Synthesis, crystal structure, and fungicidal activity of novel 1,5-diaryl-1H-pyrazol-3-Oxy derivatives containing oxyacetic acid or oxy(2-thioxothiazolidin-3-yl)ethanone moieties

Article abstract of DOI:10.1002/jhet.1045

A series of novel 1,5-diaryl-1H-pyrazol-3-oxy derivatives containing oxyacetic acid or oxy(2-thioxothiazolidin-3-yl)ethanone moieties were prepared from methyl 3-arylacrylates via a serial of reactions included addition-cyclization, oxidation, substitution, hydrolysis, and condensation. Their structures were confirmed by ¹H-NMR, ¹³C-NMR, IR, and elemental analysis. In addition, the crystal structure of the compound 2-(1,5-diphenyl-1H-pyrazol-3-yloxy)-1-(2-thioxothiazolidin-3-yl)ethanone was determined by single crystal X-ray diffraction analysis. Bioassay results indicated that the compound 2-(5-(4-chlorophenyl)-1-phenyl-1H-pyrazol-3-yloxy)- 1-(2-thioxo-thiazolidin-3-yl)ethanone exhibited moderate inhibitory activity against Gibberella zeae at the dosage of 10 μg mL^-1.

Full text of DOI:10.1002/jhet.1045

1370
Synthesis, Crystal Structure, and Fungicidal Activity of Novel
1,5‐Diaryl‐1H‐Pyrazol‐3‐Oxy Derivatives Containing Oxyacetic
Acid or Oxy(2‐thioxothiazolidin‐3‐yl)ethanone Moieties
Vol 49
*
Yuanyuan Liu, Guangke He, Chen Kai, Yufeng Li, and Hongjun Zhu
Department of Applied Chemistry, College of Science, Nanjing University of Technology,
Nanjing 210009, People’s Republic of China
*
E-mail: zhuhjnjut@hotmail.com
Received March 11, 2011
DOI 10.1002/jhet.1045
View this article online at wileyonlinelibrary.com.
A series of novel 1,5‐diaryl‐1H‐pyrazol‐3‐oxy derivatives containing oxyacetic acid or oxy(2‐thioxothia-
zolidin‐3‐yl)ethanone moieties were prepared from methyl 3‐arylacrylates via a serial of reactions included
addition‐cyclization, oxidation, substitution, hydrolysis, and condensation. Their structures were confirmed
by 1H‐NMR, 13C‐NMR, IR, and elemental analysis. In addition, the crystal structure of the compound
2‐(1,5‐diphenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxothiazolidin‐3‐yl)ethanone was determined by single crystal
X‐ray diffraction analysis. Bioassay results indicated that the compound 2‐(5‐(4‐chlorophenyl)‐1‐phenyl‐
1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxo‐thiazolidin‐3‐yl)ethanone exhibited moderate inhibitory activity against
Gibberella zeae at the dosage of 10 μg mL−1
.
J. Heterocyclic Chem., 49, 1370 (2012).
INTRODUCTION
as an important skeleton in exploring novel bioactive mole-
cules. Motivated by the aforementioned findings, we con-
ceived that replacement of the active hydrogen of the
thiazolidine‐2‐thione with an oxyacetic acid group forming
an oxy(2‐thioxothiazo‐lidin‐3‐yl)ethanone moiety and then
incorporating with 1H‐pyrazol‐3‐oxy derivatives might
result in new compounds with good biological activities.
Two common methods are known at present for the
synthesis of these oxy(2‐thioxothiazolidin‐3‐yl)ethanone
compounds. One involves the following two steps: oxyace-
tyl chlorides were first prepared by the reaction of oxyacetic
acids with thionyl chloride, which further proceeded dehy-
drochlorination with thiazolidine‐2‐thione [16–18]. The
other involves the condensation of thiazolidine‐2‐thione with
oxyacetic acids, using N,N′‐dicyclohexylcarbodiimide
(DCC) as dehydrating agent [19, 20] and 4‐(dimethyla-
mino)pyridine (DMAP) as catalyst. In contrast to thionyl
chloride, DCC is an environmentally friendly and conve-
nient reagent for the synthesis of heterocyclic acylamide
compounds. Therefore, in this article, we report the synthesis
of a series of novel 1,5‐diaryl‐1H‐pyrazol‐3‐oxy derivatives
containing oxy(2‐thioxothiazolidin‐3‐yl)ethanone moiety
(6a–6e) through the DCC condensation of thiazolidine‐2‐
thione with 2‐(1,5‐diaryl‐1H‐pyrazol‐3‐yloxy)acetic acids
(5a–5e), and the crystal structure of the compound 2‐(1,5‐
diphenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxothiazolidin‐3‐yl)‐
ethanone (6a). Meanwhile the fungicidal activity of the
As the discovery of the strobilurin fungicide pyraclostrobin
by Baden Aniline and Soda Factory (BASF) scientists, 1H‐
pyrazol‐3‐oxy derivatives have attracted considerable atten-
tion in chemical and medicinal research because of their low
mammalian toxicity and diverse bioactivities such as fungi-
cidal [1–3], insecticidal [4], herbicidal [5], and plant growth
regulatory activities [6]. Furthermore, several biological stud-
ies have also pointed out the value of alkyloxyacetate [7] and
oxyacetic acid [8] as bioactive groups. Recently, focusing on
incorporating alkyloxyacetate group with 1H‐pyrazol‐3‐oxy
derivatives in the hope of obtaining compounds of potential
bioactivities, we reported the synthesis of novel 1,5‐diaryl‐
1H‐pyrazol‐3‐oxyacetates‐containing alkyloxyacetate moiety
and their good fungicidal activity [9]. However, very few repre-
sentatives of bioactive 1,5‐diaryl‐1H‐pyrazol‐3‐oxyacetic acids
have hitherto been described in the literature.
On the other hand, increasing attention has been devoted
to the thiazole‐based derivatives since the unique thiazole
unit has been found in numerous pesticides such as thiflu-
zamide [10], ethaboxam [11], and thiamethoxam [12].
Thiazolidine‐2‐thione, an excellent representative of thia-
zole derivatives, plays a significant role. Biological studies
of the thiazolidine‐2‐thione have been shown to possess a
variety of biological activities [13–15]. Therefore, we have
reason to believe that the thiazolidine‐2‐thione can be used
© 2012 HeteroCorporation

November 2012 Synthesis, Crystal Structure, and Fungicidal Activity of Novel 1,5‐Diaryl‐1H‐pyrazol‐3‐oxy
Derivatives Containing Oxyacetic Acid or Oxy(2‐thioxothiazolidin‐3‐yl)ethanone Moieties
1371
Scheme 1
compounds 4a–4e, 5a–5e, and 6a–6e has been investigated
with the aim of understanding the structure‐activity relation-
ships and developing new fungicides. A preliminary in vitro
bioassay indicated that some of these newly synthesized
compounds displayed fungicidal activity at the dosage of
10 μg mL−1.
obtained when the reactions were first stirred at 0°C for 3 h
and then at room temperature for 12 h. The crude solids were
purified via flash chromatography to furnish good yield of
the desired products 2‐(1,5‐diaryl‐1H‐pyrazol‐3‐yloxy)‐1‐
(2‐thioxothiazolidin‐3‐yl)ethanones (6a–6e) (Scheme 3).
The structures of all synthesized compounds were con-
firmed by 1H‐NMR. Because of the difference of shielding
effect between carboxyl and carbonyl‐heteroaryl group, for
compounds 5a–5e and 6a–6e, the chemical shift of the
CH2 in the oxy side chain appears at δ 4.74–4.92 ppm
and δ 5.70–5.72 ppm, respectively, and the CH of the pyr-
azole ring appears at δ 6.04–6.24 ppm and δ 5.98–6.06
ppm, respectively. All these compounds showed a multi-
plet of aromatic protons in the range of δ 6.80–7.49 ppm.
