Synthesis and herbicidal activity of acylpyrazole derivatives containing 1,2,3-thiadiazole moiety

Article abstract of DOI:10.1002/jhet.790

A series of novel acylpyrazole derivatives containing 1,2,3-thiadiazole ring 3a-3m were synthesized by the condensations of 1-phenyl-3-methyl-4- (substituted benzal or 4-methyl-1,2,3-thiadiazole-5-carbonyl)-5-hydroxypyrazole 2 with 4-methyl-1,2,3-thiadiaz

Full text of DOI:10.1002/jhet.790

732
Synthesis and Herbicidal Activity of Acylpyrazole Derivatives
Containing 1,2,3-Thiadiazole Moiety
Vol 49
*
Feng Cheng and De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of
Chemistry, Central China Normal University, Wuhan 430079, Hubei, People’s Republic of China
*
E-mail: chshidq@mail.ccnu.edu.cn
Received October 5, 2010
DOI 10.1002/jhet.790
View this article online at wileyonlinelibrary.com.
A series of novel acylpyrazole derivatives containing 1,2,3-thiadiazole ring 3a–3m were synthesized
by the condensations of 1-phenyl-3-methyl-4-(substituted benzal or 4-methyl-1,2,3-thiadiazole-5-carbonyl)-
5-hydroxypyrazole 2 with 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride or substituted benzoyl chloride.
1
Their structures were confirmed by IR, H-NMR, mass spectroscopy, and elemental analyses. The results
of preliminary bioassays showed that some of the title compounds 3 exhibited moderate to good herbicidal
activities against dicotyledonous plants (Brassica campestris L.) at the concentration of 100 mg/L. For
example, compounds 3e, 3f, 3g, and 3k possessed 74.6%, 72.2%, 70.3%, and 84.5% inhibition against B.
campestris L., respectively, whereas commercially available herbicide Sulcotrione showed only 35.0%
inhibition at the same concentration. Moreover, these compounds displayed higher herbicidal activity against
B. campestris L. than Echinochloa crus-galli. However, these compounds showed weak activities at the
concentration of 10 mg/L.
J. Heterocyclic Chem., 49, 732 (2012).
INTRODUCTION
activators, which induces fungicide resistance in rice
plants; however, thidiazuron was used as plant growth
regulator (Fig. 1). To find novel HPPD inhibitor lead
compounds with high activity and low toxicity, based
on the commercial HPPD herbicides, pyrazolate and
pyrazoxyfen as lead compounds, we designed and syn-
thesized a series of novel acylpyrazole derivatives con-
taining 1,2,3-thiadiazole ring 3. Herein, we would like
to report the synthesis and herbicidal activities of the ti-
tle compounds 3 in this article (Scheme 1).
(4-Hydroxyphenyl)pyruvate dioxygenase (HPPD, EC
1.13.11.27) is a nonheme Fe(II)-dependent enzyme that
catalyzes the conversion of (4-hydroxyphenyl)pyruvate
(HPP) to homogentisate in the tyrosine catabolism path-
way. Continued scientific interest in HPPD has arisen due
to the importance of this enzyme in the treatment of type
1 tyrosinemia and alkaptonuria and its use as a target for
the development of herbicides [1–4]. The benzoylpyrazole
derivatives represent a relatively new class of highly ac-
tive, bleaching herbicides, which are a subset of a larger
class of “diketone” herbicides [5,6]. For example, pyrazo-
late [7] and pyrazoxyfen (Fig. 1) [8], as two commercial
rice herbicides, acted as prodrugs for HPPD inhibitors.
So, the benzoylpyrazole area chemistry attracted more
and more attention. Recently, 1,2,3-thiadiazole derivatives
as one kind of nitrogen heterocyclic compounds with a
wide spectrum of remarkable biological activities are widely
used as agrochemicals [9–11]. For example, acibenzolar-S-
methyl and tiadinil were developed and used as plant
RESULTS AND DISCUSSION
1-Phenyl-3-methyl-4-(substituted benzal or 4-methyl-
1,2,3-thiadiazole-5-carbonyl)-5-hydroxypyrazole 2 were
synthesized via the Scotton–Baumann reaction of pyrazo-
lone 1 and substituted benzoyl chlorides or 4-methyl-
1,2,3-thiadiazole-5-carbonyl chloride, followed by the
Fries rearrangement in the presence of calcium hydroxide
as the catalyst [12,13]. On one hand, calcium hydroxide
© 2012 HeteroCorporation

July 2012
Synthesis and Herbicidal Activity of Acylpyrazole Derivatives Containing
1,2,3-Thiadiazole Moiety
733
Table 1
The herbicidal activities of compounds 3a–3m (in vitro, percent
inhibition).
