The thiazoylmethoxy modification on pyrazole oximes: Synthesis and insecticidal biological evaluation beyond acaricidal activity

Article abstract of DOI:10.1016/j.cclet.2014.06.011

A series of new pyrazole oximes bearing substituted thiazole ring were designed and prepared. The structures of the title compounds were identified by spectral analyses. The results of primary bioassay indicated that some targeted compounds exhibited promising insecticidal activity besides acaricidal activity, particularly; compounds 8c and 8d were more potent against Tetranychus cinnabarinus and Plutella xylostella than other analogues.

Full text of DOI:10.1016/j.cclet.2014.06.011

G Model
CCLET 3044 1–3
Chinese Chemical Letters xxx (2014) xxx–xxx
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Chinese Chemical Letters
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Original article
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The thiazoylmethoxy modification on pyrazole oximes: Synthesis and
insecticidal biological evaluation beyond acaricidal activity
a
a
a
a
Q1 Hong Dai a,b, , Yan-Shuang Xiao , Zhong Li , Xiao-Yong Xu , Xu-Hong Qian
*
5
6
7
a Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of new pyrazole oximes bearing substituted thiazole ring were designed and prepared. The
structures of the title compounds were identified by spectral analyses. The results of primary bioassay
indicated that some targeted compounds exhibited promising insecticidal activity besides acaricidal
activity, particularly; compounds 8c and 8d were more potent against Tetranychus cinnabarinus and
Plutella xylostella than other analogues.
Received 15 May 2014
Received in revised form 26 May 2014
Accepted 30 May 2014
Available online xxx
ß 2014 Hong Dai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords:
Pyrazole oxime
Substituted thiazole
Acaricidal activity
Insecticidal activity
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1. Introduction
search for biologically active molecules bearing substituted 30
thiazole group.
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12
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14
15
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18
19
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During the past two decades, different classes of pyrazole oxime
compounds have been investigated and many of them are found to
possess broad spectrum of bioactivities such as fungicidal [1–3],
acaricidal [4], insecticidal [5], anti-TMV [6,7], antibacterial [8], and
anti-inflammatory activities [9]. For example, fenpyroximate (in
Fig. 1), a well-known agricultural acaricide bearing a pyrazole
oxime moiety in the structure, has been reported to exhibit strong
acaricidal activity against several phytophagous mites on diverse
crops [10]. As a result, pyrazole oxime containing heterocycles
became a focus of chemical and pharmaceutical research.
Moreover, thiazole derivatives due to their unique chemical
and structural properties have drawn much attention recently
and are widely used in the fields of pesticides and medicines. Some
thiazole compounds were also synthesized as potential insecti-
cides [11,12] and fungicides [13]. Some thiazole-containing
derivatives also showed plant growth regulatory [14], herbicidal
[15], antimicrobial [16], and anti-inflammatory [17] activities.
Recently, Wang et al. [18] reported that some 2-cyanoacrylate
Inspired by these facts, we envisioned that the introduction of 32
the highly substituted thiazole moiety to the parent pyrazole 33
oxime scaffold might afford some new compounds (Fig. 1) 34
possessing wide spectrum bioactivities such as acaricidal and 35
insecticidal activity. We report herein the synthesis and biological 36
evaluation of
a variety of novel pyrazole oximes carrying 37
substituted thiazole unit.
38
2. Experimental
39
The synthetic route for the targeted compounds is shown in 40
Scheme 1. Starting from 2-chloro-5-chloromethylthiazole 1, 41
intermediates 2, 3, 4 were prepared in good yields according to 42
the reported protocols [18]. Intermediate 5 was conveniently 43
obtained by
intermediate aldehyde
a
similar method in the literature [19]. The 44
was successively synthesized via 45
6
the reaction of the corresponding aldehyde 5 with the respective 46
substituted phenols or 2-naphthalenol [19,20]. Compound 6 was 47
further converted to the oxime 7 by a reaction with hydroxylamine 48
hydrochloride using potassium hydroxide as a base. Finally, 49
treatment of oxime 7 with the key intermediate 4 under basic 50
conditions afforded the desired compounds 8a–8o in satisfactory 51
yields. Optimized reaction conditions were adopted to synthesize a 52
class of new pyrazole oxime derivatives containing substituted 53
thiazole moiety. Their biological activity against Tetranychus 54
cinnabarinus and Plutella xylostella was evaluated according to 55
Q3 compounds carrying
a
benzenyloxy-linked thiazole unit
displayed good bioactivities. This gave a great impetus to the
*
Corresponding author at: Shanghai Key Laboratory of Chemical Biology, School
Q2
of Pharmacy, East China University of Science and Technology, Shanghai 200237,
China.
E-mail address: daihong_2001@yahoo.com.cn (H. Dai).
the method described in literature [21–23].
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http://dx.doi.org/10.1016/j.cclet.2014.06.011
1001-8417/ß 2014 Hong Dai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Please cite this article in press as: H. Dai, et al., The thiazoylmethoxy modification on pyrazole oximes: Synthesis and insecticidal
biological evaluation beyond acaricidal activity, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.06.011

G Model
CCLET 3044 1–3
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H. Dai et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
Fig. 1. Strategic design of the title compounds.
Scheme 1. Reagents and conditions: (a) p-hydroxybenzaldehyde, potassium carbonate, ethanol, reflux for 8 h; (b) NaBH4 (2.0 equiv.), ethanol, 0 8C for 1 h, r.t. for 2 h; (c)
thionyl chloride (1.5 equiv.), dichloromethane, 0 8C for 30 min, r.t. for 12 h; (d) substituted phenols or 2-naphthalenol, potassium hydroxide, DMF, 40 8C for 2 h, 110 8C for 4–
12 h; (e) hydroxylamine hydrochloride, potassium hydroxide, methanol, reflux for 6–12 h; (f) potassium carbonate, acetonitrile, reflux for 8–24 h.
57
3. Results and discussion
CH55N protons, respectively. In the 13C NMR spectrum of 8a, the
peak belonging to CH55N group is observed at 152.7. The
biological activity data are listed in Table 1. Fenpyroximate was
used as a positive control. As shown in Table 1, some designed
compounds displayed promising acaricidal activity against T.
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71
72
73
74
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76
77
78
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80
81
d
58
59
60
61
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All the final derivatives 8a–8o were purified by column
chromatography on silica gel with the solvent system of ethyl
acetate and petroleum ether (60–90 8C), and their structures were
fully identified by 1H NMR, 13C NMR and elemental analysis. The
details are given in Supporting information. The 1H NMR spectrum
of 8a showed a singlet peak at
protons at the 3-position of the pyrazole ring. A singlet at
due to the methyl protons at the 1-position of the pyrazole ring.
Two singlets appeared in 5.14 and 4.93 ppm are due to the two
methylene protons in the molecule. The presence of two singlet
cinnabarinus at a concentration of 200
mg/mL. For example,
compounds 8c, 8d, and 8i achieved around 90% inhibition against
T. cinnabarinus, which was comparable to that of the control
Fenpyroximate. Additionally, compounds 8c, 8d, 8i and 8j showed
moderate to good inhibition against T. cinnabarinus when the
d
2.37 attributed to the methyl
3.58 is
d
dosage was reduced to 100
designed compounds were also active against P. xylostella at the
concentration of 200 g/mL. Among them, compounds 8b, 8c, 8d,
mg/mL. Encouragingly, some of the
signals at
d
7.51 and 7.78 are assignable to thiazole-4-CH and
m
Please cite this article in press as: H. Dai, et al., The thiazoylmethoxy modification on pyrazole oximes: Synthesis and insecticidal
biological evaluation beyond acaricidal activity, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.06.011

G Model
CCLET 3044 1–3
H. Dai et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
3
Table 1
Acaricidal and insecticidal activities of compounds 8a–8o (mortality, %).
Compounds
R
T. cinnabarinus
P. xylostella
200
mg/mL
100
m
g/mL
200
m
g/mL
100 mg/mL
8a
Phenyl
0
0
–
–
33
86
100
100
0
0
71
57
71
–
8b
3-Fluorophenyl
4-Fluorophenyl
4-Chlorophenyl
2-Bromophenyl
4-Bromophenyl
3-Nitrophenyl
8c
95
90
0
80
80
–
8d
8e
8f
50
0
0
71
32
27
86
57
0
0
8g
–
0
8h
2-Methylphenyl
3-Methylphenyl
4-Methylphenyl
4-Tert-butylphenyl
6-Chloro-3-methylphenyl
2,3-Dimethylphenyl
2,4-Difluorophenyl
2-Naphthyl
0
–
0
8i
90
80
0
70
50
–
43
0
8j
8k
–
8l
0
–
0
–
8m
0
–
0
–
8n
0
–
0
–
8o
0
–
0
–
Fenpyroximate
100
100
–
–
‘‘–’’ refers to ‘‘not tested’’.
[3] P.L. Zhao, L. Wang, X.L. Zhu, et al., Subnanomolar inhibitor of cytochrome bc1 120
82
83
84
85
86
87
88
89
90
91
92
93
and 8i displayed good to excellent insecticidal activity against P.
xylostella with inhibitory values of 86, 100, 100, and 86%,
respectively. Moreover, compounds 8b, 8c, and 8d had moderate
complex designed by optimizing interaction with conformationally flexible resi- 121
dues, J. Am. Chem. Soc. 132 (2010) 185–194.
122
[4] H.J. Song, Y.X. Liu, L.X. Xiong, et al., Design, synthesis, and insecticidal evaluation 123
of new pyrazole derivatives containing imine, oxime ether, and dihydroisoxazo- 124
line groups based on the inhibitor binding pocket of respiratory complex I, J. Agric. 125
insecticidal activity against P. xylostella at the dosage of 100
mg/
mL. The data presented in Table 1 also showed that 4-fluoro
substituted compound 8c and 4-chloro substituted analogue 8d
were more potent against T. cinnabarinus and P. xylostella than
other oxime derivatives. All the above data indicated that the
biological activity spectrums of pyrazole oxime derivatives were
significantly improved via the introduction of the substituted
thiazole moiety. These studies represent an important basis for the
development of novel pesticides in future.
Food Chem. 61 (2013) 8730–8736.
[5] X.M. Zou, M. Liu, H.Z. Yang, et al., Preparation of pyridine oxime ether derivatives 127
as pesticides and acaricides, CN 101659656, 2010.
126
128
[6] G.P. Ouyang, X.J. Cai, Z. Chen, et al., Synthesis and antiviral activities of pyrazole 129
derivatives containing an oxime moiety, J. Agric. Food Chem. 56 (2008) 10160– 130
10167.
131
[7] G.P. Ouyang, Z. Chen, X.J. Cai, et al., Synthesis and antiviral activity of novel 132
pyrazole derivatives containing oxime esters group, Bioorg. Med. Chem. 16 (2008) 133
9699–9707.
134
[8] L.S. Bai, Y. Wang, X.H. Liu, H.L. Zhu, B.A. Song, Novel dihydropyrazole derivatives 135
linked with multi(hetero)aromatic ring: synthesis and antibacterial activity, Chin. 136
Chem. Lett. 20 (2009) 427–430.
137
94
4. Conclusion
[9] R.R. Ranatunge, M. Augustyniak, U.K. Bandarage, et al., Synthesis and selective 138
cyclooxygenase-2 inhibitory activity of a series of novel, nitric oxide donor- 139
containing pyrazoles, J. Med. Chem. 47 (2004) 2180–2193.
[10] K. Motoba, H. Nishizawa, T. Suzuki, etal., Species-specificdetoxificationmetabolism 141
of fenpyroximate, a potent acaricide, Pestic. Biochem. Physiol. 67 (2000) 73–84.
140
95
96
97
98
In summary, we have achieved the synthesis of a series of new
pyrazole oxime derivatives bearing substituted thiazole moiety.
Preliminary bioassay demonstrated that some of the targeted
compounds possessed insecticidal property besides acaricidal
activity. Particularly, compounds 8c and 8d displayed relatively
good acaricidal activity against T. cinnabarinus and potential
insecticidal activity against P. xylostella at the testing concentra-
tions. Further structural modifications and bioactivity investiga-
tions on these new active compounds are currently in progress.
142
[11] P. Maienfisch, H. Huerlimann, A. Rindlisbacher, et al., The discovery of thia- 143
methoxam:
165–176.
a
second-generation neonicotinoid, Pest Manag. Sci. 57 (2001) 144
145
99
[12] H. Uneme, K. Iwanaga, N. Higuchi, et al., Synthesis and insecticidal activity of 146
100
101
102
103
nitroguanidine derivatives, Pestic. Sci. 55 (1999) 202–205.
[13] D.Y. Hu, B.A. Song, W. He, Progresses in the synthesis and biological activity of 148
thiazole derivatives, Chin. J. Synth. Chem. 14 (2006) 319–328.
147
149
[14] X. Qin, H.B. Yu, H. Dai, et al., Synthesis and plant-growth regulatory activities of 150
novel imine derivatives containing 1H-1,2,4-triazole and thiazole rings, Chin. 151
Chem. Lett. 21 (2010) 283–286.
152
[15] L.L. Jiang, Y. Tan, X.L. Zhu, et al., Design, synthesis, and 3D-QSAR analysis of novel 153
1,3,4-oxadiazol-2(3H)-ones as protoporphyrinogen oxidase inhibitors, J. Agric. 154
104
Acknowledgments
Food Chem. 58 (2010) 2643–2651.
155
105 Q4
106
107
108
109
This work was financial supported by the National Natural
Science Foundation of China (No. 21202089), China Postdoctoral
Science Foundation (No. 2013M531145), and the Research
Foundation of the Six People Peak of Jiangsu Province (No.
2013-SWYY-013).
[16] H.M. Refat, A.A. Fadda, Synthesis and antimicrobial activity of some novel 156
hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene 157
derivatives, Eur. J. Med. Chem. 70 (2013) 419–426.
158
[17] A. Zablotskaya, I. Segal, A. Geronikaki, et al., Synthesis, physicochemical characteri- 159
zation, cytotoxicity, antimicrobial, anti-inflammatory and psychotropic activity of 160
new
N-[1,3-(benzo)thiazol-2-yl]-w-[3,4-dihydroisoquinolin-2(1H)-yl]alkana- 161
mides, Eur. J. Med. Chem. 70 (2013) 846–856.
162
[18] T.T. Wang, G.F. Bing, X. Zhang, et al., Synthesis and herbicidal activities of 2-cyano- 163
3-benzylaminoacrylates containing thiazole moiety, Bioorg. Med. Chem. Lett. 20 164
110
Appendix A. Supplementary data
(2010) 3348–3351.
[19] H.J. Park, K. Lee, S.J. Park, et al., Identification of antitumor activity of pyrazole 166
oxime ethers, Bioorg. Med. Chem. Lett. 15 (2005) 3307–3312.
[20] T. Hideo, H. Hiroshi, N. Akira, et al., Pyrazole derivative and production thereof, 168
Japan Patent 62053970, 1987.
165
167
169
111
112
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2014.06.011.
[21] Y. Zhao, C.H. Mao, Y.Q. Li, et al., Synthesis, crystal structure, and insecticidal 170
activity of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole, J. Agric. Food 171
113
References
Chem. 56 (2008) 7326–7332.
172
114
115
116
117
118
119
[1] Y. Li, H.Q. Zhang, J. Liu, X.P. Yang, Z.J. Liu, Stereoselective synthesis and antifungal
activities of (E)-a-(methoxyimino)benzeneacetate derivatives containing 1,3,5-
substituted pyrazole ring, J. Agric. Food Chem. 54 (2006) 3636–3640.
[2] P.L. Zhao, F. Wang, M.Z. Zhang, et al., Synthesis, fungicidal, and insecticidal
activities of b-methoxyacrylate-containing N-acetyl pyrazoline derivatives, J.
Agric. Food Chem. 56 (2008) 10767–10773.
[22] Q.Q. Zhao, Y.Q. Li, L.X. Xiong, et al., Design, synthesis and insecticidal activity of 173
novel phenylpyrazoles containing a 2,2,2-trichloro-1-alkoxyethyl moiety, J. Agric. 174
Food Chem. 58 (2010) 4992–4998.
175
[23] A.H. Sayyed, J. Ferre, D.J. Wright, Mode of inheritance and stability of resistance to 176
Bacillus thuringiensis var kurstaki in a diamondback moth (Plutella xylostella) 177
population from Malaysia, Pest Manag. Sci. 56 (2000) 743–748.
178
Please cite this article in press as: H. Dai, et al., The thiazoylmethoxy modification on pyrazole oximes: Synthesis and insecticidal
biological evaluation beyond acaricidal activity, Chin. Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.06.011