A single peak appearing at the lowest field of δ 9.48–
RESULTS AND DISCUSSION
The key intermediates ethyl 2‐(1,5‐diaryl‐1H‐pyrazol‐3‐
yloxy)acetates (4a–4e) were prepared according to the
reported method from methyl 3‐arylacrylates (1a–1e)
via three steps including addition–cyclization, oxidation,
and substitution (Scheme 1) [9]. Thiazolidine‐2‐thione
(Scheme 2) was synthesized from 2‐aminoethanol through
two steps according to the reported procedure [21].
A previous report by Baraldi et al. described that alkaline
hydrolysis of oxypyrazolecarboxylic acid esters in a mixture
of methanol and sodium hydroxide solution could give
the corresponding carboxylic acids [22]. Motivated by this
finding, in our procedure, the hydrolysis of ethyl 2‐(1,5‐
diaryl‐1H‐pyrazol‐3‐yloxy)acetates (4a–4e) was carried out
in 95% ethanol in the presence of sodium hydroxide until
the starting material was completely consumed as judged
by thin‐layer chromatography (TLC) (Scheme 3). The target
products 2‐(1,5‐diaryl‐1H‐pyrazol‐3‐yloxy)acetic acids
(5a–5e) were obtained by acidification with hydrochloric
acid in moderate yield.
1
12.92 ppm in the H‐NMR showed that the target com-
pounds 5a–5e have carboxyl hydrogen. For compounds
6a–6e, the chemical shifts of the two CH2 in thiazolidine‐
2‐thione moiety appear at δ 4.60 ppm and δ 3.37 ppm, re-
spectively. In addition, the results of single crystal X‐ray
diffraction analysis of 2‐(1,5‐diphenyl‐1H‐pyrazol‐3‐
yloxy)‐1‐(2‐thioxothiazolidin‐3‐yl)ethanone (6a) further
validated the structure of the title compounds. Suitable
crystals of 6a were obtained by slow evaporation of ethyl
acetate solutions at room temperature for about 10 days.
Compound 6a crystallizes in the monoclinic space group
P21/c with unit cell parameters: a = 12.813(3) Å, b =
16.453(3) Å, c = 8.9470(18) Å, β = 97.68(3)°, Z = 4, Dc =
1.405 Mg m−3, μ = 0.306 mm–1, F(000) = 824. The detailed
crystal data and structure refinement of 6a are listed in
Table 1. The molecular structure and the higher occupancy
in the three‐dimensional packing arrangement are shown in
The DCC condensation of 2‐(1,5‐diaryl‐1H‐pyrazol‐3‐
yloxy)acetic acids (5a–5e) with thiazolidine‐2‐thione was
carried out in a molar ratio 1:1 in CH2Cl2 as solvent, using
DMAP as catalyst according to a similar method [19], and
was monitored by TLC. The most satisfactory results were
Scheme 2
Journal of Heterocyclic Chemistry
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Y. Liu, G. He, C. Kai, Y. Li, and H. Zhu
Vol 49
Scheme 3
Figures 1 and 2. The bond length of N1-C4 [1.408(5) Å] is
longer than normal N-C amide bond (1.325–1.352 Å) [23].
The C‐linked benzene ring A (C9‐C14), N‐linked benzene
ring B (C15‐C20), and thiazolidine‐2‐thione ring (N1/S1/
C1‐C3) are twisted 31.33°, 62.87°, and 82.71° from the
plane of the bridge 1H‐pyrazol ring (N2/N3/C6‐C8), re-
spectively. Rings A and B are, of course, planar and the
dihedral angle between them is 72.16°. The intramolecular
C-H…S hydrogen bond result in the formation of one
nonplanar pseudoring (C5/H5B/S2/C3/N1/C4), in which it
may be effective in the stabilization of the structure.
The compounds 4a–4e, 5a–5e, and 6a–6e were screened
for activity against two fungi, namely Gibberella zeae and
Rhizoctonia cerealis, at a concentration of 10 μg mL−1
according to a reported method [9, 24]. As a result, in
Table 2, most of the compounds have weak fungicidal
activity. Among these compounds, only compound 6d, in
which X is Cl group at the 4‐position on the phenyl ring,
exhibited moderate inhibitory activity against Gibberella
zeae. This might imply that the introduction of oxy(2‐
thioxothiazolidin‐3‐yl)ethanone group to the 1H‐pyrazol‐
3‐oxy was important for improving its fungicidal activity.