B. campestris
root test
E. crus-galli
cup test
Compound
100 mg/L
10 mg/L
100 mg/L
10 mg/L
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
64.5
68.3
68.5
12.4
74.6
72.2
70.3
64.9
54.6
63.5
84.5
41.3
31.0
35.0
0
0
0
0
0
0
0
0
0
3.0
37.2
0
0
0
10.0
20.0
5.0
10.0
10.0
20.0
30.0
30.0
30.0
0
5.0
0
0
0
0
15.0
15.0
10.0
15.0
0
0
15.0
0
Figure 1. Some commercial pyrazole and 1,2,3-thiadiazole pesticides.
can remove hydrochloride formed in the Scotton–Baumann
reaction; so it can improve the yields of the Scotton–Baumann
reaction. On the other hand, calcium ion can form the
complex with the benzoyl hydroxypyrazole 2 and pre-
vent the multiacylation reaction of pyrazolone. Finally,
2 reacted with substituted benzoyl chloride or 4-
methyl-1,2,3-thiadiazole-5-carbonyl chloride in the pres-
ence of triethylamine in chloroform with an ice-bath
cooling to get the title compounds 3 in moderate to ex-
cellent yields.
5.0
20.0
25.0
35.0
3m
Sulcotrione
30.0
grass) has been investigated at the dosages of 100 and
10 mg/L and compared with the commercially available
herbicide, Sulcotrione, according to the method described
in Experimental section and are listed in Table 1. The
results of preliminary bioassays showed that some of the
title compounds 3 exhibited moderate to good herbicidal
activities against dicotyledonous plants (B. campestris L.)
at the concentration of 100 mg/L. For example, compounds
3e, 3f, 3g, and 3k possessed 74.6%, 72.2%, 70.3%, and
84.5% inhibition against B. campestris L., respectively,
whereas commercially available herbicide Sulcotrione
showed only 35.0% inhibition at the same concentration.
For the preliminary structure–activity relationships, as the
data shown in Table 1, we noticed that the different
substituents in benzene ring have some influence on the
herbicidal activity. For compounds 3a–3g, the compounds
with an electron-releasing group in the benzene ring
displayed better herbicidal activity against B. campestris L.
than those with electron-donating one; so compound 3d
(R = p-CH3) showed the weakest herbicidal activity.
This result can be explained by the fact that those
compounds with an electron-releasing group in the
benzene ring are more easily hydrolyzed to 5-hydroxy
acylpyrazole than those with an electron-donating one;
hence 5-hydroxy acylpyrazole can combine with Fe(II)
ion and exhibit better HPPD inhibitory activity. As for
compounds 3h–3m, compound 3k (R = p-CH3) displayed
the best herbicidal activity against B. campestris L.,
whereas compounds 3l (R = 4-F) and 3m (R = 2-NO2)
showed the weakest herbicidal activity; however, the
reason is not very clear.
The structures of compounds 3 were deduced from their
spectral data (IR, 1H-NMR, and EI-MS or ESI-MS) and el-
emental analyses, which were listed in the Experimental
1
section. In the H-NMR spectra of compounds 3h–3m,
the two methyl protons with attached pyrazole and thiadia-
zole rings were displayed as two singlets with chemical
shift d ca. 2.5 and 2.8, respectively; the aromatic protons
were exhibited as multiple peaks with chemical shifts d
ca. 7.4–8.6. IR spectra of compounds 3 showed normal
stretching absorption bands, indicating the existence Ar—H
(∼3050 cmꢀ1), C¼O (∼1760, ∼1650 cmꢀ1), Ar (1580,
1510, 1480 cmꢀ1), C—O—C (∼1240, ∼1060 cmꢀ1). The
EI or ESI mass spectra of compounds 3 revealed the existence
of the molecular ion peaks or strong M + K ꢀ 1 or M + Na
peaks, which were in good accordance with the given struc-
tures of products.
Herbicidal activity. The preliminary herbicidal activity
(in vitro) of the title compounds 3 against Brassica
campestris L. (rape) and Echinochloa crus-galli (barnyard
Scheme 1. Synthetic route to compounds 3a–3m.
