The synthesis and biological activities of [5-(4-substituted phenylsulfinyl/sulfonyl)-1,3-dimethyl-1 H-pyrazol-4-Yl]-arylmethanones

Article abstract of DOI:10.1080/10426507.2013.829832

A novel series of pyrazole derivatives containing substituted phenylsulfinyl/sulfonyl group have been synthesized via the oxidation of intermediate pyrazole sulfoether with H₂O₂ in acetic acid. The novel compounds were characterized by melting point, ¹H NMR, FT-IR, MS, and elemental analysis or HRMS. The biological activity results showed that most of the title compounds exhibit significant fungicidal activities against Alternaria solani Sorauer, Phytophthora capsici, and Corynespora cassiicola. [Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]

Full text of DOI:10.1080/10426507.2013.829832

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The Synthesis and Biological Activities
of [5-(4-Substituted Phenylsulfinyl/
Sulfonyl)-1,3-Dimethyl-1H-Pyrazol-4-Yl]-
Arylmethanones
Bao-Lei Wang a , Qing-Nan Li a , Yi-Zhou Zhan a , Li-Xia Xiong a , Shu-
Jing Yu a & Zheng-Ming Li a
a State-Key Laboratory of Elemento-Organic Chemistry , Elemento-
Organic Chemistry Institute, Nankai University , Tianjin , China
Accepted author version posted online: 20 Aug 2013.Published
online: 12 Mar 2014.
To cite this article: Bao-Lei Wang , Qing-Nan Li , Yi-Zhou Zhan , Li-Xia Xiong , Shu-Jing Yu & Zheng-
Ming Li (2014) The Synthesis and Biological Activities of [5-(4-Substituted Phenylsulfinyl/Sulfonyl)-1,3-
Dimethyl-1H-Pyrazol-4-Yl]-Arylmethanones, Phosphorus, Sulfur, and Silicon and the Related Elements,
189:4, 483-491, DOI: 10.1080/10426507.2013.829832
To link to this article: http://dx.doi.org/10.1080/10426507.2013.829832
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Phosphorus, Sulfur, and Silicon, 189:483–491, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.829832
THE SYNTHESIS AND BIOLOGICAL ACTIVITIES OF
[5-(4-SUBSTITUTED PHENYLSULFINYL/SULFONYL)-1,3-
DIMETHYL-1H-PYRAZOL-4-YL]-ARYLMETHANONES
Bao-Lei Wang, Qing-Nan Li, Yi-Zhou Zhan, Li-Xia Xiong,
Shu-Jing Yu, and Zheng-Ming Li
State-Key Laboratory of Elemento-Organic Chemistry, Elemento-Organic
Chemistry Institute, Nankai University, Tianjin, China
GRAPHICAL ABSTRACT
O
CH3
R1
O
O
CH3
R1
R1
CH3
N
O
n
N
(1) POCl3
H2O2
S
N
N
S
R2
AcOH
(2) Arylthiol, NaH, THF
OH
N
CH3
N
R2
CH3
CH3
3a-3f
n = 1, 2
4a-4e
5a-5d
1
Abstract A novel series of pyrazole derivatives containing substituted phenylsulfinyl/sulfonyl
group have been synthesized via the oxidation of intermediate pyrazole sulfoether with H2O2
in acetic acid. The novel compounds were characterized by melting point, 1H NMR, FT-IR,
MS, and elemental analysis or HRMS. The biological activity results showed that most of
the title compounds exhibit significant fungicidal activities against Alternaria solani Sorauer,
Phytophthora capsici, and Corynespora cassiicola.
[Supplementary materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
files: Additional text and figures.]
Keywords Pyrazole; sulfoxide; sulfone; synthesis; biological activities
INTRODUCTION
Nitrogen linked heterocyclic compounds play very important roles because of their
versatile and useful biological properties in medicinal and pesticidal areas.1–10 It is well-
known that the study of pyrazole derivatives is significant in heterocyclic chemistry, and
Received 19 April 2013; accepted 22 July 2013.
This work was supported by the National Basic Research Program of China (No. 21372133), the National
Key Technologies Research and Development Program (2011BAE06B05-3), and the National Natural Science
Foundation of China (No. 21372133). We thank Dr. Yong-Hong Li of the Biological Assay Center, Nankai
University, for herbicidal tests of compounds.
Address correspondence to Bao-Lei Wang and Zheng-Ming Li, State-Key Laboratory of Elemento-Organic
Chemistry, Elemento-Organic Chemistry Institute, Nankai University, Tianjin 300071, China. E-mail: wang-
baolei@126.com, nkzml@vip.163.com
483

484
B.-L. WANG ET AL.
Scheme 1 The structures of commercial pesticides containing pyrazole ring.
some of the pyrazole derivatives have been widely used owing to their antibacterial,11
anticancer,12 antioxidant,13 anti-Alzheimer,14 herbicidal,15 insecticidal,16 and fungicidal
activities.17 There are many pesticides that include a pyrazole-heterocyclic structure; for
example, Pyrazoxyfen (as shown in Scheme 1), a kind of phenylethanone containing pyra-
zolyloxy moiety, is one of a class of bleaching herbicides that acts its activity through
inhibition of 4-hydroxyphenyl-pyruvate-dioxygenase.18 Pyrazole compounds, Penthiopy-
rad and Pyraclostrobin, have been found to have potential antifungal activities for the
control of some plant diseases.19 Chlorantraniliprole, a new insecticide with the anthranilic
diamide structure containing a N-pyridylpyrazole heterocycle, has been characterized by
its high levels of insecticidal activity and low toxicity to mammals attributed to a high
selectivity for insect over mammalian ryanodine receptors.20 With growing applications in-
volving their synthesis and bioactivity, chemists and biologists have directed considerable
attention to the research of pyrazole derivatives. In addition, it has been demonstrated that
the sulfoxide and sulfone groups are important pharmacophores of many pesticides, such
as Fipronil21 and KIH-485,22 and are often introduced into some bioactive heterocycles to
enhance the possible activities during the pesticide design.
It is known that the modification of the structural profile by the change of substituents
at the different positions in pyrazole ring may bring about significant change in bioactiv-
ity. Therefore, in continuation of our research on the synthesis of bioactive heterocyclic
compounds, a series of new pyrzole derivatives containing arylacyl and arylsulfinyl or aryl-
sulfonyl groups (at 4- and 5-position of the pyazole ring, respectively) were designed and
synthesized based on the structure of Pyrazoxyfen. These new structures were achieved
by the chlorination of hydroxylpyrazole, a key intermediate involving in the synthesis of
Pyrazoxyfen, followed by nucleophilic substitution of pyrazole chloride with substituted
thiophenols and oxidation of sulfoether (Scheme 2). Meanwhile, their herbicidal, insecti-
cidal, and fungicidal activities were investigated in this paper.
RESULTS AND DISCUSSION
Synthesis
Referring to the literature reported by DeWald et al.,23 intermediate 1a was prepared
successfully (yield 49%) in a one-pot method involving a Scotten-Baumann acylation
of 1,3-dimethyl-1H-pyrazol-5(4H)-one with 3-chlorobenzoyl chloride and then a Fries
rearrangement reaction of product ester catalyzed by Ca(OH)2 in dioxane at refluxing (2 h).
1b was obtained in a very low yield using this method, whereas it was synthesized with high
yield (65%) via a two-step method, in which the second step (Fries rearrangement) is at the

SYNTHESIS AND BIOACTIVITIES OF NOVEL PYRAZOLES
485
Scheme 2 The synthetic routes of the title compounds.
condition of K2CO3 as catalyst and dioxane as solvent, refluxing for 2–3 h.24 Intermediate
1 reacted with POCl3 to easily give intermediate 2.
The sulfoether compounds 3 can be synthesized from pyrazole chlorides 2 and
substituted thiophenols in THF using NaH as base at room temperature or reflux condition,
but the reaction cannot be completed. This may be due to the weakened reactivity of the
Cl atom caused by a p-π conjugative effect of pyrazole ring with Cl atom. The sulfoxide
compounds 4 were synthesized from the oxidation of sulfoethers with H2O2 in acetic acid
for 4∼6 h at 35–40◦C, but some amount of substrate sulfoethers existed in the products;
sulfone compounds 5 were obtained in same reaction system at 80–85◦C, likewise a small
amount of substrate sulfoxides also existed in the products. These experimental results
indicate that the oxidation is not complete under these conditions. This probably originated
from the electronic effect of substituents on the structures of these compounds such as the
4-arylacyl, or 5-arylthio, or 5-arylsulfinyl group on the pyrazole ring, and from the existence
of steric hindrance that two bulky aryl groups (pyrazole and benzene rings) locating on
same sulfur atom. So the pure sulfoxides 4 and sulfones 5 were obtained via column
chromatography.
Infrared Spectra
The infrared spectrum of title compounds 4 and 5 showed absorption band at
1633∼1671 cm−1 for C O stretching. The characteristic stretching vibrations ν (S O)
and ν (O S O) around at 1047∼1060 and 1157–1172 cm−1, respectively.

486
B.-L. WANG ET AL.
1H NMR Spectra
In the 1H NMR spectra of 3, the NCH3 proton signals of sulfoether were observed at δ
3.75–3.93 ppm; sulfoxide were observed at δ 3.88–3.96 ppm and δ 4.07–4.12 ppm as sulfone
respectively—this is due to the influences of electron withdrawing group of sulfoxide and
sulfone (deshielding effect). Another set of CH3 proton signals in the pyrazole ring of
compounds 3, 4 and 5 were observed at δ 1.92–2.61 ppm, and the sequence of the chemical
shift values for these signals was sulfone > sulfoxide > sulfoether, with same substituents
or groups each other, which can be ascribed to the same reason of deshielding effect. The
other peaks observed were the aromatic protons at δ 6.78–8.03 ppm and an additional
doublet at δ 1.19∼1.36 ppm and multiplet at δ 2.82–3.05 ppm in compounds 3c, 3f, 4c, 4e,
5c, and 5d respectively due to –CH(CH3)2 group attached to phenyl ring.
Mass Spectra
The ESI-MS of title compounds 4 and 5 showed a molecular ion peak of [M+H]+
clearly. To further investigate the cleavage rule of title compounds, 5b, as a representative
compound, was selected and determined for mass spectra by an electron impact ion source.
Figure S1 (Supplemental Materials) illustrated the proposed mass fragmentation pattern
of compound 5b, in which the typical peaks at m/z 343 (100%) and 344 (78.2%) were
produced by the loss of •SO2H and SO2 fragments from molecular ion, respectively.
Biological Activities
The herbicidal activity of the title compounds was bioassayed in the glasshouse on
four herbs representative of monocotyledonous and dicotyledonous plants (Echinochloa
crus-galli, Digitaria adscendens, and Brassica campestris, Amaranthus retroflexus), and
the results are listed in Table S1 (Supplemental Materials). At a dosage of 1500 g/ha,
compound 4a possessed 40% and 22.1% inhibitory activities against Brassica campestris
and Amaranthus retroflexus, respectively, in postemergence test; compounds 4d and 5a
exhibited 43.2% and 34.7% inhibition of the growth of Amaranthus retroflexus stems and
leaves. Other compounds showed very weak herbicidal activities under same test conditions.
The larvicidal activity of the title compounds against oriental armyworm (Mythimna
separate Walker) is summarized in Table S2 (Supplemental Materials). Among these com-
pounds, 4b, 4d, and 5d possessed moderate activity at 200 μg/mL with death rates of 40%,
40%, and 30%, respectively.
The in vitro fungicidal results of compounds against six fungi are listed in same Table
S2. It was found that most of the title compounds exhibited obvious growth inhibitory
activities against all test fungi, especially some showed significant fungicidal activities
against Alternaria solani Sorauer, Phytophthora capsici, and Corynespora cassiicola at
50 μg/mL, such as compounds 4b, 4c, and 4a.
EXPERIMENTAL
Melting points were determined using a Taike X-4 apparatus and were uncorrected.
1
Infrared spectra were recorded on a Nicolet 570 spectrophotometer as KBr tablets. H
NMR spectra were measured on a Bruker AV-400 instrument (400 MHz) using TMS as
an internal standard and CDCl3 as solvent. HRMS data was obtained on a FTICR-MS

SYNTHESIS AND BIOACTIVITIES OF NOVEL PYRAZOLES
487
instrument (Ionspec 7.0T). Mass spectra were recorded on a HP-1100 LC/MS instrument
and a Thermo Finigan LCQ Advantage instrument. Elemental analyses were performed on
a Yanaco MT-3CHN elemental analyzer.
Synthesis of the Intermediate Hydroxylpyrazole (1a, 1b). (3-Chlorophenyl)
(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone (1a) was synthesized according to
Ref. 23; (2,4-dichlorophenyl)(5-hydroxy-1,3-dimethyl-1H-pyrazol-4-yl)methanone (1b)
was synthesized according to the literature.24
Synthesis of the Intermediate Pyrazole Chloride (2a, 2b). A mixture of
POCl3 (9.25 g, 0.06 mol) and intermediate 1 (0.03 mol) was stirred at reflux for 6 h. After
cooling, the reaction solution was poured into a mixture of CH2Cl2 (25 mL), ice (20 g) and
25% ammonium hydroxide (20 mL) with stirring, then the organic layer was separated,
the aqueous layer was further extracted with CH2Cl2 (3 × 15 mL). The organic layer
was combined, washed with brine and dried over anhydrous Na2SO4. The solvent was
evaporated to give a residue, which was recrystallized in hexane to afford intermediate 2.
(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)(3-chlorophenyl)methanone
(2a):
white crystal, yield 93%, m.p. 81–83◦C (Lit.25 m.p. 81–83◦C); H NMR(400 MHz,
CDCl3): 2.30 (s, CH3, 3H), 3.84 (s, NCH3, 3H), 7.40 (t, J = 8.0 Hz, Ph-H, 1H), 7.54 (d,
J = 8.0 Hz, Ph-H, 1H), 7.59 (d, J = 8.0 Hz, Ph-H, 1H), and 7.69 (s, Ph-H, 1H).
(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)(2,4-dichlorophenyl)methanone (2b):
white crystal, yield 71.6%, m.p. 98–99◦C; 1H NMR(400 MHz, CDCl3): 2.37 (s, CH3, 3H),
3.79 (s, NCH3, 3H), 7.25 (d, J = 8.0 Hz, Ph-H, 1H), 7.34 (d, J = 8.0 Hz, Ph-H, 1H), and
7.44 (s, Ph-H, 1H).
1
Synthesis of the Intermediate Pyrazole Sulfoether (3a–3f). To a mixture
of NaH (50%, 6 mmol) in THF (10 mL) was added dropwise a solution of substituted
thiophenol (4 mmol) in THF (5 mL) at 0◦C. After being stirred at room temperature for
2∼4 h, the mixture was then added dropwise a solution of intermediate 2 (4 mmol) in THF
(10 mL). The mixture was further stirred at room temperature for 24 h, then added water
(25 mL) and extracted with ethyl acetate (3 × 15 mL). The organic layer was combined,
dried over anhydrous Na2SO4. The solvent was evaporated in vacuo and the residue was
purified by silica-gel column eluted with ethyl acetate/petroleum ether (1:7) to give a light
yellow sticky product.
(3-Chlorophenyl)(1,3-dimethyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone
(3a): yield 73%; 1H NMR(400 MHz, CDCl3): 2.28 (s, CH3, 3H), 3.75 (s, NCH3, 3H), 6.86
(d, J = 8.0 Hz, Ph-H, 2H), 7.10–7.24 (m, Ph-H, 4H), 7.42 (d, J = 8.0 Hz, Ph-H, 1H),
7.47 (d, J = 8.0 Hz, Ph-H, 1H), and 7.55 (s, Ph-H, 1H); ESI-FTMS for C18H15ClN2OS
[M+H]+: Calcd. 343.0672, Found 343.0668.
(3-Chlorophenyl)(5-(4-chlorophenylthio)-1,3-dimethyl-1H-pyrazol-4-
yl)methanone (3b): yield 49%; 1H NMR(400 MHz, CDCl3): 2.32 (s, CH3, 3H),
3.82 (s, NCH3, 3H), 6.87 (d, J = 8.4 Hz, Ph-H, 2H), 7.19 (d, J = 8.4 Hz, Ph-H, 2H), 7.32
(t, J = 8.0 Hz, Ph-H, 1H), 7.49 (d, J = 8.0 Hz, Ph-H, 1H), 7.53 (d, J = 8.0 Hz, Ph-H,
1H), and 7.60 (s, Ph-H, 1H); ESI-FTMS for C18H14Cl2N2OS [M+H]+: Calcd. 377.0282,
Found 377.0275.
(3-Chlorophenyl)(5-(4-isopropylphenylthio)-1,3-dimethyl-1H-pyrazol-4-
1
yl)methanone (3c): yield 51%; H NMR(400 MHz, CDCl3): 1.19 (d, J = 6.8 Hz,
CH(CH3)2, 6H), 2.33 (s, CH3, 3H), 2.82 (m, CH(CH3)2, 1H), 3.82 (s, NCH3, 3H), 6.85 (d,
J = 8.0 Hz, Ph-H, 2H), 7.06 (d, J = 8.0 Hz, Ph-H, 2H), 7.30 (t, J = 8.0 Hz, Ph-H, 1H),
7.48 (d, J = 8.0 Hz, Ph-H, 1H), 7.52 (d, J = 8.0 Hz, Ph-H, 1H), and 7.58 (s, Ph-H, 1H);
ESI-FTMS for C21H21ClN2OS [M+H]+: Calcd. 385.1141, Found 385.1140.

488
B.-L. WANG ET AL.
(2,4-Dichlorophenyl)(1,3-dimethyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone
(3d): yield 60%; 1H NMR(400 MHz, CDCl3): 2.46 (s, CH3, 3H), 3.77 (s, NCH3, 3H), 6.82
(d, J = 7.2 Hz, Ph-H, 2H), and 7.06–7.35 (m, Ph-H, 6H); ESI-FTMS for C18H14Cl2N2OS
[M+H]+: Calcd. 377.0282, Found 377.0286.
(5-(4-Chlorophenylthio)-1,3-dimethyl-1H-pyrazol-4-yl)(2,4-dichlorophenyl)
1
methanone (3e): yield 32%; H NMR(400 MHz, CDCl3): 2.43 (s, CH3, 3H), 3.79 (s,
NCH3, 3H), 6.78 (d, J = 8.4 Hz, Ph-H, 2H), 7.10–7.20 (m, Ph-H, 4H), and 7.33 (s, Ph-H,
1H); ESI-FTMS for C18H13Cl3N2OS [M+H]+: Calcd. 410.9892, Found 410.9899.
(2,4-Dichlorophenyl)(5-(4-isopropylphenylthio)-1,3-dimethyl-1H-pyrazol-4-
1
yl)methanone (3f): yield 58%; H NMR(400 MHz, CDCl3): 1.36 (d, J = 6.8 Hz,
CH(CH3)2, 6H), 2.61 (s, CH3, 3H), 3.00 (m, CH(CH3)2, 1H), 3.93 (s, NCH3, 3H), 6.93 (d,
J = 8.4 Hz, Ph-H, 2H), 7.21–7.26 (m, Ph-H, 4H), and 7.46 (s, Ph-H, 1H); ESI-FTMS for
C21H20Cl2N2OS [M+H]+: Calcd. 419.0752, Found 419.0746.
Synthesis of [5-(4-substituted phenylsulfinyl)-1,3-dimethyl-1H-
pyrazol-4-yl]-arylmethanones (4a–4e)
To a stirred solution of 3 (1 mmol) in glacial acetic acid (10 mL), solution of
H2O2 (30%, 4 mmol) was dropwised. Reaction mixture was then stirred at 35–40◦C with
monitoring by TLC (about 4∼6 h) and poured into H2O, then adjusted pH value 7∼8 by
NaHCO3 solution. The mixture was extracted with ethyl acetate (3 × 15 mL). The organic
layer was combined, dried over anhydrous Na2SO4. The solvent was removed and the
residue was purified by silica-gel column eluted with ethyl acetate/petroleum ether (1:7) to
give the product 4.
5-Phenylsulfinyl-1,3-dimethyl-1H-pyrazol-4-yl-(3-chlorophenyl)methanone
(4a): white crystal, yield 89%, m.p. 126–128◦C; IR(υ, cm−1): 3051(m, Ph-H), 2936(m,
CH3), 1642(vs, C O), 1591, 1581, 1497, 1459(s, Ar), 1047(vs, S O); 1H NMR(400 MHz,
CDCl3): 2.10 (s, CH3, 3H), 3.88 (s, NCH3, 3H), 7.45–7.56 (m, Ph-H, 4H), 7.60 (d, J =
8.0 Hz, Ph-H, 1H), 7.69 (d, J = 8.0 Hz, Ph-H, 1H), and 7.83 (t, J = 7.2 Hz, Ph-H, 3H);
ESI-MS: 359 ([M+H]+); Elem. Anal. for C18H15ClN2O2S: Calcd. C 60.25, H 4.21, N,
7.81; Found C 60.35, H 4.12, N 7.70.
[5-(4-Chlorophenylsulfinyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(3-chlorophenyl)
methanone (4b): white crystal, yield 62%, m.p. 110–112◦C; IR(υ, cm−1): 3059(m, Ph-H),
1
2953 (m, CH3), 1635(vs, C O), 1590, 1569, 1495, 1465(s, Ar), 1055(vs, S O); H
NMR(400 MHz, CDCl3): 2.08 (s, CH3, 3H), 3.90 (s, NCH3, 3H), 7.47 (t, J = 8.0 Hz,
Ph-H, 1H), 7.51 (d, J = 8.4 Hz, Ph-H, 2H), 7.61 (d, J = 8.0 Hz, Ph-H, 1H), 7.68 (d, J =
8.0 Hz, Ph-H, 1H), 7.80 (s, Ph-H, 1H), and 7.83 (d, J = 8.4 Hz, Ph-H, 2H); ESI-MS: 393
([M+H]+); ESI-FTMS for C18H14Cl2N2O2S [M+H]+: Calcd. 393.0226, Found 393.0226.
[5-(4-Isopropylphenylsulfinyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(3-chlorophenyl)
methanone (4c): white crystal, yield 97%, m.p. 85–87◦C; IR(υ, cm−1): 3060(s, Ph-H),
2960, 2850(m, CH, CH3), 1644(vs, C O), 1592, 1569, 1496, 1461(s, Ar), 1055(vs, S O);
1H NMR(400 MHz, CDCl3): 1.26 (d, J = 6.8 Hz, CH(CH3)2, 6H), 2.09 (s, CH3, 3H), 2.96
(m, CH(CH3)2, 1H), 3.91 (s, NCH3, 3H), 7.37 (d, J = 8.4 Hz, Ph-H, 2H), 7.46 (t, J =
8.0 Hz, Ph-H, 1H), 7.59 (d, J = 8.0 Hz, Ph-H, 1H), 7.68 (d, J = 8.0 Hz, Ph-H, 1H), 7.73
(d, J = 8.4 Hz, Ph-H, 2H), and 7.79 (s, Ph-H, 1H); ESI-MS: 401 ([M+H]+); ESI-FTMS
for C21H21ClN2O2S [M+H]+: Calcd. 401.1085, Found 401.1084.
[5-(4-Chlorophenylsulfinyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(2,4-dichlorophenyl)
methanone (4d): white crystal, yield 33%, m.p. 131–133◦C; IR(υ, cm−1): 3085(m, Ph-H),

SYNTHESIS AND BIOACTIVITIES OF NOVEL PYRAZOLES
489
1
2947(m, CH3), 1633(vs, C O), 1586, 1554, 1498, 1472(s, Ar), 1054(vs, S O); H
NMR(300 MHz, CDCl3): 1.92 (s, CH3, 3H), 3.95 (s, NCH3, 3H), 7.39–7.52 (m, Ph-H,
5H), and 7.81 (d, J = 8.7 Hz, Ph-H, 2H); ESI-MS: 427 ([M+H]+); ESI-FTMS for
C18H13Cl3N2O2S [M+Na]+: Calcd. 448.9656, Found 448.9654.
[5-(4-Isopropylphenylsulfinyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(2,4-dichlorophe
nyl)methanone (4e): white crystal, yield 49%, m.p. 110–112◦C; IR(υ, cm−1): 3092(m,
Ph-H), 2958, 2868(m, CH, CH3), 1643(vs, C O), 1590, 1556, 1496, 1459(s, Ar), 1060(vs,
1
S O); H NMR(400 MHz, CDCl3): 1.25 (d, J = 6.4 Hz, CH(CH3)2, 6H), 1.96 (s, CH3,
3H), 2.95 (m, CH(CH3)2, 1H), 3.96 (s, NCH3, 3H), 7.37 (d, J = 7.6 Hz, Ph-H, 2H), 7.38
(s, Ph-H, 2H), 7.48 (s, Ph-H, 1H), and 7.71 (d, J = 7.6 Hz, Ph-H, 2H); ESI-MS: 435
([M+H]+); Elem. Anal. for C21H20Cl2N2O2S: Calcd. C 57.93, H 4.63, N, 6.43; Found C
57.31, H 4.88, N 6.44.
Synthesis of [5-(4-substituted phenylsulfonyl)-1,3-dimethyl-1H-pyrazol-
4-yl]-arylmethanones (5a–5d). The synthetic and purified procedures were similar to
those of compound 4, in addition to a reaction temperature of 80–85◦C.
5-Phenylsulfonyl-1,3-dimethyl-1H-pyrazol-4-yl-(3-chlorophenyl)methanone
(5a): white crystal, yield 72%, m.p. 118–119◦C; IR(υ, cm−1): 3059(s, Ph-H), 2929(m,
1
CH3), 1668(vs, C O), 1589, 1571, 1522, 1465(s, Ar),1329, 1172(vs, O S O); H
NMR(400 MHz, CDCl3): 2.06 (s, CH3, 3H), 4.07 (s, NCH3, 3H), 7.44 (t, J = 8.0 Hz,
Ph-H, 1H), 7.56–7.74 (m, Ph-H, 5H), 7.83 (s, Ph-H, 1H), and 8.03 (d, J = 8.0 Hz, Ph-H,
2H); ESI-MS: 375 ([M+H]+); Elem. Anal. for C18H15ClN2O3S: Calcd. C 57.68, H 4.03,
N, 7.47; Found C 57.52, H 3.92, N 7.30.
[5-(4-Chlorophenylsulfonyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(3-chlorophenyl)
methanone (5b): white crystal, yield 81%, m.p. 137–139◦C; IR(υ, cm−1): 3087(s, Ph-H),
2931(m, CH3), 1656(vs, C O), 1589, 1569, 1510, 1476(s, Ar),1329, 1172(vs, O
S
O);
1H NMR(400 MHz, CDCl3): 2.05 (s, CH3, 3H), 4.08 (s, NCH3, 3H), 7.44 (t, J = 8.0 Hz,
Ph-H, 1H), 7.55 (d, J = 8.4 Hz, Ph-H, 2H), 7.60 (d, J = 7.6 Hz, Ph-H, 1H), 7.72 (d, J
= 7.6 Hz, Ph-H, 1H), 7.82 (s, Ph-H, 1H), 7.99 (d, J = 8.4 Hz, Ph-H, 2H); ESI-MS: 409
([M+H]+), 839 ([2M+Na]+); EI-MS: 408 (M+, 17.5%), 407 (20.1%), 344 (78.2%), 343
(100%), 309 (63.8%), 297 (82.4%), 233 (22.5%), 139 (25.4%), and 111 (56.8%); Elem.
Anal. for C18H14Cl2N2O3S: Calcd. C 52.82, H 3.45, N, 6.84; Found C 52.73, H 3.48, N
6.71.
[5-(4-Isopropylphenylsulfonyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(3-chlorophenyl)
methanone (5c): white crystal, yield 90%, m.p. 98–100◦C; IR(υ, cm−1): 3074(s, Ph-H),
2962, 2874(m, CH, CH3), 1664(vs, C O), 1595, 1571, 1514, 1464(s, Ar), 1332, 1172(vs,
1
O S O); H NMR(400 MHz, CDCl3): 1.26 (d, J = 7.2 Hz, CH(CH3)2, 6H), 2.06 (s,
CH3, 3H), 2.99 (m, CH(CH3)2, 1H), 4.08(s, NCH3, 3H), 7.40 (d, J = 8.4 Hz, Ph-H, 2H),
7.43 (t, J = 8.0 Hz, Ph-H, 1H), 7.58 (d, J = 8.0 Hz, Ph-H, 1H), 7.73(d, J = 8.0 Hz, Ph-H,
1H) 7.82 (s, Ph-H, 1H), and 7.91(d, J = 8.4 Hz, Ph-H, 2H); ESI-MS: 417 ([M+H]+),
855 ([2M+Na]+); ESI-FTMS for C21H21ClN2O3S [M+H]+: Calcd. 417.1034, Found
417.1035.
[5-(4-Isopropylphenylsulfonyl)-1,3-dimethyl-1H-pyrazol-4-yl]-(2,4-dichlorophe
nyl)methanone (5d): white crystal, yield 41%, m.p. 112–114◦C; IR(υ, cm−1): 3071(s,
Ph-H), 2964, 2875(m, CH, CH3), 1671(vs, C O), 1584, 1553, 1499, 1465(s, Ar), 1334,
1
1157(vs, O S O); H NMR(400 MHz, CDCl3): 1.28 (d, J = 7.2 Hz, CH(CH3)2, 6H),
2.02 (s, CH3, 3H), 3.05 (m, CH(CH3)2, 1H), 4.12(s, NCH3, 3H), 7.28–7.56 (m, Ph-H,
5H), and 7.89(d, J = 8.1 Hz, Ph-H, 2H); ESI-MS: 451 ([M+H]+); ESI-FTMS for
C21H20Cl2N2O3S [M+Na]+: Calcd. 473.0464, Found 473.0471.

490
B.-L. WANG ET AL.
Herbicidal Activity Tests
The herbicidal activity tests for Pre-emergence and Post-emergence were performed
in the greenhouse according to the literature methods.26,27
Insecticidal Activity Test
Insecticidal activity against oriental armyworm (Mythimna separate Walker) was
performed in the greenhouse.16
Fungicidal Activity Tests
Fungicidal activities of compounds against six plant fungi (Table S2) were evaluated
using the mycelium growth rate test.28,29
CONCLUSION
A novel series of [5-(4-substituted phenylsulfinyl/sulfonyl)-1,3-dimethyl-1H-
pyrazol-4-yl]-arylmethanones have been synthesized successfully via the oxidation of
intermediate pyrazole sulfoether with H2O2 in acetic acid and characterized by melting
point, elemental analysis, and organic spectroscopy. The biological activity results showed
that most of the title compounds exhibit significant fungicidal activities against Alternaria
solani Sorauer, Phytophthora capsici, and Corynespora cassiicola.
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