In terms of the 3‐substituent, molecular structure contain-
ing an oxy(2‐thioxothiazolidin‐3‐yl)ethanone moiety
seems to have somewhat higher fungicidal activity. The se-
quence of fungicidal activity against Gibberella zeae is oxy
(2‐thioxothiazolidin‐3‐yl)ethanone moiety > alkyloxyace-
tate moiety > oxyacetic acid moiety. For example, com-
pound 6d showed better activity than 4d and 5d. In terms
of the substituents X, compounds with electron‐withdrawing
substituents on the phenyl ring displayed higher fungicidal
activity against Gibberella zeae than that with electron‐
donating substituents, as seen in the comparison of the com-
pounds 4d–6d (X = 4‐Cl) and 4b–6b (X = 4‐OCH3) with X
at the 4‐position on the phenyl ring, 4c–6c (X = 3‐F) and
4e–6e (X = 3‐Cl) with X at the 3‐position on the phenyl ring.
Moreover, according to the different position and electronic
effect of the electron‐withdrawing substituents on the phenyl
ring, the sequence of fungicidal activity against Gibberella
zeae is para‐substituted > meta‐substituted and fluoro‐
substituted > chloro‐substituted. For example, within the
series of X = ‐Cl derivatives, para‐substituted 4d–6d showed
higher fungicidal activity than the corresponding meta‐
substituted 4e–6e and 4c–6c, while the fluoro‐substituted
4c–6c displayed better activity than the chloro‐substituted
4e–6e. However, most compounds showed no fungicidal
activity against Rhizoctonia cerealis except the compounds
4a, 4c, and 4d with weak activity.
Table 1
Crystal data and structure refinement for 6a.
Empirical formula
CCDC No.
C
20H17N3O2S2
823885
Formula weight
Temperature
395.49
293(2)
Wavelength
0.71073 Å
Crystal system, space group
Unit cell dimensions
Monoclinic, P21/c (No. 14)
a = 12.813(3) Å α = 90.00°
b = 16.453(3) Å β = 97.68(3)°
c = 8.9470(18) Å γ = 90.00°
1869.2(7) Å3
Volume
Z, Calculated density
Absorption coefficient
F(000)
4, 1.405 Mg m−3
0.306 mm–1
824
Crystal size
Theta range for data
collection
0.10 × 0.20 × 0.30 mm
1.60° to 25.27°
Limiting indices
–15 <= h <= 15, –19 <= k <= 0, 0
<= l <= 10
Reflections collected/unique
Max. and min. transmission
Refinement method
Data/restraints/parameters
Final R indices [I > 2σ (I)]
Largest diff. peak and hole
3625/3391 [Rint = 0.024]
0.9701 and 0.9139
Full‐matrix least‐squares on F2
3391/2/244
R1 = 0.0678, wR2 = 0.1790
0.655 and −0.670 e Å–3
Figure 1. The molecular structure of 6a.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2012 Synthesis, Crystal Structure, and Fungicidal Activity of Novel 1,5‐Diaryl‐1H‐pyrazol‐3‐oxy
Derivatives Containing Oxyacetic Acid or Oxy(2‐thioxothiazolidin‐3‐yl)ethanone Moieties
1373
Figure 2. A partial packing diagram of 6a.
Gibberella zeae and Rhizoctonia cerealis were obtained from
EXPERIMENTAL
Jiangsu Pesticide Research Institute, China.
All reagents were of analytical reagent grade or were chemi-
cally pure. All solvents were dried by standard methods and dis-
tilled before use. Chromatographic purification of products was
carried on flash silica gel (300–400 mesh). TLC was carried out
using Merck Kieselgel 60 GF254 (230–400 mesh) fluorescent
treated silica which were visualized under UV light (254 nm).
Melting points were measured on an X‐4 microscope electro-
thermal apparatus (Taike, China) and were uncorrected. 1H‐
NMR and 13C‐NMR spectra were recorded on a Bruker AV‐500
spectrometer at 500 MHz or a Bruker AV‐300 spectrometer at
300 MHz using CDCl3 or DMSO‐d6 as the solvent, with tetra-
methylsilane as an internal standard. IR spectra were recorded in
KBr disk using a Nicolet 380 FTIR spectrophotometer and only
diagnostic absorbances (λmax) are reported. Elemental analyses
were performed with a Flash EA‐1112 elemental analyzer.
X‐Ray intensity data were recorded on a Bruker SMART 1000
charge coupled device (CCD) diffraction meter using graphite
monochromated Mo Kα radiation (λ = 0.71073) Å.
Table 2
Antifungal activity of newly synthesized compounds (% inhibition).
10 μg mL−1
Synthesis of compounds 4a–4e. The compounds 4a–4d and
new compound 4e were synthesized from methyl 3‐arylacrylates
according to the reported procedure [9]. Spectral data of 4a–4d
match those previously reported [9, 25].
X
Compounds
G. zeae
R. cerealis
H
4a
5a
6a
4b
5b
6b
4c
5c
6c
4d
5d
6d
4e
5e
6e
21.29
−6.84
20.06
1.14
18.44
5.33
9.06
4.92
6.97
2.91
17.15
9.39
0.97
15.53
0.32
2.13
8.54
8.41
0.72
Ethyl 2‐ (5‐ (3‐ chlorophenyl)‐1‐phenyl‐1H‐ pyrazol‐3‐ yloxy)
1
acetate (4e). White crystal; mp 95–96°C; yield: 3.07 g (86%); H‐
4‐OCH3
3‐F
NMR (500 MHz, CDCl3) δ 7.28–7.03 (m, 9H, Ar‐H), 6.05 (s, 1H,
CH), 4.87 (s, 2H, CH2), 4.28 (q, J = 7.5 Hz, 2H, CH2), 1.30 (t, J =
7.5 Hz, 3H, CH3); 13C‐NMR (300 MHz, CDCl3) δ 168.9, 162.3,
142.9, 139.6, 134.4, 132.2, 129.6, 128.9, 128.6, 128.5, 127.1, 126.9,
124.9, 94.3, 65.4, 61.2, 14.2; IR (KBr, ν, cm–1): 3130, 3064, 2983,
2941, 1752, 1638, 1593, 1551, 1500, 1468, 1412, 1377, 1269, 1212,
1153, 1085, 794, 771, 700; Anal. Calcd. for C19H17ClN2O3: C
63.96, H 4.80, N 7.85; found C 63.87, H 4.81, N 7.82.
−4.18
11.42
30.25
16.36
30.56
39.20
23.15
52.74
23.38
13.27
28.66
4‐Cl
3‐Cl
Synthesis of compounds 5a–5e. General Procedure.To a
solution of 4a–4e (10 mmol) in 95% ethanol (40 mL), sodium
hydroxide (0.42 g, 10.5 mmol) was added. The mixture was then
Journal of Heterocyclic Chemistry
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Y. Liu, G. He, C. Kai, Y. Li, and H. Zhu
Vol 49
stirred at room temperature until the starting material had been
completely consumed as judged by TLC analysis. The solvent
was evaporated under reduced pressure and water (10 mL)
was added with good stirring. The aqueous layer was extracted
with ethyl acetate and then acidified with hydrochloric acid,
allowed to stand, and filtered. The precipitate that formed was
filtered off and dried to furnish the desired compounds 5a–5e
that required no further purification.
gel (50 g) eluting with petroleum ether/ethyl acetate 3:1 to gain the
target compounds 6a–6e.
2‐(1,5‐Diphenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐thioxothiazolidin‐
3‐yl)ethanone (6a). Yellow crystal; mp 187–188°C; yield: 0.28 g
1
(71%); H‐NMR (500 MHz, CDCl3) δ 7.30–7.20 (m, 10H, Ar‐H),
6.04 (s, 1H, CH), 5.71 (s, 2H, CH2), 4.60 (t, J = 7.5 Hz, 2H, CH2),
3.37 (t, J = 7.5 Hz, 2H, CH2); 13C‐NMR (300 MHz, CDCl3) δ
201.1, 170.4, 162.2, 144.5, 140.0, 130.6, 128.7, 128.6, 128.4, 126.7,
124.8, 94.0, 69.7, 55.5, 29.7; IR (KBr, ν, cm–1): 3154, 3054, 2948,
1699, 1594, 1550, 1503, 1471, 1361, 1276, 1223, 1178, 1145, 1073,
964, 914, 875, 756, 696; Anal. Calcd. for C20H17N3O2S2: C 60.74,
2‐(1,5‐Diphenyl‐1H‐pyrazol‐3‐yloxy)acetic acid (5a). White
1
crystal; mp 105–106°C; yield: 1.88 g (64%); H‐NMR (300 MHz,
DMSO‐d6) δ 12.91 (s, 1H, OH), 7.39–7.17 (m, 10H, Ar‐H), 6.20 (s,
1H, CH), 4.76 (s, 2H, CH2); 13C‐NMR (300 MHz, CDCl3) δ 173.4,
162.1, 144.9, 139.7, 130.3, 128.8, 128.7, 128.6, 128.5, 127.0, 125.0,
93.8, 65.2; IR (KBr, ν, cm–1): 3419, 2913, 2774, 2664, 2575, 1744,
1595, 1548, 1503, 1421, 1310, 1257, 1207, 1152, 1081, 918, 759,
696; Anal. Calcd. for C17H14N2O3: C 69.38, H 4.79, N 9.52; found
C 69.46, H 4.80, N 9.49.
2‐(5‐(4‐Methoxyphenyl)‐1‐phenyl‐1H‐pyrazol‐3‐yloxy)acetic acid
(5b). White crystal; mp 167–168°C; yield: 2.14 g (66%); 1H‐NMR
(500 MHz, DMSO‐d6) δ 12.82 (s, 1H, OH), 7.38–6.90 (m, 9H, Ar‐
H), 6.11 (s, 1H, CH), 4.74 (s, 2H, CH2), 3.75 (s, 3H, OCH3); 13C‐
NMR (300 MHz, DMSO‐d6) δ 169.9, 162.0, 159.3, 143.9, 139.7,
129.7, 128.9, 126.9, 124.7, 122.2, 114.0, 93.0, 64.7, 55.1; IR (KBr,
n, cm–1): 3432, 2923, 1745, 1601, 1553, 1510, 1475, 1422, 1258,
1203, 1153, 1078, 819, 765, 697; Anal. Calcd. for C18H16N2O4: C
66.66, H 4.97, N 8.64; found C 66.72, H 4.96, N 8.67.
2‐(5‐(3‐Fluorophenyl)‐1‐phenyl‐1H‐ pyrazol‐3‐yloxy)acetic
acid (5c). White crystal; mp 141–142°C; yield: 1.91 g (61%);
1H‐NMR (500 MHz, DMSO‐d6) δ 12.86 (s, 1H, OH), 7.39–
7.17 (m, 9H, Ar‐H), 6.20 (s, 1H, CH), 4.75 (s, 2H, CH2); 13C‐
NMR (300 MHz, DMSO‐d6) δ 169.9, 163.6, 162.0, 143.0,
139.4, 130.7, 130.6, 129.0, 127.1, 126.4, 124.8, 115.7, 115.4,
93.7, 64.8; IR (KBr, ν, cm–1): 3415, 3064, 2912, 2772, 2665,
2574, 1747, 1591, 1551, 1504, 1423, 1257, 1150, 1083, 865,
767, 696; Anal. Calcd. for C17H13FN2O3: C 65.38, H 4.20, N
8.97; found C 65.45, H 4.21, N 8.94.
2‐(5‐(4‐ Chlorophenyl)‐1‐ phenyl‐1H‐ pyrazol‐3‐yloxy)acetic
acid (5d). White crystal; mp 159–160°C; yield: 2.01 g (61%); 1H‐
NMR (300 MHz, DMSO‐d6) δ 12.92 (s, 1H, OH), 7.44–7.18 (m,
9H, Ar‐H), 6.24 (s, 1H, CH), 4.75 (s, 2H, CH2); 13C‐NMR (300
MHz, DMSO‐d6) δ 169.7, 162.0, 143.9, 139.3, 133.3, 130.1,
129.0, 128.6, 128.0, 127.2, 124.8, 93.7, 65.0; IR (KBr, ν, cm–1):
3412, 3063, 2781, 1747, 1600, 1549, 1504, 1427, 1239, 1089,
1062, 1017, 838, 768, 696; Anal. Calcd. for C17H13ClN2O3: C
62.11, H 3.99, N 8.52; found C 62.19, H 3.98, N 8.55.
H 4.33, N 10.62; found C 60.66, H 4.34, N 10.66.
2‐(5‐(4‐Methoxyphenyl)‐1‐phenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐
thioxothiazolidin‐3‐yl)ethanone (6b). Yellow crystal; mp 162–
163°C; yield: 0.29 g (68%); 1H‐NMR (500 MHz, CDCl3) δ 7.
27–6.80 (m, 9H, Ar‐H), 5.98 (s, 1H, CH), 5.70 (s, 2H, CH2), 4.60
(t, J = 7.6 Hz, 2H, CH2), 3.80 (s, 3H, OCH3), 3.37 (t, J = 7.6 Hz,
2H, CH2); 13C‐NMR (300 MHz, CDCl3) δ 201.1, 170.4, 162.1,
159.7, 144.4, 140.1, 130.0, 128.6, 126.5, 124.8, 123.0, 113.8, 93.5,
69.7, 55.5, 55.2, 29.7; IR (KBr, ν, cm–1): 3033, 2928, 2854, 1712,
1602, 1553, 1510, 1476, 1448, 1378, 1263, 1228, 1161, 1073, 967,
765, 697; Anal. Calcd. for C21H19N3O3S2: C 59.27, H 4.50, N
9.87; found C 59.36, H 4.49, N 9.90.
2‐(5‐(3‐Fluorophenyl)‐1‐phenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐
thioxothiazolidin‐3‐yl)ethanone (6c). Yellow crystal; mp 121–
122°C; yield: 0.29 g (70%); 1H‐NMR (500 MHz, CDCl3) δ
7.31–6.91 (m, 9H, Ar‐H), 6.06 (s, 1H, CH), 5.72 (s, 2H, CH2),
4.60 (t, J = 7.6 Hz, 2H, CH2), 3.37 (t, J = 7.6 Hz, 2H, CH2);
13C‐NMR (300 MHz, CDCl3) δ 201.1, 170.3, 164.1, 162.2,
143.2, 139.7, 132.5, 130.1, 128.8, 127.1, 124.9, 124.5, 115.9,
115.6, 94.4, 69.8, 55.5, 29.7; IR (KBr, ν, cm–1): 3063, 2928,
2854, 1710, 1590, 1553, 1502, 1447, 1368, 1279, 1228, 1172,
1059, 864, 779, 696, 671; Anal. Calcd. for C20H16FN3O2S2: C
58.09, H 3.90, N 10.16; found C 58.18, H 3.91, N 10.12.
2‐(5‐(4‐Chlorophenyl)‐1‐phenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐
thioxothiazolidin‐3‐yl)ethanone (6d). Yellow crystal; mp 132–
133°C; yield: 0.30 g (71%); 1H‐NMR (500 MHz, CDCl3) δ 7.
49–7.18 (m, 9H, Ar‐H), 6.03 (s, 1H, CH), 5.71 (s, 2H, CH2), 4.60
(t, J = 7.6 Hz, 2H, CH2), 3.37 (t, J = 7.6 Hz, 2H, CH2); 13C‐NMR
(300 MHz, CDCl3) δ 201.1, 170.3, 162.3, 143.0, 139.7, 134.2,
131.0, 129.9, 128.9, 127.2, 126.7, 124.9, 94.4, 69.8, 55.5, 29.7; IR
(KBr, ν, cm–1): 2926, 2855, 1705, 1671, 1611, 1548, 1505, 1459,
1402, 1369, 1325, 1265, 1222, 1159, 1087, 1054, 916, 814, 749,
696; Anal. Calcd. for C20H16ClN3O2S2: C 55.87, H 3.75, N 9.77;
found C 55.75, H 3.76, N 9.74.
2‐(5‐(3‐Chlorophenyl)‐1‐ phenyl‐1H‐pyrazol‐3‐yloxy)‐1‐(2‐
thioxothiazolidin‐3‐yl)ethanone (6e). Yellow crystal; mp 143–
144°C; yield: 0.31 g (73%); 1H‐NMR (500 MHz, CDCl3) δ 7.
30–7.05 (m, 9H, Ar‐H), 6.05 (s, 1H, CH), 5.72 (s, 2H, CH2), 4.60
(t, J = 7.6 Hz, 2H, CH2), 3.37 (t, J = 7.6 Hz, 2H, CH2); 13C‐NMR
(500 MHz, CDCl3) δ 201.1, 170.3, 162.3, 143.0, 139.7, 134.4,
132.3, 129.7, 128.9, 128.7, 128.6, 127.1, 127.0, 124.9, 94.4, 69.8,
55.5, 29.7; IR (KBr, ν, cm–1): 3128, 3060, 2927, 2851, 1706, 1594,
1549, 1501, 1468, 1441, 1368, 1279, 1224, 1187, 1054, 879, 767,
695, 672; Anal. Calcd. for C20H16ClN3O2S2: C 55.87, H 3.75, N
9.77; found C 55.78, H 3.74, N 9.80.
2‐(5‐(3‐Chlorophenyl)‐1‐phenyl‐1H‐ pyrazol‐3‐yloxy)acetic
acid (5e). White crystal; mp 172–173°C; yield: 2.07 g (63%); 1H‐
NMR (500 MHz, CDCl3) δ 9.48 (s, 1H, OH), 7.32–7.03 (m, 9H, Ar‐
H), 6.04 (s, 1H, CH), 4.92 (s, 2H, CH2); 13C‐NMR (300 MHz,
CDCl3) δ 173.5, 162.1, 143.2, 139.4, 134.4, 132.0, 130.0, 129.7,
129.0, 128.7, 127.3, 126.9, 125.0, 94.2, 65.0; IR (KBr, n, cm–1):
3411, 3064, 2911, 2771, 2666, 2573, 1747, 1591, 1551, 1501, 1421,
1256, 1085, 919, 865, 767, 696; Anal. Calcd. for C17H13ClN2O3: C
62.11, H 3.99, N 8.52; found C 62.21, H 3.40, N 8.55.
Synthesis of compounds 6a–6e. General Procedure. Compounds
5a–5e (1.0 mmol) was dissolved in a solution of DCC (0.22 g, 1.05
mmol) in CH2Cl2 (50 mL), and the mixture was stirred at 0°C for 1
h. Then thiazolidine‐2‐thione (0.12 g, 1.0 mmol) and DMAP (0.01 g,
0.1 mmol) was added. The solution was stirred at 0°C for 2 h and
then at room temperature for 12 h. The white precipitate was filtered
off, and the solvent was evaporated under reduced pressure. The
residue was then purified by flash column chromatography over silica
Acknowledgments. The authors gratefully acknowledge the
financial support of the National High Technology Research
and Development Program (“863” Program) of China
(2009AA032901). The authors also thank Jiangsu Pesticide
Research Institute Co., Ltd., for the test of fungicidal activity.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2012 Synthesis, Crystal Structure, and Fungicidal Activity of Novel 1,5‐Diaryl‐1H‐pyrazol‐3‐oxy
Derivatives Containing Oxyacetic Acid or Oxy(2‐thioxothiazolidin‐3‐yl)ethanone Moieties
1375
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They also thank the Center of Test and Analysis, Nanjing
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet