemical shift (δ in ppm).
High-resolution mass spectra were recorded on an ESI-Q-TOF mass
spectrometer. Melting points were measured on the X4 melting point
apparatus and uncorrected.
3,5-Dimethyl-1-(phenylsulfonyl)-4-tosyl-1H-pyrazole (4c). The
title compound was obtained as a white solid (116.2 mg, 59%). Mp
155−156 °C.
1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 2H), 7.77−
7.66 (m, 3H), 7.58 (t, J = 7.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.86
(s, 3H), 2.42 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.3, 146.8, 144.5, 139.1, 136.9, 135.0, 129.9, 129.6, 128.0,
126.6, 121.9, 21.5, 13.6, 11.7; HRMS (TOFMS) m/z [M + Na]+
calcd for C18H18N2O4S2Na: 413.0606; found: 413.0615.
1-([1,1′-Biphenyl]-4-ylsulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4d). The title compound was obtained as a white solid (123.3 mg,
53%). Mp 162−164 °C.
Sulfonyl hydrazides18 and 1,3-diketones19 were prepared according
to the reported procedures.
General Procedure for the Synthesis of Pyrazoles 4. To a
Schlenk tube (10 mL) were added sulfonyl hydrazide (0.5 mmol),
1,3-diketone (0.6 mmol, 1.2 equiv), sodium sulfinate (1.0 mmol, 2.0
equiv), K2HPO4·3H2O (0.4 mmol, 0.8 equiv), I2 (0.75 mmol, 1.5
equiv), and 4.5 mL of CH3CN sequentially under air. Then, the tube
was sealed and the reaction mixture was stirred at room temperature
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1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.4 Hz, 2H), 7.79−
7.72 (m, 4H), 7.59 (d, J = 8.0 Hz, 2H), 7.53−7.41 (m, 3H), 7.32 (d, J
= 8.0 Hz, 2H), 2.89 (s, 3H), 2.42 (s, 3H), 2.38 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 151.4, 148.1, 146.8, 144.6, 139.2, 138.5,
135.2, 129.9, 129.1, 129.0, 128.7, 128.2, 127.4, 126.7, 121.9, 21.5,
13.7, 11.8; HRMS (TOFMS) m/z [M + Na]+ calcd for
C24H22N2O4S2Na: 489.0919; found: 489.0923.
1H NMR (400 MHz, CDCl3) δ 8.06−8.00 (m, 2H), 7.74 (d, J =
8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.29−7.22 (m, 2H), 2.86 (s,
3H), 2.43 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
166.4 (d, J = 257.8 Hz), 151.5, 146.8, 144.6, 139.1, 132.9 (d, J = 3.9
Hz), 131.3 (d, J = 9.3 Hz), 129.9, 126.7, 122.0, 117.0 (d, J = 22.8 Hz),
21.5, 13.6, 11.7; HRMS (TOFMS) m/z [M + Na]+ calcd for
C18H17FN2O4S2Na: 431.0511; found: 431.0517.
3,5-Dimethyl-1-(naphthalen-2-ylsulfonyl)-4-tosyl-1H-pyrazole
(4e). The title compound was obtained as a white solid (125.0 mg,
56%). Mp 148−150 °C.
1-((4-Chlorophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4l). The title compound was obtained as a white solid (140.6 mg,
66%). Mp 159−160 °C.
1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.00 (t, J = 9.0 Hz,
2H), 7.92 (d, J = 8.0 Hz, 2H), 7.83(dd, J = 8.6, 1.4 Hz, 2H), 7.76−
7.62 (m, 4H), 7.30 (d, J = 8.0 Hz, 2H), 7.53−7.41 (m, 3H), 7.32 (d, J
= 8.0 Hz, 2H), 2.91 (s, 3H), 2.40 (s, 3H), 2.36 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 151.3, 146.8, 144.5, 139.1, 135.7, 133.6,
131.8, 130.4, 130.1, 130.0, 129.9, 129.6, 128.1, 128.0, 126.6, 122.0,
121.9, 21.5, 13.6, 11.8; HRMS (TOFMS) m/z [M + Na]+ calcd for
C22H20N2O4S2Na: 463.0762; found: 463.0765.
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 2H), 7.74 (d, J
= 8.4 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.32 (t, J = 8.0 Hz, 2H), 2.86
(s, 3H), 2.43 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.7, 146.9, 144.6, 142.0, 139.1, 135.3, 130.0, 129.6, 126.7,
122.1, 21.5, 13.7, 11.7; HRMS (TOFMS) m/z [M + Na]+ calcd for
C18H17ClN2O4S2Na: 447.0216; found: 447.0225.
1-((4-Bromophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4m). The title compound was obtained as a white solid (126.7 mg,
54%). Mp 198−199 °C.
1-((4-(Tert-butyl)phenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyra-
zole (4f). The title compound was obtained as a white solid (114.3
mg, 51%). Mp 151−152 °C.
1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.77−
7.68 (m, 4H), 7.32 (d, J = 8.0 Hz, 2H), 2.85 (s, 3H), 2.42 (s, 3H),
2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.7, 146.9,
144.6, 139.1, 135.8, 133.0, 130.7, 130.0, 129.6, 126.7, 122.1, 21.5,
13.7, 11.7; HRMS (TOFMS) m/z [M + Na]+ calcd for
C18H17BrN2O4S2Na: 490.9711; found: 490.9715.
1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.8 Hz, 2H), 7.74 (d, J
= 8.0 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 2.84
(s, 3H), 2.41 (s, 3H), 2.37 (s, 3H), 1.34 (s, 9H); 13C{1H} NMR (100
MHz, CDCl3) δ 159.3, 151.2, 146.7, 144.5, 139.2, 133.8, 129.9, 128.0,
126.69, 126.66, 121.8, 35.4, 30.9, 21.5, 13.7, 11.7; HRMS (TOFMS)
m/z [M + Na]+ calcd for C22H26N2O4S2Na: 469.1232; found:
469.1232.
1-((4-Iodophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4n). The title compound was obtained as a white solid (149.2 mg,
58%). Mp 184−186 °C.
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 2H), 7.73 (d, J
= 8.4 Hz, 2H), 7.68 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.85
(s, 3H), 2.42 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.6, 146.9, 144.6, 139.1, 138.9, 136.4, 129.9, 129.2, 126.7,
122.1, 103.5, 21.5, 13.7, 11.7; HRMS (TOFMS) m/z [M + Na]+
calcd for C18H17IN2O4S2Na: 538.9572; found: 538.9573.
3,5-Dimethyl-1-((4-nitrophenyl)sulfonyl)-4-tosyl-1H-pyrazole
(4o). The title compound was obtained as a white solid (115.2 mg,
53%). Mp 228−230 °C.
3,5-Dimethyl-1-(m-tolylsulfonyl)-4-tosyl-1H-pyrazole (4g). The
title compound was obtained as a white solid (132.2 mg, 66%). Mp
130−131 °C.
1H NMR (400 MHz, CDCl3) δ 7.82−7.76 (m, 2H), 7.74 (d, J =
8.4 Hz, 2H), 7.52−7.40 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.85 (s,
3H), 2.44 (s, 3H), 2.42 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 151.2, 146.7, 144.5, 140.1, 139.2, 136.7, 135.9, 129.9,
129.4, 128.2, 126.6, 125.2, 121.8, 21.5, 21.2, 13.6, 11.7; HRMS
(TOFMS) m/z [M + Na]+ calcd for C19H20N2O4S2Na: 427.0762;
found: 427.0767.
1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 9.2 Hz, 2H), 8.21 (d, J
= 8.8 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 2.89
(s, 3H), 2.43 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 152.5, 151.3, 147.5, 144.9, 142.3, 139.0, 130.1, 129.8, 126.8,
124.8, 122.8, 21.6, 13.7, 11.8; HRMS (TOFMS) m/z [M + Na]+
calcd for C18H17N3O6S2Na: 458.0456; found: 458.0459.
1-((4-Methoxyphenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4h). The title compound was obtained as a white solid (121.5 mg,
58%). Mp 132−135 °C.
1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 2H), 7.73 (d, J
= 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.89
(s, 3H), 2.84 (s, 3H), 2.42 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 164.8, 151.0, 146.4, 144.5, 139.3, 130.7, 129.9, 128.0,
126.7, 121.6, 114.8, 55.8, 21.5, 13.7, 11.7; HRMS (TOFMS) m/z [M
+ Na]+ calcd for C19H20N2O5S2Na: 443.0711; found: 443.0720.
1-(Mesitylsulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole (4i). The
title compound was obtained as a white solid (132.3 mg, 61%). Mp
181−182 °C.
1-((4-Cyanophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4p). The title compound was obtained as a white solid (130.7 mg,
63%). Mp 210−211 °C.
1H NMR (400 MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 2H), 7.87 (d, J
= 8.4 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 2.88
(s, 3H), 2.43 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 152.3, 147.4, 144.8, 140.8, 138.9, 133.3, 130.0, 128.9, 126.8,
122.6, 118.7, 116.6, 55.8, 21.6, 13.7, 11.8; HRMS (TOFMS) m/z [M
+ Na]+ calcd for C19H17N3O4S2Na: 438.0560; found: 438.0558.
1-((2-Chlorophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4q). The title compound was obtained as a white solid (110.4 mg,
52%). Mp 139−141 °C.
1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 2H), 7.31 (d, J
= 8.0 Hz, 2H), 6.99 (s, 2H), 2.82 (s, 3H), 2.53 (s, 6H), 2.42 (s, 3H),
2.31 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 150.0, 146.3,
145.2, 144.4, 141.1, 139.4, 132.2, 131.3, 129.9, 126.7, 120.9, 22.5,
21.5, 21.1, 13.6, 11.5; HRMS (TOFMS) m/z [M + Na]+ calcd for
C21H24N2O4S2Na: 455.1075; found: 455.1084.
1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 8.0 Hz, 1H), 7.75 (d, J
= 8.4 Hz, 2H), 7.62 (td, J = 7.8, 1.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H),
7.33 (d, J = 8.0 Hz, 2H), 2.95 (s, 3H), 2.43 (s, 3H), 2.30 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.5, 148.9, 144.5, 139.3,
3,5-Dimethyl-4-tosyl-1-((2,4,6-triisopropylphenyl)sulfonyl)-1H-
pyrazole (4j). The title compound was obtained as a white solid
(120.8 mg, 47%). Mp 145−147 °C.
1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4 Hz, 2H), 7.30 (d, J
= 8.0 Hz, 2H), 7.19 (s, 2H), 4.01 (sep, J = 6.7 Hz, 2H), 2.92 (sep, J =
6.9 Hz, 1H), 2.73 (s, 3H), 2.42 (s, 3H), 2.34 (s, 3H), 1.26 (d, J = 6.8
Hz, 6H), 1.13 (d, J = 6.8 Hz, 12H); 13C{1H} NMR (100 MHz,
CDCl3) δ 155.5, 152.1, 149.5, 145.5, 144.3, 139.5, 130.2, 129.8, 126.6,
124.2, 121.0, 34.2, 29.6, 24.2, 23.3, 21.5, 13.4, 13.1; HRMS (TOFMS)
m/z [M + Na]+ calcd for C27H36N2O4S2Na: 539.2014; found:
539.2015.
135.9, 134.8, 132.9, 132.4, 132.2, 129.9, 127.6, 126.6, 121.2, 21.5,
13.6, 12.1; HRMS (TOFMS) m/z [M + Na]+ calcd for
C18H17ClN2O4S2Na: 447.0216; found: 447.0219.
8-((3,5-Dimethyl-4-tosyl-1H-pyrazol-1-yl)sulfonyl)quinoline (4r).
The title compound was obtained as a white solid (112.7 mg, 51%).
Mp 204−206 °C.
1H NMR (400 MHz, CDCl3) δ 8.73 (dd, J = 8.4, 1.6 Hz, 1H), 8.68
(dd, J = 7.2, 1.2 Hz, 1H), 8.22 (dd, J = 8.4, 1.6 Hz, 1H), 8.15 (dd, J =
8.4, 1.2 Hz, 1H), 7.78−7.68 (m, 3H), 7.48 (dd, J = 8.4, 4.4 Hz, 1H),
7.31 (d, J = 8.4 Hz, 2H), 3.24 (s, 3H), 2.44 (s, 3H), 2.22 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.3, 151.2, 151.0, 144.2,
1-((4-Fluorophenyl)sulfonyl)-3,5-dimethyl-4-tosyl-1H-pyrazole
(4k). The title compound was obtained as a white solid (135.5 mg,
67%). Mp 182−184 °C.
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143.4, 139.8, 136.6, 135.7, 134.0, 133.4, 129.8, 128.7, 126.6, 125.5,
122.5, 120.5, 21.5, 13.7, 12.6; HRMS (TOFMS) m/z [M + Na]+
calcd for C21H19N3O4S2Na: 464.0715; found: 464.0717.
3,5-Dimethyl-1-(thiophen-2-ylsulfonyl)-4-tosyl-1H-pyrazole (4s).
The title compound was obtained as a white solid (101.3 mg, 51%).
Mp 146−147 °C.
3-Methyl-5-(naphthalen-1-yl)-1,4-ditosyl-1H-pyrazole (4z). The
title compound was obtained as a white solid (193.4 mg, 75%). Mp
200−203 °C.
1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.0 Hz, 1H), 7.81 (d, J
= 8.4 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.45−7.35 (m, 3H), 7.29−
7.21 (m, 1H), 7.11 (d, J = 7.6 Hz, 2H), 7.08−6.99 (m, 3H), 6.76 (d, J
= 8.0 Hz, 2H), 6.67 (d, J = 8.8 Hz, 1H), 2.68 (s, 3H), 2.36 (s, 3H),
2.12 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.0, 146.3,
145.8, 143.9, 137.5, 133.3, 132.6, 132.0, 130.7, 129.7, 129.5, 128.9,
128.5, 128.0, 127.1, 126.3, 125.7, 125.1, 124.9, 124.3, 123.8, 21.6,
21.2, 14.2; HRMS (TOFMS) m/z [M + Na]+ calcd for
C28H24N2O4S2Na: 539.1075; found: 539.1082.
1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 3.6, 1.2 Hz, 1H), 7.79
(dd, J = 4.8, 1.2 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz,
2H), 7.16 (t, J = 4.6 Hz, 1H), 2.88 (s, 3H), 2.43 (s, 3H), 2.38 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.5, 146.8, 144.6, 139.1,
136.4, 136.2, 135.8, 129.9, 128.1, 126.7, 122.1, 21.5, 13.7, 11.8;
HRMS (TOFMS) m/z [M + Na]+ calcd for C16H16N2O4S3Na:
419.0170; found: 419.0175.
5-(4-Fluorophenyl)-3-methyl-1,4-ditosyl-1H-pyrazole (4A). The
title compound was obtained as a white solid (172.4 mg, 71%). Mp
177−180 °C.
3,5-Dimethyl-1-(propylsulfonyl)-4-tosyl-1H-pyrazole (4t). The
title compound was obtained as a white solid (80.9 mg, 45%). Mp
97−98 °C.
1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.33−
7.23 (m, 4H), 7.14 (d, J = 7.6 Hz, 2H), 7.11−7.03 (m, 4H), 7.15 (d, J
= 8.0 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 2.55 (s, 3H), 2.44 (s, 3H),
2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.8 (d, J = 250.3
Hz), 151.0, 146.7 (d, J = 23.6 Hz), 144.4, 138.5, 133.8, 132.8 (d, J =
8.6 Hz), 130.0, 129.4, 128.3, 127.0, 124.3, 122.1 (d, J = 3.3 Hz),
114.8, 114.6, 21.7, 21.4, 14.0; HRMS (TOFMS) m/z [M + Na]+
calcd for C24H21N2O4S2FNa: 507.0824; found: 507.0836.
5-(4-Chlorophenyl)-3-methyl-1,4-ditosyl-1H-pyrazole (4B).14b
The title compound was obtained as a white solid (190.8 mg,
76%). Mp 189−191 °C.
1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 2H), 7.33 (d, J
= 8.4 Hz, 2H), 3.51−3.42 (m, 2H), 2.83 (s, 3H), 2.43 (s, 6H), 1.83−
1.71 (m, 2H), 1.04 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.4, 147.6, 144.6, 139.2, 130.0, 126.6, 121.6, 56.2, 21.5,
16.5, 13.6, 12.4, 11.5; HRMS (TOFMS) m/z [M + Na]+ calcd for
C15H20N2O4S2Na: 379.0762; found: 379.0762.
5-Isobutyl-3-methyl-1,4-ditosyl-1H-pyrazole (4u).14a The title
compound was obtained as a white solid (155.8 mg, 70%). Mp
166−167 °C.
1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 2H), 7.71 (d, J
= 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 3.29
(d, J = 7.6 Hz, 2H), 2.44 (s, 3H), 2.42 (s, 3H), 2.29−2.17 (m, 4H),
0.98 (s, 3H), 0.97 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
151.4, 151.3, 146.3, 144.3, 139.3, 134.2, 129.9, 129.7, 128.4, 126.8,
121.4, 32.8, 30.1, 22.1, 21.7, 21.5, 13.7.
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.36 (d, J
= 8.0 Hz, 2H), 7.34−7.24 (m, 4H), 7.15 (d, J = 7.6 Hz, 2H), 7.03 (d,
J = 8.4 Hz, 2H), 2.55 (s, 3H), 2.44 (s, 3H), 2.38 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 151.2, 146.7, 146.6, 144.6, 138.5, 136.7,
133.8, 132.0, 130.0, 129.5, 128.4, 127.8, 127.1, 124.7, 124.1, 21.7,
21.5, 14.0.
3-Methyl-5-pentyl-1,4-ditosyl-1H-pyrazole (4v). The title com-
pound was obtained as a white solid (128.8 mg, 56%). Mp 111−113
°C.
5-(4-Bromophenyl)-3-methyl-1,4-ditosyl-1H-pyrazole (4C). The
title compound was obtained as a white solid (203.3 mg, 74%). Mp
185−187 °C.
1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz, 2H), 7.73 (d, J
= 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H),
3.30−3.22 (m, 2H), 2.45 (s, 3H), 2.42 (s, 3H), 2.33 (s, 3H), 1.63−
1.49 (m, 2H), 1.47−1.28 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 151.8, 151.3, 146.4, 144.4, 139.3, 134.1,
130.0, 129.8, 128.3, 126.8, 120.8, 31.9, 30.2, 25.4, 22.1, 21.7, 21.5,
13.9, 13.7; HRMS (TOFMS) m/z [M + Na]+ calcd for
C23H28N2O4S2Na: 483.1388; found: 483.1388.
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H), 7.52 (d, J
= 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.15
(d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.4 Hz, 2H), 2.55 (s, 3H), 2.44 (s,
3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.1, 146.6,
146.5, 144.5, 138.4, 133.7, 132.2, 130.7, 130.0, 129.5, 128.3, 127.1,
125.2, 124.9, 124.4, 21.7, 21.5, 13.9; HRMS (TOFMS) m/z [M+H]+
calcd for C24H22N2O4S2Br: 545.0204; found: 545.0204.
5-(3-Chlorophenyl)-3-methyl-1,4-ditosyl-1H-pyrazole (4D). The
title compound was obtained as a white solid (166.5 mg, 66%). Mp
162−164 °C.
3-Methyl-5-phenyl-1,4-ditosyl-1H-pyrazole (4w).14a,b The title
compound was obtained as a white solid (187.8 mg, 80%). Mp 184−
186 °C.
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.2 Hz, 2H), 7.48 (d, J
= 8.0 Hz, 1H), 7.39−7.27 (m, 5H), 7.15 (d, J = 7.2 Hz, 2H), 7.05 (d,
J = 7.2 Hz, 1H), 6.78 (s, 1H), 2.58 (s, 3H), 2.45 (s, 3H), 2.39 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.0, 146.7, 145.7, 144.6,
1H NMR (400 MHz, CDCl3) δ 7.56−7.48 (m, 3H), 7.37 (t, J = 7.8
Hz, 2H), 7.30−7.22 (m, 4H), 7.13−7.03 (m, 4H), 2.57 (s, 3H), 2.42
(s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.0,
147.8, 146.4, 144.2, 138.5, 133.8, 130.6, 130.1, 129.9, 129.3, 128.3,
127.3, 127.1, 126.2, 124.1, 21.7, 21.5, 14.0.
138.3, 133.7, 133.5, 130.3, 130.2, 130.1, 129.5, 128.9, 128.8, 128.4,
128.0, 127.2, 124.5, 21.7, 21.5, 14.0; HRMS (TOFMS) m/z [M +
Na]+ calcd for C24H21N2O4S2ClNa: 523.0529; found: 523.0540.
5-(Benzo[b]thiophen-2-yl)-3-methyl-1,4-ditosyl-1H-pyrazole
(4E). The title compound was obtained as a white solid (168.4 mg,
65%). Mp 199−201 °C.
3-Methyl-5-(p-tolyl)-1,4-ditosyl-1H-pyrazole (4x). The title com-
pound was obtained as a white solid (173.7 mg, 72%). Mp 186−187
°C.
1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.34−
7.23 (m, 4H), 7.19 (d, J = 7.6 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 6.98
(d, J = 7.6 Hz, 2H), 2.54 (s, 3H), 2.47 (s, 3H), 2.43 (s, 3H), 2.37 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.0, 148.2, 146.3, 144.2,
140.3, 138.6, 133.9, 130.5, 129.8, 129.3, 128.3, 128.1, 127.1, 124.0,
123.1, 21.6, 21.5, 21.4, 14.0; HRMS (TOFMS) m/z [M + Na]+ calcd
for C25H24N2O4S2Na: 503.1075; found: 503.1083.
1H NMR (400 MHz, CDCl3) δ 7.87−7.78 (m, 2H), 7.69 (d, J =
7.6 Hz, 2H), 7.49−7.36 (m, 4H), 7.27 (d, J = 7.2 Hz, 2H), 7.14 (s,
1H), 7.03 (d, J = 7.6 Hz, 2H), 2.57 (s, 3H), 2.43 (s, 3H), 2.32 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.2, 146.7, 144.5, 141.7,
140.4, 138.2, 137.9, 133.6, 130.0, 129.8, 129.4, 128.6, 127.4, 126.0,
125.6, 124.75, 124.72, 124.5, 122.0, 21.7, 21.5, 14.1; HRMS
(TOFMS) m/z [M + Na]+ calcd for C26H22N2O4S3Na: 545.0639;
found: 545.0650.
5-(4-Methoxyphenyl)-3-methyl-1,4-ditosyl-1H-pyrazole (4y).14b
The title compound was obtained as a white solid (169.7 mg,
68%). Mp 211−213 °C.
3-Methyl-5-(thiophen-3-yl)-1,4-ditosyl-1H-pyrazole (4F). The
title compound was obtained as a white solid (141.1 mg, 60%). Mp
206−208 °C.
1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.6 Hz, 2H), 7.32−
7.21 (m, 4H), 7.12 (d, J = 7.2 Hz, 2H), 7.01 (d, J = 7.6 Hz, 2H), 6.89
(d, J = 7.6 Hz, 2H), 3.90 (s, 3H), 2.55 (s, 3H), 2.42 (s, 3H), 2.36 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.0, 151.0, 148.2, 146.3,
144.2, 138.7, 134.0, 132.2, 129.9, 129.3, 128.3, 127.1, 124.1, 117.9,
112.8, 55.3, 21.7, 21.5, 14.1.
1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 2H), 7.35−
7.22 (m, 6H), 7.12 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 4.4 Hz, 1H), 2.57
(s, 3H), 2.42 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.1, 146.5, 144.3, 143.3, 138.5, 133.8, 129.9, 129.7, 129.4,
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128.3, 127.04, 124.8, 124.6, 124.4, 21.7, 21.5, 14.1; HRMS (TOFMS)
m/z [M + Na]+ calcd for C22H20N2O4S3Na: 495.0483; found:
495.0490.
quenched (consumption of residual I2) with saturated Na2S2O3
solution, forming a white precipitate. Filtration of the suspension
gave the crude product. Washing the crude product with water (100
mL) and petroleum ether (100 mL) sequentially afforded the pure
product 4w as a white solid (1.57 g, 84%).
5-(Furan-2-yl)-3-methyl-1,4-ditosyl-1H-pyrazole (4G). The title
compound was obtained as a white solid (124.5 mg, 54%). Mp 194−
196 °C.
1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.64−
7.59 (m, 1H), 7.51 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.22
(d, J = 8.0 Hz, 2H), 6.72 (d, J = 3.6 Hz, 1H), 6.63−6.58 (m, 1H),
2.50 (s, 3H), 2.44 (s, 3H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 151.2, 146.6, 144.62, 144.56, 138.5, 137.5, 136.8, 133.7,
130.0, 129.6, 128.6, 127.2, 125.7, 116.3, 111.3, 21.7, 21.5, 13.9;
HRMS (TOFMS) m/z [M + Na]+ calcd for C22H20N2O5S2Na:
479.0711; found: 479.0717.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00171.
■
sı
1H NMR and 13C NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
2-(3-Methyl-1,4-ditosyl-1H-pyrazol-5-yl)pyridine (4H). The title
compound was obtained as a white solid (114.5 mg, 49%). Mp 196−
198 °C.
Jinqiang Kuang − School of Pharmaceutical and Materials
Engineering, Taizhou University, Taizhou 318000, P. R.
China; Institute of Advanced Studies, Taizhou University,
Taizhou 318000, P. R. China; orcid.org/0000-0002-
7085-4023; Email: jinqiangkuang@163.com
Yongmin Ma − School of Pharmaceutical and Materials
Engineering, Taizhou University, Taizhou 318000, P. R.
China; Institute of Advanced Studies, Taizhou University,
Taizhou 318000, P. R. China; Email: yongmin.ma@
tzc.edu.cn
1H NMR (400 MHz, CDCl3) δ 8.75−8.70 (m, 1H), 7.88−7.80 (m,
3H), 7.57 (d, J = 8.4 Hz, 2H), 7.50−7.43 (m, 2H), 7.32 (d, J = 8.0
Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 2.43 (s, 6H), 2.38 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.1, 148.8, 146.9, 146.43,
146.39, 144.4, 138.6, 135.6, 133.7, 130.0, 129.6, 128.8, 127.3, 126.6,
124.5, 123.7, 21.8, 21.5, 13.5; HRMS (TOFMS) m/z [M + Na]+
calcd for C23H21N3O4S2Na: 490.0871; found: 490.0877.
4-((4-Chlorophenyl)sulfonyl)-3-methyl-5-phenyl-1-tosyl-1H-pyr-
azole (4I). The title compound was obtained as a white solid (152.1
mg, 62%). Mp 191−194 °C.
1H NMR (400 MHz, CDCl3) δ 7.58−7.49 (m, 3H), 7.38 (t, J = 7.8
Hz, 2H), 7.32−7.23 (m, 6H), 7.04 (d, J = 7.2 Hz, 2H), 2.58 (s, 3H),
2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 150.8, 147.9,
146.5, 139.8, 139.7, 133.6, 130.5, 130.2, 129.9, 128.9, 128.5, 128.3,
127.4, 125.9, 123.4, 21.6, 14.0; HRMS (TOFMS) m/z [M + Na]+
calcd for C23H19N2O4S2ClNa: 509.0372; found: 509.0376.
4-((4-Fluorophenyl)sulfonyl)-3-methyl-5-phenyl-1-tosyl-1H-pyr-
azole (4J). The title compound was obtained as a white solid (136.8
mg, 58%). Mp 181−183 °C.
Authors
Jiawen Chen − School of Pharmaceutical and Materials
Engineering, Taizhou University, Taizhou 318000, P. R.
China
Dongwei Chen − School of Pharmaceutical and Materials
Engineering, Taizhou University, Taizhou 318000, P. R.
China
1H NMR (400 MHz, CDCl3) δ 7.57−7.48 (m, 3H), 7.42−7.32 (m,
4H), 7.30−7.23 (m, 2H), 7.04 (d, J = 7.6 Hz, 2H), 6.96 (t, J = 8.4 Hz,
2H), 2.58 (s, 3H), 2.43 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
165.3 (d, J = 254.5 Hz), 150.9, 147.8, 146.5, 137.4 (d, J = 3.4 Hz),
133.7, 130.6, 130.3, 129.94 (d, J = 9.8 Hz), 129.93, 128.3, 127.5,
126.0, 123.6, 115.9 (d, J = 22.1 Hz), 21.7, 14.1; HRMS (TOFMS) m/
z [M + Na]+ calcd for C23H19N2O4S2FNa: 493.0668; found:
493.0674.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00171
Author Contributions
§Miss J.-W. Chen and D.-W. Chen contributed equally to this
work.
Notes
The authors declare no competing financial interest.
4-(Ethylsulfonyl)-3-methyl-5-phenyl-1-tosyl-1H-pyrazole (4K).
The title compound was obtained as a white solid (128.7 mg,
64%). Mp 154−156 °C.
ACKNOWLEDGMENTS
■
1H NMR (400 MHz, CDCl3) δ 7.60−7.51 (m, 3H), 7.49−7.41 (m,
2H), 7.31−7.22 (m, 4H), 2.72 (q, J = 7.2 Hz, 2H), 2.53 (s, 3H), 2.44
(s, 3H), 1.14 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 151.8, 148.4, 146.6, 133.9, 130.60, 130.55, 130.0, 128.4, 127.7,
126.0, 120.8, 50.7, 21.6, 13.9, 6.9; HRMS (TOFMS) m/z [M + Na]+
calcd for C19H20N2O4S2Na: 427.0762; found: 427.0769.
This work was financially supported by the Natural Science
Foundation of Zhejiang Province of China (Grant No.
LQ20B020008), Cultivation project of Taizhou University,
and the Leading Innovative and Entrepreneur Team
Introduction Program of Zhejiang (No. 2019R01005).
3-Methyl-5-phenyl-1-tosyl-4-((trifluoromethyl)sulfonyl)-1H-pyra-
zole (4L). The title compound was obtained as a white solid (53.3 mg,
24%). Mp 139−142 °C.
DEDICATION
Dedicated to the cherished memory of Dr. Negish.
■
1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.4 Hz, 2H), 7.57 (t, J
= 7.6 Hz, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.22
(d, J = 7.6 Hz, 2H), 2.53 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 153.0, 152.7, 147.2, 133.2, 130.8, 130.22, 130.18,
128.8, 127.5, 124.8, 119.6 (q, J = 322.7 Hz), 113.1, 21.8, 13.5; HRMS
(TOFMS) m/z [M + Na]+ calcd for C18H15N2O4S2F3Na: 467.0323;
found: 467.0330.
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