Moreover, these compounds displayed higher herbicidal
activity against dicotyledonous plant (B. campestris L.)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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F. Cheng and D.-Q. Shi
Vol 49
CDCl3): d 2.35 (s, 3H, CH3), 7.31–7.38 (m, 4H, ArH), 7.44 (t,
J = 7.8 Hz, 2H, ArH), 7.52 (d, J = 7.8 Hz, 2H, ArH), 7.65 (d,
J = 7.2 Hz, 2H, ArH), 15.56 (s, 1H, OH). Anal. Calcd for
C17H14N2O2: C, 73.37; H, 5.07; N, 10.07. Found: C, 73.18; H,
4.93; N, 10.20.
1-Phenyl-3-methyl-4-(4-chlorobenzal)-5-hydroxypyrazole (2c).
White solid, yield: 86%, mp 105–107ꢁC; 1H-NMR (600 MHz,
CDCl3): d 2.36 (s, 3H, CH3), 7.35 (d, J = 7.8 Hz, 2H, ArH),
7.42 (t, J = 7.8 Hz, 1H, ArH), 7.48 (t, J = 7.2 Hz, 2H, ArH),
7.53 (d, J = 7.2 Hz, 2H, ArH), 7.62 (d, J = 7.8 Hz, 2H, ArH),
15.73 (s, 1H, OH). Anal. Calcd for C17H13ClN2O2: C, 65.29;
H, 4.19; N, 8.96. Found: C, 65.37; H, 4.30; N, 9.05.
than monocotyledonous one (E. crus-galli). However,
these compounds showed weak herbicidal activities at the
concentration of 10 mg/L. Further evaluation of biological
activity and investigation of their structure–activity rela-
tionship are on the way.
In conclusion, a series of novel acylpyrazole derivatives
containing 1,2,3-thiadiazole ring 3a–3m were designed and
synthesized. The results of preliminary bioassays showed
that some of the title compounds 3 exhibited moderate to
good herbicidal activities at the concentration of 100 mg/L.
Moreover, these compounds displayed higher herbicidal
activity against dicotyledonous plants (B. campestris L.)
than monocotyledonous one (E. crus-galli). However, the
target compounds 3 showed weak activities at the concentra-
tion of 10 mg/L.
1-Phenyl-3-methyl-4-(4-nitrobenzal)-5-hydroxypyrazole
1
(2d). White solid, yield: 75%, mp 190–192ꢁC; H-NMR (600
MHz, CDCl3): d 2.34 (s, 3H, CH3), 7.42 (t, J = 7.2 Hz, 1H,
ArH), 7.47 (t, J = 7.8 Hz, 2H, ArH), 7.53 (d, J = 7.8 Hz,
2H, ArH), 7.90 (d, J = 8.4 Hz, 2H, ArH), 8.26 (d, J = 9.0
Hz, 2H, ArH), 15.89 (s, 1H, OH). Anal. Calcd for
C17H13N3O4: C, 63.16; H, 4.05; N, 13.00. Found: C, 63.04;
H, 4.16; N, 12.86.
EXPERIMENTAL
1-Phenyl-3-methyl-4-(2-methylbenzal)-5-hydroxypyrazole (2e).
Light yellow solid, yield: 84%, mp 105–106ꢁC; 1H-NMR (600
MHz, CDCl3): d 2.29 (s, 3H, CH3), 2.45 (s, 3H, CH3), 7.14 (d,
J = 7.2 Hz, 2H, ArH), 7.40 (t, J = 7.2 Hz, 1H, ArH), 7.45 (t,
J = 7.8 Hz, 2H, ArH), 7.53 (d, J = 7.2 Hz, 2H, ArH), 7.61 (d,
J = 7.8 Hz, 2H, ArH), 15.90 (s, 1H, OH). Anal. Calcd for
C18H16N2O2: C, 73.95; H, 5.52; N, 9.58. Found: C, 73.74; H,
5.57; N, 9.73.
Melting points were determined with a WRS-1B digital
melting point apparatus and were uncorrected. H-NMR spectra
1
were recorded with a Varian Mercury PLUS 600 (600 MHz)
spectrometer with TMS as the internal reference and CDCl3 as
the solvent, while mass spectra were obtained with a Finnigan
TRACEMS2000 spectrometer using the EI method or an Applied
Biosystems API 2000 LC/MS/MS (ESI-MS) spectrometer. IR
spectra were measured by a Nicolet NEXUS470 spectrometer.
Elemental analyses were performed with an Elementar Vario
ELIII CHNSO elemental analyzer. 5-Methyl-2-phenyl-2,4-dihydro-
pyrazol-3-one 1 was obtained by the reaction of ethyl acetylacetate
with phenylhydrazine [14], and 4-methyl-1,2,3-thiadiazole-5-
carbonyl chloride was synthesized according to the reported
methods [15]. All of the solvents and materials were reagent
grade and purified as required.
General procedure for the synthesis of 1-phenyl-3-methyl-4-
(substituted benzal or 4-methyl-1,2,3-thiadiazole-5-carbonyl)-5-
hydroxypyrazole 2. To the stirred solution of 5-methyl-2-phenyl-2,
4-dihydro-pyrazol-3-one 1 (0.52 g, 3 mmol) in anhydrous dioxane
(10 mL), the powders of Ca(OH)2 (0.36 g, 4.8 mmol) and CaO
(0.07 g, 1.2 mmol) were added at 80ꢁC. After the addition was
completed, the solution was stirred under reflux for 20 min.
Substituted benzoyl chloride (3 mmol) or 4-methyl-1,2,3-
thiadiazole-5-carbonyl chloride (0.49 g, 3 mmol) in anhydrous
dioxane (5 mL) was added dropwise with strong stirring. The
mixture was stirred under reflux till the reaction was complete
(monitored by TLC). After the mixture was cooled to room
temperature, dilute hydrochloric acid (2 mol/L, 7.5 mL) was
added; the mixture was allowed to stir for 30 min, and water
(20 mL) was added. The solid was collected by filtration and
recrystallized from the mixture of methanol and water (v/v, 1:1) to
get 2 in 75–86% yields.
1-Phenyl-3-methyl-4-(4-fluorobenzal)-5-hydroxypyrazole (2f).
Colorless solid, yield: 81%, mp 132–133ꢁC; 1H-NMR (600 MHz,
CDCl3): d 2.38 (s, 3H, CH3), 7.07 (t, J = 7.8 Hz, 2H, ArH), 7.43
(d, J = 7.2 Hz, 1H, ArH), 7.51 (t, J = 7.2 Hz, 2H, ArH), 7.56 (d,
J = 7.8 Hz, 2H, ArH), 7.81 (dd, J = 5.4 Hz, J = 7.8 Hz, 2H,
ArH), 15.97 (s, 1H, OH). Anal. Calcd for C17H13FN2O2: C,
68.91; H, 4.42; N, 9.45. Found: C, 68.70; H, 4.56; N, 9.28.
1-Phenyl-3-methyl-4-(2-nitrobenzal)-5-hydroxypyrazole (2g).
1
Light brown solid, yield: 80%, mp 160–162ꢁC; H-NMR (600
MHz, CDCl3): d 2.34 (s, 3H, CH3), 7.45 (d, J = 7.8 Hz, 1H,
ArH), 7.51 (t, J = 7.2 Hz, 2H, ArH), 7.56 (t, J = 7.2 Hz, 2H,
ArH), 7.62 (t, J = 7.8 Hz, 1H, ArH), 8.09 (d, J = 7.8 Hz, 1H,
ArH), 8.31 (d, J = 7.8 Hz, 1H, ArH), 8.54 (s, 1H, ArH), 15.99
(s, 1H, OH). Anal. Calcd for C17H13N3O4: C, 63.16; H, 4.05;
N, 13.00. Found: C, 63.41; H, 3.88; N, 12.92.
General procedure for the synthesis of pyrazole derivatives
containing 1,2,3-thiadiazole ring 3. Compound 2 (2.0 mmol),
triethylamine (0.22 g, 2.2 mmol), and anhydrous chloroform
(10 mL) were added to a three-necked flask; a solution of 4-methyl-
1,2,3-thiadiazole-5-carbonyl chloride (0.32 g, 2.0 mmol) or
substituted benzoyl chloride (2.0 mmol) in anhydrous
chloroform (5 mL) was added dropwise slowly with an ice-bath
cooling. After the addition was completed, the mixture was
stirred at room temperature for 4–8 h till the reaction was
complete (monitored by TLC). The work-up involved washing
with 5% hydrochloric acid, 5% NaHCO3, and brine,
respectively. After phase separation, drying over anhydrous
sodium sulfate, filtration and evaporation, the crude product
was recrystallized from the mixture of petroleum ether and
ethyl acetate to give the target compounds 3 in 63–85% yields.
Data for 3a (Ar = C6H5). White solid, yield: 84%, mp 93–
94ꢁC; IR: Ar—H 3086, C¼O 1751, 1687, Ar 1515, 1478, 1450,
C—O—C 1262, 1204 cmꢀ1; 1H-NMR (600 MHz, CDCl3): d 2.52
(s, 3H, CH3), 2.74 (s, 3H, CH3), 7.37 (t, J = 7.2 Hz, 1H, Ar—H),
1-Phenyl-3-methyl-4-(4-methyl-1,2,3-thiadiazole-5-carbonyl)-
5-hydroxypyrazole (2a). Light brown solid, yield: 76%, mp 93–95ꢁC;
1H-NMR (CDCl3, 600 MHz): d 1.96 (s, 3H, CH3), 2.81 (s, 3H,
CH3), 7.36 (t, J = 6.6 Hz, 1H, Ar—H), 7.50 (t, J = 8.4 Hz, 2H,
Ar—H), 7.82 (s, 2H, Ar—H), 15.84 (s, 1H, OH). Anal. Calcd for
C14H12N4O2S: C, 55.99; H, 4.03; N, 18.65. Found: C, 55.83; H,
4.15; N, 18.71.
1-Phenyl-3-methyl-4-(benzal)-5-hydroxypyrazole (2b). Light
yellow solid, yield: 83%, mp 89–90ꢁC; 1H-NMR (600 MHz,
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DOI 10.1002/jhet

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Synthesis and Herbicidal Activity of Acylpyrazole Derivatives Containing
1,2,3-Thiadiazole Moiety
735
7.42–7.45 (m, 4H, Ar—H), 7.55 (q, J = 7.8 Hz, 2H, Ar—H), 7.61–
7.64 (m, 1H, Ar—H), 7.77 (q, J = 8.4 Hz, 2H, Ar—H); ESI-MS: m/z
426 (M + Na ꢀ 1, 100), 404 (M, 65). Anal. Calcd for C21H16N4O3S:
C, 62.36; H, 3.99; N, 13.85. Found: C, 62.15; H, 3.71; N, 13.64.
Data for 3b (Ar = 4-FC6H4). Orange crystals, yield: 63%, mp
107–108ꢁC; IR: Ph—H 2984, C¼O 1764, 1651, Ph 1557, 1502,
1475, C—O—C 1236, 1195 cmꢀ1; 1H-NMR (600 MHz, CDCl3):
d 2.50 (s, 3H, CH3), 2.74 (s, 3H, CH3), 7.11 (t, J = 8.4 Hz, 2H,
ArH), 7.37–7.44 (m, 3H, ArH), 7.53 (d, J = 8.4 Hz, 2H, ArH),
7.80 (dd, J = 4.8 Hz, J = 8.4 Hz, 2H, ArH); ESI-MS: m/z 460
(M + K ꢀ 1, 45), 444 (M + Na ꢀ 1, 83), 422 (M, 100). Anal.
Calcd for C21H15FN4O3S: C, 59.71; H, 3.58; N, 13.26. Found:
C, 59.87; H, 3.32; N, 13.05.
ArH), 8.29 (d, J = 8.4 Hz, 2H, ArH); ESI-MS: m/z 472 (M + Na,
36), 449 (M+, 100). Anal. Calcd for C21H15N5O5S: C, 56.12; H,
3.36; N, 15.58. Found: C, 56.34; H, 3.40; N, 15.31.
Data for 3h (Ar = C6H5). White solid, yield: 85%, mp 137–
138ꢁC; IR: Ph—H 2929, C¼O 1766, 1648, Ph 1552, 1505,
1
1471, 1448, C—O—C 1198, 1064 cmꢀ1; H-NMR (600 MHz,
CDCl3): d 2.43 (s, 3H, CH3), 2.78 (s, 3H, CH3), 7.35–7.41 (m,
4H, ArH), 7.46 (t, J = 7.8 Hz, 2H, ArH), 7.54 (d, J = 7.8 Hz,
2H, ArH), 7.68 (d, J = 7.2 Hz, 2H, ArH); EI-MS (70 eV): m/z
404 (M+, 3.6), 278 (95), 200 (58), 132 (23), 105 (100), 91 (44),
77 (97). Anal. Calcd for C21H16N4O3S: C, 62.36; H, 3.99; N,
13.85. Found: C, 62.41; H, 3.75; N, 13.92.
Data for 3i (Ar = 4-ClC6H4). White solid, yield: 76%, mp 95–
96 ꢁC; IR: Ph—H 2930, C¼O 1770, 1641, Ph 1559, 1509, 1470,
1442, C—O—C 1195, 1061 cmꢀ1; 1H-NMR (600 MHz, CDCl3):
d 2.38 (s, 3H, CH3), 2.83 (s, 3H, CH3), 7.37 (d, J = 8.4 Hz, 2H,
ArH), 7.46 (t, J = 7.8 Hz, 1H, ArH), 7.47 (t, J = 7.2 Hz, 2H,
ArH), 7.54 (d, J = 7.2 Hz, 2H, ArH), 7.66 (d, J = 8.4 Hz, 2H,
ArH); EI-MS (70 eV): m/z 438 (M+, 2.1), 312 (43), 278 (25), 200
(100), 139 (65), 111 (34), 91 (48), 77 (33). Anal. Calcd for
C21H15ClN4O3S: C, 57.47; H, 3.44; N, 12.77. Found: C, 57.29; H,
3.48; N, 12.60.
Data for 3c (Ar = 2-FC6H4). Colorless solid, yield: 82%, mp
103–104ꢁC; IR: Ph—H 3077, 2927, C¼O 1772, 1650, Ph 1612,
1
1550, 1465, 1450, C—O—C 1229, 1062 cmꢀ1; H-NMR (600
MHz, CDCl3): d 2.50 (s, 3H, CH3), 2.76 (s, 3H, CH3), 7.15
(t J = 9.6 Hz, 1H, ArH), 7.20 (t, J = 8.4 Hz, 1H, ArH), 7.39
(d, J = 7.2 Hz, 1H, ArH), 7.45 (t, J = 7.2 Hz, 2H, ArH), 7.58–7.62
(m, 3H, ArH), 7.67 (t, J = 7.2 Hz, 1H, ArH); EI-MS: m/z 422
(M+, 4.6), 272 (100), 244 (35), 201 (42), 160 (48), 128 (41),
91 (39.5), 77 (85), 71 (38). Anal. Calcd for C21H15FN4O3S:
C, 59.71; H, 3.58; N, 13.26. Found: C, 59.53; H, 3.66; N,
13.31.
Data for 3j (Ar = 4-NO2C6H4). Light brown solid, yield: 78%,
mp 140–142ꢁC; IR: Ph—H 2934, C¼O 1768, 1645, Ph 1552,
1
Data for 3d (Ar = 4-CH3C6H4). Colorless solid, yield: 79%,
1502, 1474, 1445, C—O—C 1196, 1066 cmꢀ1; H-NMR (600
mp 117–118ꢁC; IR: Ph—H 2931, C¼O 1755, 1642, Ph 1529,
MHz, CDCl3): d 2.32 (s, 3H, CH3), 2.86 (s, 3H, CH3), 7.45 (t,
J = 7.2 Hz, 1H, ArH), 7.49 (t, J = 7.8 Hz, 2H, ArH), 7.55
(d, J = 7.8 Hz, 2H, ArH), 7.87 (d, J = 8.4 Hz, 2H, ArH),
8.28 (d, J = 9.0 Hz, 2H, ArH); ESI-MS: m/z 477 (M + K ꢀ 1, 78),
1
1467, 1446, C—O—C 1241, 1063 cmꢀ1; H-NMR (600 MHz,
CDCl3): d 2.41 (s, 3H, CH3), 2.53 (s, 3H, CH3), 2.74 (s, 3H,
CH3), 7.21 (d, J = 7.2 Hz, 2H, ArH), 7.35 (t, J = 7.2 Hz, 1H,
ArH), 7.42 (t, J = 7.2 Hz, 2H, ArH), 7.54 (d, J = 7.8 Hz, 2H,
ArH), 7.64 (d, J = 7.8 Hz, 2H, ArH); 13C-NMR (150 MHz,
CDCl3): d 12.99, 14.85, 21.87, 111.43, 122.79, 123.31, 128.66,
129.40, 129.69, 130.13, 136.46, 145.78, 146.61, 147.15, 151.16,
158.31, 162.00, 179.40; ESI-MS (70 eV): m/z 418 (M+, 6.7), 272
(100), 244 (34), 201 (40), 160 (43), 141 (12), 113 (15), 91 (18), 77
(45), 51 (10). Anal. Calcd for C22H18N4O3S: C, 63.14; H, 4.34;
N, 13.39. Found: C, 63.04; H, 4.40; N, 13.13.
472 (M
+ Na, 100), 449 (M+, 52). Anal. Calcd for
C21H15N5O5S: C, 56.12; H, 3.36; N, 15.58. Found: C, 56.06;
H, 3.44; N, 15.67.
Data for 3k (Ar = 4-CH3C6H4). Colorless solid, yield: 73%,
mp 148–149ꢁC; IR: Ph—H 2936, C¼O 1762, 1648, Ph 1545,
1
1506, 1480, 1441, C—O—C 1204, 1065 cmꢀ1; H-NMR (600
MHz, CDCl3): d 2.27 (s, 3H, CH3), 2.43 (s, 3H, CH3), 2.80 (s,
3H, CH3), 7.15 (d, J = 7.8 Hz, 2H, ArH), 7.41 (t, J = 7.2 Hz,
1H, ArH), 7.47 (t, J = 7.8 Hz, 2H, ArH), 7.55 (d, J = 7.2 Hz,
2H, ArH), 7.60 (d, J = 7.8 Hz, 2H, ArH); ESI-MS: m/z 456
(M+K-1, 45), 440 (M + Na ꢀ 1, 78), 418 (M+, 100). Anal.
Calcd for C22H18N4O3S: C, 63.14; H, 4.34; N, 13.39. Found: C,
63.37; H, 4.61; N, 13.10.
Data for 3e (Ar = 2-ClC6H4). White solid, yield: 73%, mp
86–87ꢁC; IR: Ph—H 2947, C¼O 1762, 1651, Ph 1536, 1462,
1440, C—O—C 1243, 1065 cmꢀ1
;
1H-NMR (600 MHz,
CDCl3): d 2.47 (s, 3H, CH3), 2.78 (s, 3H, CH3), 7.31 (t, J = 7.8 Hz,
1H, ArH), 7.41 (d, J = 7.2 Hz, 1H, ArH), 7.45–7.48 (m, 3H, ArH),
7.49 (t, J = 7.2 Hz, 1H, ArH), 7.56 (d, J = 7.8 Hz, 2H, ArH), 7.61
(d, J = 7.8 Hz, 1H, ArH); ESI-MS: m/z 460 (M+Na-1, 48),
440 (62), 438 (M, 100). Anal. Calcd for C21H15ClN4O3S: C,
57.47; H, 3.44; N, 12.77. Found: C, 57.61; H, 3.50; N,
12.85.
Data for 3l (Ar = 4-FC6H4). Colorless solid, yield: 76%,
mp 133–135ꢁC; IR: Ph—H 3063, 2930, C¼O 1766, 1648,
Ph 1597, 1553, 1504, 1472, C—O—C 1197, 1063 cmꢀ1
;
1H-NMR (600 MHz, CDCl3): d 2.37 (s, 3H, CH3), 2.83 (s,
3H, CH3), 7.09 (t, J = 8.4 Hz, 2H, ArH), 7.41 (d, J = 7.2
Hz, 1H, ArH), 7.48 (t, J = 7.2 Hz, 2H, ArH), 7.55 (d, J =
7.8 Hz, 2H, ArH), 7.77 (dd, J = 5.4 Hz, J = 7.8 Hz, 2H,
ArH); ESI-MS: m/z 444 (M + Na ꢀ 1, 67), 422 (M+, 100).
Anal. Calcd for C21H15FN4O3S: C, 59.71; H, 3.58; N,
13.26. Found: C, 59.55; H, 3.77; N, 13.03.
Data for 3f (Ar = 4-ClC6H4). White solid, yield: 75%, mp
107–109ꢁC; IR: Ph—H 3102, 2930, C¼O 1760, 1638, Ph
1
1527, 1487, 1446, 1400, C—O—C 1240, 1064 cmꢀ1; H-NMR
(600 MHz, CDCl3): d 2.49 (s, 3H, CH3), 2.74 (s, 3H, CH3),
7.37 (t, J = 7.2 Hz, 1H, ArH), 7.40–7.44 (m, 4H, ArH), 7.52 (d,
J = 7.8 Hz, 2H, ArH), 7.71 (d, J = 7.8 Hz, 2H, ArH); ESI-MS
(70 eV): m/z 438 (M+, 2.7), 271 (6), 207 (5), 139 (100), 111
(18), 77 (7.6). Anal. Calcd for C21H15ClN4O3S: C, 57.47; H,
3.44; N, 12.77. Found: C, 57.56; H, 3.37; N, 12.62.
Data for 3m (Ar = 2-NO2C6H4). White solid, yield: 68%, mp
140–141ꢁC; IR: Ph—H 3012, 2966, C¼O 1745, 1647, Ph 1537,
1
1482, 1445, C—O—C 1252, 1055, cmꢀ1; H-NMR (600 MHz,
CDCl3): d 2.39 (s, 3H, CH3), 2.82 (s, 3H, CH3), 7.43 (d, J = 7.8
Hz, 1H, ArH), 7.49 (t, J = 7.2 Hz, 2H, ArH), 7.56 (t, J = 7.8 Hz,
2H, ArH), 7.63 (t, J = 8.4 Hz, 1H, ArH), 8.07 (d, J = 7.8 Hz, 1H,
ArH), 8.30 (d, J = 9.0 Hz, 1H, ArH), 8.56 (s, 1H, ArH); ESI-MS:
m/z 487 (M + K ꢀ 1, 75), 471 (M + Na ꢀ 1, 100), 449 (M+, 42).
Anal. Calcd for C21H15N5O5S: C, 56.12; H, 3.36; N, 15.58. Found:
C, 56.01; H, 3.14; N, 15.77.
Data for 3g (Ar = 4-NO2C6H4). Light yellow solid, yield:
78%, mp 136–138ꢁC; IR: Ph—H 3005, 2962, C¼O 1741,
1
1643, Ph 1535, 1485, 1446, C—O—C 1257, 1069, cmꢀ1; H-
NMR (600 MHz, CDCl3): d 2.44 (s, 3H, CH3), 2.76 (s, 3H,
CH3), 7.41 (t, J = 7.2 Hz, 1H, ArH), 7.45 (t, J = 7.2 Hz, 2H,
ArH), 7.53 (d, J = 7.2 Hz, 2H, ArH), 8.00 (d, J = 8.4 Hz, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

736
F. Cheng and D.-Q. Shi
Vol 49
Herbicidal Activity (in vitro). The herbicidal evaluation of
Acknowledgment. This work was supported by the Natural Science
Foundation of China (Grant No. 20872046) and the Natural Science
Foundation of Hubei Province (Grant No. 2008CDB086).
compounds 3 was carried out in the laboratory of biological
activities test, State Key Laboratory of Elemento-organic
Chemistry, Nankai University, China. Compounds 3 were
determined with B. campestris L. and E. crus-galli as samples
of annual dicotyledonous and monocotyledonous plants,
respectively, using a previously reported procedure [16]. For
all of the bioassay tests, each treatment was repeated twice.
Treatment. The emulsions of purified compounds were
prepared by dissolving them in N,N-dimethylformamide
(100 μL) with the addition of Tween 20 (2 μL). The mixture
of the same amount of water, N,N-dimethylformamide, and
Tween 20 was used as control. The commercially available
herbicide, Sulcotrione was used as a compared sample to
evaluate the herbicidal activity.
Inhibition of the root growth of rape (B. campestris L.). Rape
seeds were soaked in distilled water for 4 h before being placed on
a filter paper in a 6 cm Petri plate, to which 2 mL of inhibitor
solution had been added in advance. Usually, 10 seeds were used
on each plate. The plate was plaꢁced in a dark room and allowed
to germinate for 72 h at 28 ꢂ 1 C. The lengths of 10 rape roots
selected from each plate were measured, and the means were
calculated. The percentage inhibition was used to describe the
control efficiency of the compounds. The herbicidal activity is
listed in Table 1.
Inhibition of the Seedling Growth of Barnyard Grass
(E. crus-galli). Ten E. crus-galli seeds were placed into a 50
mL cup covered with a layer of glass beads and a piece of
filter paper at the bottom, to which 6 mL of inhibitor solution
had been added in advance. The cup was placed in a bright
room, and the seeds were allowed to germinate for 72 h at
28 ꢂ 1ꢁC. The heights of the above-ground parts of the
seedlings in each cup were measured, and the means were
calculated. The percentage inhibition was used to describe the
control efficiency of the compounds. The herbicidal activity is
also listed in Table 1.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet