Design, synthesis and bioactivities of novel dichloro-allyloxy-phenol-containing pyrazole oxime derivatives

Article abstract of DOI:10.3390/molecules201219811

In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by ¹H-NMR, ¹³C-NMR and elemental analysis. In addition, bioassays showed that all of the newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 μg/mL, and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm even at the dose of 20 μg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90% inhibition rates, respectively, which were comparable to that of the control pyridalyl.

Full text of DOI:10.3390/molecules201219811

Article
Design, Synthesis and Bioactivities of Novel
Dichloro-Allyloxy-Phenol-Containing Pyrazole
Oxime Derivatives
Hong Dai 1, Linyu Ye 1, Huiyang Zhuang 2, Baojiang Dai 3,*, Yuan Fang 1 and Yujun Shi 1,
*
Received: 10 November 2015 ; Accepted: 2 December 2015 ; Published: 8 December 2015
Academic Editor: Jean Jacques Vanden Eynde
1
College of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China;
dh123@ntu.edu.cn (H.D.); lyuye265@aliyun.com (L.Y.); fyuan6586@aliyun.com (Y.F.)
Nantong Nanshen Plant Protection Science and Technology Development Co. Ltd., Nantong 226017,
China; hyang6608@aliyun.com
School of Chemical and Biological Engineering, Nantong Vocational University, Nantong 226007, China
Correspondence: dbj20110802@163.com (B.D.); syj@ntu.edu.cn (Y.S.); Tel./Fax: +86-513-8105-0921 (B.D.);
+86-513-8501-2851 (Y.S.)
2
3
*
Abstract: In this study, in order to find novel biologically active pyrazole oxime compounds, a
number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized
according to the method of active group combination. All of the target compounds were confirmed
by 1H-NMR, 13C-NMR and elemental analysis. In addition, bioassays showed that all of the
newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and
low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them
displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 µg/mL,
and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm
even at the dose of 20 µg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90%
inhibition rates, respectively, which were comparable to that of the control pyridalyl.
Keywords: pyrazole oxime; dichloro-allyoxy-phenol; synthesis; biological activity
1. Introduction
Pyrazole oximes are an important class of heterocyclic compounds which have drawn intense
attention because of their good fungicidal [1,2], insecticidal [3–5], acaricidal [6], and anti-tobacco
mosaic virus (TMV) activity [7]. For instance, Fenpyroximate (Figure 1), a potent agricultural acaricide
with a vital pyrazole oxime backbone in the structure, possesses wonderful acaricidal property
against some phytophagous mites such as Polyphagotarsonemus latus Banks and Tetranychus urticae
Koch on different crops [8]. Since its appearance on the market in 1991, many chemists have begun to
study structural modification of Fenpyroximate. More recently, Zou and co-workers reported some
acaricidal and insecticidal Fenpyroximate analogues containing pyridine or thiazole group [9,10],
and Wang et al. obtained some acaricidal, insecticidal or fungicidal pyrazole oxime compounds by
replacing the substituted phenyl moiety of Fenpyroximate with oxazole ring [11]. Therefore, pyrazole
oxime group can be used as an important skeleton in exploring novel bioactive molecules.
Pyridalyl (Figure 1), a novel dichloro-allyloxy-phenol insecticide, was discovered by Sumitomo
Chemical Co., Ltd. and marketed in 2004 [12]. It displays good insecticidal activity against different
lepidopterous pests on various crops such as cotton and vegetables, and exhibits no cross-resistance
with other existing insecticides including synthetic pyrethroids, organic phosphates, benzoylureas
and nicotinic insecticides [13,14]. Its biochemical mode of action is still unknown, while recent study
Molecules 2015, 20, 21870–21880; doi:10.3390/molecules201219811
www.mdpi.com/journal/molecules

Molecules 2015, 20, 21870–21880
showed that pyridalyl can cause cell apoptosis in BM36 cells, and its insecticidal activities perhaps
be related to the generation of active oxygen species of a pyridalyl metabolite [15]. In the past few
years, a lot of biologically active dichloro-allyoxy-phenol-containing pyridalyl derivatives have been
found [16–19]. It has been demonstrated that the dichloro-allyloxy-phenol group is essential for the
activity of pyridalyl analogues [20,21].
O
CH3
CH3
O
CH3
O
Cl
H3C
N
O
O
Cl
n
N
H3C
N
O
N
R2 Cl
O
Cl
CH3
N
O
N
Fenpyroximate
R1
n= 1-3
R1= CH3, C6H5
R2= 2-F, 4-F, 4-Cl, 4-Br, 4-I, 4-CH3, 2,4-F2,etc.
Cl
O
O
N
Cl
Cl
O
Cl
F3C
Target molecules
Pyridalyl
Figure 1. The design of the target molecules.
Nowadays, owing to long-term use of traditional pesticides, several field populations of
plant pests have already developed high levels of insecticide resistance [22], which leads to
the great losses of crop production. Therefore, researchers have to search for novel, efficient,
and low toxicity insecticides. In view on the facts above, the authors sought to incorporate the
dichloro-allyloxy-phenol moiety into pyrazole oxime molecules by the intermediate derivatisation
method [23]. In the present work, a series of novel dichloro-allyloxy-phenol-containing pyrazole
oxime compounds were synthesized, and their acaricidal and insecticidal activities were
screened briefly.
2. Results and Discussion
2.1. Chemistry
As indicated in Scheme 1, 18 pyrazole oxime derivatives bearing dichloro-allyloxy-phenol
moiety were successfully synthesized. Using diethylamine as the catalyst, 4-(3,3-dichloroallyloxy)-
2,6-dichlorophenol (2) was obtained by the reaction of compound 1 with sulfonyl chloride in the
solvent of toluene. Then intermediate 2 was reacted with dibromoalkanes in DMF with potassium
carbonate as the base to form compound 3. 5-aryloxy substituted pyrazole aldehyde 5 was produced
by nucleophilic substitution of compound 4 with various substituted phenols under basic conditions.
Subsequently, pyrazole aldehyde 5 was smoothly converted to pyrazole oxime 6 by treatment with
hydroxylamine using potassium hydroxide as the base. Finally, the reaction of compound 6 with the
key intermediate 3 under potassium carbonate promoting conditions afforded the title compounds
7a–7r in good yields. The structures of all the target compounds were effectively determined by
1H-NMR, 13C-NMR and elemental analysis.
2.2. Biological Activities
The acaricidal activity against Tetranychus cinnabarinus and insecticidal activity and against
Oriental armyworm and Aphis craccivora of all target compounds were tested and the data were listed in
21871

Molecules 2015, 20, 21870–21880
Table 1. Fenpyroximate, Pyridalyl and Imidacloprid were used as the positive controls, respectively.
The linkage moiety between the pyrazole oxime and 1,1-dichloropropene were three (7a–7m), four
(7n–7p), and five (7q and 7r) carbon chains. As displayed in Table 1, all of the title compounds
possessed no activities against Tetranychus cinnabarinus at a concentration of 500 µg/mL, and most
of them showed lower activity against Aphis craccivora except compound 7q had 70% inhibition
rate at a dosage of 500 µg/mL. Encouragingly, most target compounds exhibited good larvicidal
activity against Oriental armyworm at a concentration of 500 µg/mL, which was comparable to that
of the control Pyridalyl. Moreover, some of the designed compounds displayed excellent larvicidal
activity against Oriental armyworm when the concentration was reduced to 100 µg/mL. For example,
compounds 7a, 7b, 7f, 7k, 7n, 7o, 7p, and 7q achieved 100% inhibition against Oriental armyworm.
Among them, compounds 7f, 7n, and 7p were still active against Oriental armyworm even when the
dosage was reduced to 20 µg/mL with inhibitory values of 100%, 90%, and 90%, respectively, which
were similar to that of the control Pyridalyl.
Cl
Cl
HO
HO
Cl
Br
O
Cl
Cl
Cl
a
n
b
O
Cl
O
Cl
Cl
3a-3c
O
Cl
1
2
n= 1-3
OH
O
O
H3C
N
H3C
H
H3C
H
R2
e
d
c
R2
N
N
O
Cl
N
N
N
O
N
R1
R1
R1
4
6
5
Cl
O
O
Cl
n
H3C
N
R2 Cl
O
Cl
N
O
N
R1
7a-7r
Scheme 1. Synthesis of the title compounds 7a–7r. Reagents and conditions: (a) sulfonyl chloride,
toluene, diethylamine, 60–65 ˝C for 4 h, 60% for 2; (b) BrCH2(CH2)nCH2Br, n = 1–3, potassium
carbonate, N,N-dimethylformamide (DMF), 0 ˝C for 1 h, r.t. for 5–8 h, 46%–55% for 3; (c) substituted
phenols, potassium hydroxide, DMF or dimethylsulfoxide (DMSO), 45 ˝C for 2 h, then 110 ˝C for
5–24 h, 56%–78% for 5; (d) hydroxylamine hydrochloride, potassium hydroxide, methanol or ethanol,
reflux for 4–18 h, 61%–82% for 6; (e) compounds 3a–3c, potassium carbonate, acetonitrile, reflux for
10–24 h, 52%–71% for 7.
From the data presented in Table 1, we found that the structure-activity relationships of the
aimed compounds were not very obvious. However, fluorinated derivatives showed relatively
better larvicidal activity against Oriental armyworm than other analogues. At the concentration
of 20 µg/mL, compounds 7f, 7n, 7o, 7p, and 7q had 100%, 90%, 60%, 90% and 50% inhibitory
effects against Oriental armyworm, respectively. When the carbon chain that links the pyrazole
oxime and dichloro-allyloxy-phenol moieties is three carbons, the 4-fluorosubstituted analogue
7f exhibited a higher insecticidal activity against Oriental armyworm than did the corresponding
2- and 3-substituted analogues (7d and 7e), and compounds 7d, 7e, and 7f displayed 0%,
40%, and 100% larvicidal activity against Oriental armyworm at the concentration of 100 µg/mL,
respectively. Based on the structure-potency data, we can also see that compound 7n with a
21872

Molecules 2015, 20, 21870–21880
1,4-butylenedioxy group is more active against Oriental armyworm than corresponding compound
7d owning a 1,3-propylenedioxy group. When the enlargement of the linkage mioety between
the dichloro-allyloxy-phenol and pyrazole oxime units is five carbons, compound 7q (R1 = CH3,
R2 = 4-F) exhibited better biological activities than compound 7r (R1 = C6H5, R2 = 4-F), and compound
7q displayed interesting insecticidal activity against Aphis craccivora beyond satisfactory larvicidal
activity against Oriental armyworm. All the above data implied that structural modification of
Fenpyroximate by dichloro-allyloxy-phenol moiety could give some new compounds possessing
good biological activities. To obtain more active derivatives, further analogue synthesis and structural
optimization are currently in progress.
Table 1. Insecticidal and acaricidal activities of compounds 7a–7r (mortality, %).
Oriental
armyworm
100
Aphis
craccivora
Tetranychus
cinnabarinus
500
Compd.
n
R1
R2
500
20
500
100
µg/mL µg/mL µg/mL µg/mL µg/mL
µg/mL
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
3
3
CH3 4-OCH3 100
100
100
50
0
40
100
0
0
—
0
0
0
0
—
0
0
0
0
0
0
0
20
0
0
0
20
0
0
0
0
0
70
0
—
100
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
20
—
—
100
—
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CH3 4-CH3
CH3 4-OCF3
100
80
CH3
CH3
CH3
CH3
CH3
CH3
CH3
2-F
3-F
4-F
2-Cl
4-Cl
4-Br
4-I
100
100
100
100
100
0
100
—
—
—
—
0
—
—
90
60
90
50
—
100
—
—
80
CH3 3-NO2
CH3 3-CF3
CH3 2,4-Cl2
100
80
70
100
0
—
100
100
100
100
—
100
—
—
CH3
CH3
CH3 2,4-F2
CH3
C6H5
2-F
4-F
100
100
100
100
—
4-F
4-F
0
Pyridalyl
Imidacloprid
Fenpyroximate
100
—
—
—
—
100
“—” refers to “not tested”.
3. Experimental Section
3.1. Chemistry
3.1.1. General Procedures
All reagents were chemically pure and solvents were dried according to standard methods.
1H-NMR and 13C-NMR spectra were obtained on a Bruker AV400 spectrometer (400 MHz, 1H;
100 MHz, 13C, Bruker, Billerica, MA, USA) in CDCl3 with tetramethylsilane as the internal
standard. The melting points were determined on an X-4 binocular microscope melting point
apparatus (Beijing Tech Instrument Co., Beijing, China) and are uncorrected. Elemental analyses
were determined on a Yanaco CHN Corder MT-3 elemental analyzer (Yanaco, Kyoto, Japan). The
reactions were monitored by analytical thin-layer chromatography (TLC) with ultraviolet (UV) light
and TLC was carried out on silica gel GF254
.
The intermediates 4-(3,3-dichloroallyloxy)phenol
(1) and 4-(3,3-dichloroallyloxy)-2,6-dichlorophenol (2) were obtained by literature methods [24].
21873

Molecules 2015, 20, 21870–21880
5-chloropyrazole aldehyde 4 and 5-aryloxypyrazole aldehyde 5 were synthesized according to a
reported procedure [25].
3.1.2. General Procedure for the Preparation of 3a–3c
To a stirred solution of intermediate 2 (20 mmol) in anhydrous DMF was added powered
˝
potassium carbonate (22 mmol) at room temperature, and the mixture was cooled to 0 C. To the
above mixture, was added dropwise a solution of various dibromoalkanes (20 mmol) in anhydrous
˝
DMF (15 mL). The resulting reaction mixture was stirred for another 50 min at 0 C, and for 3–6 h at
room temperature. The mixture was poured into water (150 mL) and extracted with ethyl acetate
(3 ˆ 50 mL). The organic layer was washed with saturated brine (3 ˆ 30 mL) and dried over
anhydrous MgSO4. The solvent was evaporated under reduced pressure, and the residue was
subjected to silica gel column chromatography with petroleum ether and ethyl acetate as an eluent to
afford the compounds 3a–3c, with the yields ranging from 46% to 55% [19].
3.1.3. General Procedure for the Preparation of 6a–6r
To a stirred solution of hydroxylamine hydrochloride (15 mmol) in methanol or ethanol was
added potassium hydroxide (20 mmol) in portions at room temperature. The mixture was stirred for
another 20 min. To the above mixture, was added intermediate 5 (10 mmol) in portions. The resulting
mixture was heated to reflux for 4–15 h. After cooling to room temperature, the reaction mixture
was poured into water (100 mL) and allowed to stand overnight. The precipitate was collected by
filtration and washed with water (3 ˆ 50 mL). The solid residue was recrystallized from ethanol to
produce the pyrazole oximes 6a–6r, with yields ranging from 61% to 82% [11].
3.1.4. General Procedure for the Preparation of 7a–7r
To a well-stirred solution of pyrazole oxime 6 (10 mmol) and powered potassium carbonate
(20 mmol) in anhydrous acetonitrile (25 mL) was added intermediate 3 (12 mmol) in one portion at
room temperature. The mixture was then heated to reflux for 10–24 h. On completion, the mixture
was poured into water (60 mL) and extracted with dichloromethane (3 ˆ 40 mL). The combined
organic layer was washed with 10% sodium carbonate solution (3 ˆ 20 mL) and then with water
(3 ˆ 20 mL) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure,
and the residue was separated by silica gel column chromatography with petroleum ether and ethyl
acetate as an eluent to afford the target compounds 7a–7r, with yields ranging from 52% to 71%. All 18
pyrazole oxime derivatives 7a–7r were novel and the physical and spectral data for these compounds
1
are listed below. H-NMR and 13C-NMR spectra are provided in the Supplementary Materials.
1-Methyl-3-methyl-5-(4-methyoxyphenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroa
llyoxy)-phenoxy]propyl}-oxime (7a): Yellow oil, yield 69%. 1H-NMR (CDCl3): δ 7.76 (s, 1H, CH=N),
6.82–6.86 (m, 6H, Ar-H), 6.11 (t, J = 6.4 Hz, 1H, C=CH-CH2O), 4.58 (d, J = 6.0 Hz, 2H, C=CH-CH2O),
4.24 (t, J = 6.4 Hz, 2H, CH2O-Ar), 4.01 (t, J = 6.4 Hz, 2H, CH2O-N=CH), 3.77 (s, 3H, Ar-OCH3), 3.61
(s, 3H, N-CH3), 2.37 (s, 3H, CH3), 2.07–2.13 (m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 155.8, 153.9,
150.7, 148.3, 146.8, 146.0, 140.4, 129.8, 124.6, 119.8, 116.4, 115.2, 114.9, 100.0, 70.7, 70.4, 65.5, 55.7, 34.2,
29.7, 14.8. Anal. Calcd for C25H25Cl4N3O5: C 50.95; H 4.28; N 7.13. Found: C 50.82; H 4.46; N 7.30.
1-Methyl-3-methyl-5-(4-methylphenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]propyl}-oxime (7b): Yellow oil, yield 71%. 1H-NMR (CDCl3): δ 7.77 (s, 1H, CH=N), 7.10 (d,
J = 8.8 Hz, 2H, Ar-H), 6.83 (s, 2H, Ar-H), 6.78 (d, J = 8.8 Hz, 2H, Ar-H), 6.11 (t, J = 6.4 Hz, 1H,
C=CH-CH2O), 4.58 (d, J = 6.0 Hz, 2H, C=CH-CH2O), 4.24 (t, J = 6.4 Hz, 2H, CH2O-Ar), 4.00 (t,
J = 6.4 Hz, 2H, CH2O-N=CH), 3.59 (s, 3H, N-CH3), 2.37 (s, 3H, CH3), 2.30 (s, 3H, Ar-CH3), 2.06–2.12
(m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 154.7, 153.9, 148.0, 146.8, 146.0, 140.4, 133.1, 130.6, 130.4,
129.8, 124.6, 115.2, 115.1, 100.3, 70.7, 70.4, 65.5, 34.2, 29.7, 20.6, 14.8. Anal. Calcd for C25H25Cl4N3O4:
C 52.38; H 4.40; N 7.33. Found: C 52.21; H 4.25; N 7.17.
21874

Molecules 2015, 20, 21870–21880
1-Methyl-3-methyl-5-(4-trifluoromethoxyphenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-
dichloroallyoxy)-phenoxy]propyl}-oxime (7c): Yellow oil, yield 66%. 1H-NMR (CDCl3): δ 7.70 (s, 1H,
CH=N), 7.09 (d, J = 8.8 Hz, 2H, Ar-H), 6.84 (d, J = 9.2 Hz, 2H, Ar-H), 6.75 (s, 2H, Ar-H), 6.03 (t,
J = 6.4 Hz, 1H, C=CH-CH2O), 4.50 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.12 (t, J = 6.4 Hz, 2H, CH2O-Ar),
3.91 (t, J = 6.4 Hz, 2H, CH2O-N=CH), 3.55 (s, 3H, N-CH3), 2.30 (s, 3H, CH3), 1.95–2.00 (m, 2H,
CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 148.7, 147.0, 146.3, 146.0, 139.6, 129.8, 128.1, 124.6, 124.0,
123.8, 115.5, 115.2, 100.5, 70.6, 70.5, 65.5, 34.1, 29.6, 14.5. Anal. Calcd for C25H22Cl4F3N3O5: C 46.68;
H 3.45; N 6.53. Found: C 46.53; H 3.62; N 6.38.
1-Methyl-3-methyl-5-(2-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]propyl}-oxime (7d): Yellow oil, yield 52%. H-NMR (CDCl3): δ 7.77 (s, 1H, CH=N), 7.15–7.20
(m, 1H, Ar-H), 7.00–7.07 (m, 2H, Ar-H), 6.76–6.85 (m, 3H, Ar-H), 6.11 (t, J = 6.4 Hz, 1H, C=CH-CH2O),
4.58 (d, J = 6.0 Hz, 2H, C=CH-CH2O), 4.20 (t, J = 6.4 Hz, 2H, CH2O-Ar), 3.98 (t, J = 6.4 Hz, 2H,
CH2O-N=CH), 3.67 (s, 3H, N-CH3), 2.36 (s, 3H, CH3), 2.03–2.09 (m, 2H, CH2CH2CH2); 13C-NMR
(CDCl3): δ 153.9, 153.2, 152.0 (d, J = 247 Hz), 147.2, 147.0, 146.0, 144.3, 144.2, 139.8, 129.8, 125.0, 124.6,
124.4 (d, J = 7 Hz), 117.1 (d, J = 18 Hz), 116.7, 115.2, 100.0, 70.6, 70.5, 65.5, 34.2, 29.6, 14.5. Anal. Calcd
for C24H22Cl4FN3O4: C 49.94; H 3.84; N 7.28. Found: C 49.82; H 4.03; N 7.45.
1-Methyl-3-methyl-5-(3-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]propyl}-oxime (7e): Yellow oil, yield 54%. H-NMR (CDCl3): δ 7.78 (s, 1H, CH=N), 7.23–7.29
(m, 1H, Ar-H), 6.78–6.82 (m, 3H, Ar-H), 6.63–6.69 (m, 2H, Ar-H), 6.11 (t, J = 6.4 Hz, 1H, C=CH-CH2O),
4.57 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.22 (t, J = 6.4 Hz, 2H, CH2O-Ar), 3.99 (t, J = 6.4 Hz, 2H,
CH2O-N=CH), 3.62 (s, 3H, N-CH3), 2.38 (s, 3H, CH3), 2.04–2.11 (m, 2H, CH2CH2CH2); 13C-NMR
(CDCl3): δ 158.7 (d, J = 241 Hz), 153.8, 152.6, 152.5, 147.5, 146.8, 145.9, 139.9, 129.7, 124.8, 124.5, 116.5,
116.4, 116.2, 115.1, 100.1, 70.5, 70.4, 65.4, 34.1, 29.6, 14.5. Anal. Calcd for C24H22Cl4FN3O4: C 49.94; H
3.84; N 7.28. Found: C 50.06; H 3.69; N 7.12.
1-Methyl-3-methyl-5-(4-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]propyl}-oxime (7f): Yellow oil, yield 62%. 1H-NMR (CDCl3): δ 7.78 (s, 1H, CH=N), 6.86–7.04
(m, 4H, Ar-H), 6.85 (s, 2H, Ar-H), 6.13 (t, J = 6.0 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.0 Hz, 2H,
C=CH-CH2O), 4.24 (t, J = 6.0 Hz, 2H, CH2O-Ar), 4.01 (t, J = 6.0 Hz, 2H, CH2O-N=CH), 3.63 (s, 3H,
N-CH3), 2.39 (s, 3H, CH3), 2.06–2.13 (m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 146.9, 146.3
(d, J = 250 Hz), 146.0, 136.7, 129.8, 125.0, 124.6, 116.6, 116.3, 115.2, 100.2, 70.6, 70.5, 65.5, 34.2, 29.7,
14.6. Anal. Calcd for C24H22Cl4FN3O4: C 49.94; H 3.84; N 7.28. Found: C 50.12; H 3.72; N 7.21.
1-Methyl-3-methyl-5-(2-chlorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]propyl}-oxime (7g): Yellow oil, yield 53%. H-NMR (CDCl3): δ 7.75 (s, 1H, CH=N), 7.44–7.46
(m, 1H, Ar-H), 7.03–7.18 (m, 2H, Ar-H), 6.83 (s, 2H, Ar-H), 6.69–6.71 (m, 1H, Ar-H), 6.11 (t, J = 6.4 Hz,
1H, C=CH-CH2O), 4.58 (d, J = 6.0 Hz, 2H, C=CH-CH2O), 4.20 (t, J = 6.4 Hz, 2H, CH2O-Ar), 3.98 (t,
J = 6.4 Hz, 2H, CH2O-N=CH), 3.65 (s, 3H, N-CH3), 2.37 (s, 3H, CH3), 2.03–2.09 (m, 2H, CH2CH2CH2);
13C-NMR (CDCl3): δ 153.9, 152.2, 147.1, 146.9, 146.0, 139.7, 130.9, 129.8, 128.0, 124.6, 124.5, 122.9,
121.2, 115.6, 115.2, 100.3, 70.6, 70.5, 65.5, 34.2, 29.7, 14.4. Anal. Calcd for C24H22Cl5N3O4: C 48.55; H
3.73; N 7.08. Found: C 48.36; H 3.90; N 7.19.
1-Methyl-3-methyl-5-(4-chlorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]propyl}-oxime (7h): Yellow oil, yield 61%. 1H-NMR (CDCl3): δ 7.77 (s, 1H, CH=N), 7.30 (d,
J = 9.6 Hz, 2H, Ar-H), 6.86–6.93 (m, 4H, Ar-H), 6.14 (t, J = 6.0 Hz, 1H, C=CH-CH2O), 4.61 (d, J = 5.6 Hz
,
2H, C=CH-CH2O), 3.97–4.25 (m, 4H, CH2O-Ar and CH2O-N=CH), 3.68 (s, 3H, N-CH3), 2.43 (s, 3H,
CH3), 2.02–2.10 (m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 154.0, 152.9, 146.2, 145.8, 144.9, 138.5,
129.3, 128.9, 128.7, 123.9, 123.5, 118.2, 115.7, 114.2, 99.5, 69.6, 69.5, 64.5, 33.2, 28.6, 13.3. Anal. Calcd
for C24H22Cl5N3O4: C 48.55; H 3.73; N 7.08. Found: C 48.71; H 3.55; N 6.92.
1-Methyl-3-methyl-5-(4-bromophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]propyl}-oxime (7i): Yellow oil, yield 65%. 1H-NMR (CDCl3): δ 7.79 (s, 1H, CH=N), 7.43 (d,
21875

Molecules 2015, 20, 21870–21880
J = 8.8 Hz, 2H, Ar-H), 6.80–6.85 (m, 4H, Ar-H), 6.14 (t, J = 6.4 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz
,
2H, C=CH-CH2O), 4.24 (t, J = 6.4 Hz, 2H, CH2O-Ar), 4.01 (t, J = 6.4 Hz, 2H, CH2O-N=CH), 3.63 (s,
3H, N-CH3), 2.39 (s, 3H, CH3), 2.05–2.12 (m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 156.7, 155.8,
153.9, 147.0, 146.0, 139.9, 139.3, 132.8, 129.8, 125.0, 124.6, 122.4, 117.1, 116.1, 115.2, 100.4, 70.6, 70.5,
65.5, 34.2, 29.7, 14.5. Anal. Calcd for C24H22BrCl4N3O4: C 45.17; H 3.47; N 6.58. Found: C 45.06; H
3.63; N 6.45.
1-Methyl-3-methyl-5-(4-iodophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]propyl}-oxime (7j): Yellow oil, yield 67%. 1H-NMR (CDCl3): δ 7.76 (s, 1H, CH=N), 7.60 (d,
J = 8.8 Hz, 2H, Ar-H), 6.83 (s, 2H, Ar-H), 6.68 (d, J = 8.8 Hz, 2H, Ar-H), 6.11 (t, J = 6.4 Hz, 1H,
C=CH-CH2O), 4.58 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.21 (t, J = 6.4 Hz, 2H, CH2O-Ar), 3.99 (t,
J = 6.4 Hz, 2H, CH2O-N=CH), 3.61 (s, 3H, N-CH3), 2.37 (s, 3H, CH3), 2.03–2.09 (m, 2H, CH2CH2CH2);
13C-NMR (CDCl3): δ 156.6, 153.9, 147.0, 146.9, 146.0, 139.8, 139.2, 138.8, 129.8, 125.0, 124.6, 119.7,
117.6, 115.2, 100.4, 86.4, 70.7, 70.5, 65.5, 34.2, 29.7, 14.5. Anal. Calcd for C24H22Cl4IN3O4: C 42.07; H
3.24; N 6.13. Found: C 42.26; H 3.05; N 6.01.
1-Methyl-3-methyl-5-(3-nitrophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]propyl}-oxime (7k): Yellow oil, yield 55%. H-NMR (CDCl3): δ 7.99 (d, J = 8.4 Hz, 1H, Ar-H),
7.80 (s, 1H, CH=N), 7.77 (s, 1H, Ar-H), 7.27–7.54 (m, 2H, Ar-H), 6.84 (s, 2H, Ar-H), 6.13 (t, J = 6.4 Hz,
1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.14 (t, J = 6.4 Hz, 2H, CH2O-Ar), 3.95 (t,
J = 6.4 Hz, 2H, CH2O-N=CH), 3.68 (s, 3H, N-CH3), 2.39 (s, 3H, CH3), 1.97–2.03 (m, 2H, CH2CH2CH2);
13C-NMR (CDCl3): δ 157.0, 153.9, 149.3, 147.3, 145.6, 139.4, 130.6, 129.7, 125.0, 124.6, 121.6, 118.5,
115.2, 110.8, 100.4, 70.6, 70.4, 65.5, 34.3, 29.6, 14.1. Anal. Calcd for C24H22Cl4N4O6: C 47.70; H 3.67; N
9.27. Found: C 47.85; H 3.53; N 9.38.
1-Methyl-3-methyl-5-(3-trifluoromethylphenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-
dichloroallyoxy)-phenoxy]propyl}-oxime (7l): Yellow oil, yield 57%. 1H-NMR (CDCl3): δ 7.80 (s, 1H,
CH=N), 7.38–7.48 (m, 2H, Ar-H), 7.22 (s, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 6.85 (s, 2H, Ar-H),
6.13 (t, J = 6.4 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.0 Hz, 2H, C=CH-CH2O), 4.19 (t, J = 6.4 Hz, 2H,
CH2O-Ar), 3.98 (t, J = 6.4 Hz, 2H, CH2O-N=CH), 3.66 (s, 3H, N-CH3), 2.41 (s, 3H, CH3), 2.00–2.06
(m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 156.7, 153.9, 147.1, 146.5, 146.0, 139.6, 139.5, 130.6, 129.8,
125.0, 124.8, 124.6, 120.4, 118.4, 115.2, 112.8, 100.5, 70.5, 70.4, 65.5, 34.3, 29.6, 14.3. Anal. Calcd for
C25H22Cl4F3N3O4: C 47.87; H 3.54; N 6.70. Found: C 47.69; H 3.73; N 6.52.
1-Methyl-3-methyl-5-(2,4-dichlorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{3-[2,6-dichloro-4-(3,3-dichloroa
llyoxy)-phenoxy]propyl}-oxime (7m): Yellow oil, yield 60%. 1H-NMR (CDCl3): δ 7.77 (s, 1H, CH=N),
7.48 (d, J = 2.4 Hz, 1H, Ar-H), 7.13–7.16 (m, 1H, Ar-H), 6.85 (s, 2H, Ar-H), 6.65 (d, J = 8.8 Hz, 1H,
Ar-H), 6.14 (t, J = 6.4 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.21 (t, J = 6.4 Hz,
2H, CH2O-Ar), 4.01 (t, J = 6.4 Hz, 2H, CH2O-N=CH), 3.67 (s, 3H, N-CH3), 2.37 (s, 3H, CH3), 2.05–2.09
(m, 2H, CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 151.0, 147.1, 146.5, 146.0, 144.5, 143.7, 139.5, 130.6,
129.8, 127.9, 125.0, 124.6, 123.7, 116.3, 115.2, 100.2, 70.6, 70.5, 65.5, 34.3, 29.6, 14.3. Anal. Calcd for
C24H21Cl6N3O4: C 45.89; H 3.37; N 6.69. Found: C 45.72; H 3.51; N 6.85.
1-Methyl-3-methyl-5-(2-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{4-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]-n-butyl}-oxime (7n): Yellow oil, yield 54%. H-NMR (CDCl3): δ 7.78 (s, 1H, CH=N), 7.04–7.22
(m, 3H, Ar-H), 6.86 (s, 2H, Ar-H), 6.78–6.82 (m, 1H, Ar-H), 6.14 (t, J = 6.0 Hz, 1H, C=CH-CH2O), 4.61
(d, J = 4.0 Hz, 2H, C=CH-CH2O), 3.94–4.06 (m, 4H, CH2O-Ar and CH2O-N=CH), 3.69 (s, 3H, N-CH3),
2.39 (s, 3H, CH3), 1.73–1.86 (m, 4H, CH2CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 153.2, 152.0 (d,
J = 247 Hz), 147.2, 147.0, 146.0, 144.3, 144.2, 139.8, 129.8, 125.0, 124.6, 124.4 (d, J = 7 Hz), 117.1 (d,
J = 18 Hz), 116.7, 115.2, 100.0, 73.5, 73.4, 65.5, 34.2, 26.5, 25.5, 14.4. Anal. Calcd for C25H24Cl4FN3O4:
C 50.78; H 4.09; N 7.11. Found: C 50.60; H 4.22; N 7.29.
1-Methyl-3-methyl-5-(4-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{4-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
1
phenoxy]-n-butyl}-oxime (7o): Yellow oil, yield 63%. H-NMR (CDCl3): δ 7.78 (s, 1H, CH=N), 6.87–7.04
21876

Molecules 2015, 20, 21870–21880
(m, 4H, Ar-H), 6.85 (s, 2H, Ar-H), 6.13 (t, J = 6.0 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz, 2H,
C=CH-CH2O), 4.07 (t, J = 6.0 Hz, 2H, CH2O-Ar), 3.95 (t, J = 6.0 Hz, 2H, CH2O-N=CH), 3.63 (s, 3H,
N-CH3), 2.39 (s, 3H, CH3), 1.79–1.89 (m, 4H, CH2CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 146.9,
146.3 (d, J = 250 Hz), 146.0, 136.7, 129.8, 125.0, 124.6, 116.7, 116.4, 115.2, 100.5, 73.6, 73.3, 65.5, 34.2,
26.5, 25.6, 14.4. Anal. Calcd for C25H24Cl4FN3O4: C 50.78; H 4.09; N 7.11. Found: C 50.95; H 3.92;
N 7.23.
1-Methyl-3-methyl-5-(2,4-difluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{4-[2,6-dichloro-4-(3,3-dichloroa
llyoxy)-phenoxy]-n-butyl}-oxime (7p): Yellow oil, yield 56%. 1H-NMR (CDCl3): δ 7.76 (s, 1H,
CH=N), 6.96–6.99 (m, 1H, Ar-H), 6.85 (s, 2H, Ar-H), 6.78–6.81 (m, 2H, Ar-H), 6.13 (t, J = 6.4 Hz,
1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 4.04 (t, J = 6.4 Hz, 2H, CH2O-Ar),
3.95 (t, J = 6.0 Hz, 2H, CH2O-N=CH), 3.69 (s, 3H, N-CH3), 2.36 (s, 3H, CH3), 1.84–1.92 (m, 4H,
CH2CH2CH2CH2); 13C-NMR (CDCl3): δ 153.9, 147.1, 147.0, 146.0, 139.4, 129.8, 124.9, 124.6, 117.5,
117.4, 115.2, 111.2, 110.9, 105.8, 105.6, 105.3, 99.8, 73.5, 73.3, 65.4, 34.2, 26.5, 25.5, 14.3. Anal. Calcd for
C25H23Cl4F2N3O4: C 49.28; H 3.80; N 6.90. Found: C 49.43; H 3.65; N 6.72.
1-Methyl-3-methyl-5-(4-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{5-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]-n-pentyl}-oxime (7q): Yellow oil, yield 61%. 1H-NMR (CDCl3z): δ 7.75 (s, 1H, CH=N),
6.98–7.02 (m, 2H, Ar-H), 6.83–6.88 (m, 4H, Ar-H), 6.12 (t, J = 6.0 Hz, 1H, C=CH-CH2O), 4.58 (d,
J = 6.0 Hz, 2H, C=CH-CH2O), 3.92–4.01 (m, 4H, CH2O-Ar and CH2O-N=CH), 3.61 (s, 3H, N-CH3),
2.37 (s, 3H, CH3), 1.80–1.84 (m, 2H, CH2), 1.53-1.67 (m, 4H, 2 ˆ CH2); 13C-NMR (CDCl3): δ 149.8,
146.9, 146.1, 139.7, 130.4, 129.8, 125.0, 124.6, 123.0, 119.7, 116.6, 116.5, 116.3, 115.2, 100.3, 73.8, 73.6,
65.5, 34.2, 29.8, 28.8, 22.3, 14.6. Anal. Calcd for C26H26Cl4FN3O4: C 51.59; H 4.33; N 6.94. Found: C
51.43; H 4.52; N 6.81.
1-Phenyl-3-methyl-5-(4-fluorophenoxy)-1H-pyrazole-4-carbaldehyde-O-{5-[2,6-dichloro-4-(3,3-dichloroallyoxy)-
phenoxy]-n-pentyl}-oxime (7r): Yellow oil, yield 57%. 1H-NMR (CDCl3): δ 7.82 (s, 1H, CH=N), 7.61
(d, J = 8.0 Hz, 2H, Ar-H), 7.27–7.41 (m, 3H, Ar-H), 6.90–7.00 (m, 4H, Ar-H), 6.86 (s, 2H, Ar-H), 6.13
(t, J = 6.4 Hz, 1H, C=CH-CH2O), 4.60 (d, J = 6.4 Hz, 2H, C=CH-CH2O), 3.95–4.01 (m, 4H, CH2O-Ar
and CH2O-N=CH), 2.50 (s, 3H, CH3), 1.84–1.88 (m, 2H, CH2), 1.57–1.72 (m, 4H, 2 ˆ CH2); 13C-NMR
(CDCl3): δ 159.9, 157.5, 153.8, 152.6, 148.4, 147.0, 146.1, 139.4, 137.4, 129.8, 129.2, 127.3, 124.6, 122.2,
116.8 (d, J = 8 Hz), 116.4 (d, J = 24 Hz), 115.2, 102.1, 74.0, 73.5, 65.5, 29.8, 28.8, 22.3, 14.9. Anal. Calcd
for C31H28Cl4FN3O4: C 55.79; H 4.23; N 6.30. Found: C 55.95; H 4.06; N 6.15.
3.2. Biological Tests
3.2.1. Bioassay Methods
All bioassays were performed on representative test organisms reared in the laboratory. The
˝
bioassay was repeated in triplicate at 25 ˘ 1 C. Assessments were made on a dead/alive basis, and
mortality rates were corrected using Abbott’s formula. Evaluations were based on a percentage scale
of 0–100, where 0 equals no activity and 100 equals total kill. For comparative purposes, the controls
Fenpyroximate, Pyridalyl and Imidacloprid were tested under the same conditions.
3.2.2. Acaricidal Activity against Tetranychus cinnabarinus
The acaricidal activities against Tetranychus cinnabarinus of the designed compounds were
evaluated using the reported procedure [26]. Sieva bean plants with primary leaves expanded to
10 cm were selected and cut back to one plant per pot. A small piece was cut from a leaf taken from
the main colony and placed on each leaf of the test plants. This was done about 2 h before treatment
to allow the mites to move over to the test plant and to lay eggs. The size of the piece was varied to
obtain about 60–100 mites per leaf. At the time of the treatment, the piece of leaf used to transfer the
mites was removed and discarded. The mite-infested plant were dipped in the test formulation for
21877

Molecules 2015, 20, 21870–21880
3 s with agitation and set in the hood to dry. Plants were kept for 48 h before the numbers of live and
dead adults were counted. The test was run three times and results were averaged.
3.2.3. Larvicidal Activity against Oriental Armyworm
The larvicidal activities of the title compounds against Oriental armyworm were evaluated by
foliar application [27]. About 2 mg of precisely weighed sample was dissolved in 50 µL DMF, and then
diluted with water to get a required solution from 500 µg/mL to 20 µg/mL. Individual corn leaves
were placed on moistened pieces of filter paper in Petri dishes. The leaves were then dipped in test
solution and allowed to dry. The dishes were infested with 10 third-instar oriental armyworm larvae.
Mortality was assessed 48 h after treatment. The test was run three times and results were averaged.
3.2.4. Insecticidal Activity against Aphis craccivora
Insecticidal activities of the target compounds were tested against Aphis craccivora by foliar
application [28]. About 60 aphids were transferred to the shoot with 3–5 fresh leaves of horsebean.
The shoot with aphids was cut and dipped into a required solution from 500 µg/mL to 100 µg/mL of
the tested compound for 2 s. After removing extra solutions on the leaf, the aphids were raised in the
˝
shoot at 25 C and 85% relative humidity for 48 h. Each experiment for one compound was triplicated.
4. Conclusions
In conclusion,
a
number of novel pyrazole oxime derivatives containing
dichloro-allyloxy-phenol unit were designed and synthesized. Their insecticidal and acaricidal
activities were tested. The results indicated that all of the target compounds showed no
activities against Tetranychus cinnabarinus at a concentration of 500 µg/mL. Interestingly, most
of the synthesized compounds displayed good larvicidal activity against Oriental armyworm at a
concentration of 500 µg/mL. Some of the title compounds possessed good larvicidal activity against
Oriental armyworm even when the concentration was lowered to 20 µg/mL, particularly, compounds
7f, 7n, and 7p had 100%, 90%, and 90% inhibitory rates against Oriental armyworm, respectively,
which were comparable to that of the control Pyridalyl. Among these compounds, compound 7q
displayed broad spectrum biological activities, it showed potential insecticidal activity against Aphis
craccivora besides good larvicidal activity against Oriental armyworm. Further structural optimization
and biological activities about these pyrazole oximes are well under way.
Supplementary Materials: Supplementary materials (1H-NMR and 13C-NMR spectra of pyrazole oxime
derivatives 7a–7r) can be accessed at: http://www.mdpi.com/1420-3049/20/12/19811/s1.
Acknowledgments: This work was funded by the National Natural Science Foundation of China (Nos. 21202089,
21372135), the Research Foundation of the Six People Peak of Jiangsu Province (No. 2013-SWYY-013), the
Technology Project Fund of Nantong City (Nos. AS2013002, CP12013002, AS2014011).
Author Contributions: B.D. designed the research; H.D., L.Y., H.Z. and Y.F. performed the research and analyzed
the data; Y.S. wrote the paper. All authors read and approved the final manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
3.
Li, Y.; Zhang, H.Q.; Liu, J.; Yang, X.P.; Liu, Z.J. Stereoselective synthesis and antifungal activities
of (E)-α-(methoxyimino)benzeneacetate derivatives containing 1,3,5-substituted pyrazole ring. J. Agric.
Food Chem. 2006, 54, 3636–3640. [CrossRef] [PubMed]
Zhao, P.L.; Wang, L.; Zhu, X.L.; Huang, X.Q.; Zhan, C.G.; Wu, J.W.; Yang, G.F. Subnanomolar inhibitor of
cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues. J. Am.
Chem. Soc. 2010, 132, 185–194. [CrossRef] [PubMed]
Chen, L.; Ou, X.M.; Mao, C.H.; Shang, J.; Huang, R.Q.; Bi, F.C.; Wang, Q.M. Synthesis
and bioassay evaluation of 1-(4-substituteddidene-aminooxymethyl)-phenyl-3-(2,6-difluorobenzoyl)ureas.
Bioorg. Med. Chem. 2007, 15, 3678–3683. [CrossRef] [PubMed]
21878

Molecules 2015, 20, 21870–21880
4.
Dai, H.; Li, Y.Q.; Du, D.; Qin, X.; Zhang, X.; Yu, H.B.; Fang, J.X. Synthesis and biological activities of
novel pyrazole oxime derivatives containing a 2-chloro-5-thiazolyl moiety. J. Agric. Food Chem. 2008, 56,
10805–10810. [CrossRef] [PubMed]
5.
6.
Shi, Y.J.; Wang, S.L.; He, H.B.; Li, Y.; Li, Y.; Fang, Y.; Dai, H. Synthesis and bioactivity of novel pyrazole
oxime ester derivatives containing furan moiety. Chin. J. Org. Chem. 2015, 35, 1785–1791. [CrossRef]
Dai, H.; Xiao, Y.S.; Li, Z.; Xu, X.Y.; Qian, X.H. The thiazoylmethoxy modification on pyrazole oximes:
Synthesis and insecticidal biological evaluation beyond acaricidal activity. Chin. Chem. Lett. 2014, 25,
1014–1016. [CrossRef]
7.
8.
9.
Ouyang, G.P.; Cai, X.J.; Chen, Z.; Song, B.A.; Bhadury, P.S.; Yang, S.; Jin, L.H.; Xue, W.; Hu, D.Y.; Zeng, S.
Synthesis and antiviral activities of pyrazole derivatives containing an oxime moiety. J. Agric. Food Chem.
2008, 56, 10160–10167. [CrossRef] [PubMed]
Swanson, M.B.; Ivancic, W.A.; Saxena, A.M.; Allton, J.D.; O’Brien, G.K.; Suzuki, T.; Nishizawa, H.;
Nokata, M. Direct photolysis of Fenpyroximate in a buffered aqueous solution under a xenon lamp.
J. Agric. Food Chem. 1995, 43, 513–518. [CrossRef]
Fu, C.R.; Pei, J.; Ning, Y.; Liu, M.; Shan, P.C.; Liu, J.; Li, Y.Q.; Hu, F.Z.; Zhu, Y.Q.; Yang, H.Z.; et al. Synthesis
and insecticidal activities of novel pyrazole oxime ether derivatives with different substituted pyridyl rings.
Pest Manag. Sci. 2014, 70, 1207–1214. [CrossRef] [PubMed]
10. Yang, Y.Z.; Lin, D.Y.; Fu, C.R.; Zou, X.M. Synthesis and biological evaluation of novel pyrazole oxime ether
derivatives containing chlorothiazole group and pyrimidine rings. Chin. J. Org. Chem. 2015, 35, 100–108.
[CrossRef]
11. Wang, S.L.; Shi, Y.J.; He, H.B.; Li, Y.; Li, Y.; Dai, H. Synthesis and bioactivity of novel pyrazole oxime
derivatives containing oxazole ring. Chin. Chem. Lett. 2015, 26, 672–674. [CrossRef]
12. Sakamoto, N.; Saito, S.; Hirose, T.; Suzuki, M.; Matsuo, S.; Izumi, K.; Nagatomi, T.; IKegami, H.; Umeda, K.;
Tsushima, K.; et al. The discovery of pyridalyl: A novel insecticidal agent for controlling lepidopterous
pests. Pest Manag. Sci. 2003, 60, 25–34. [CrossRef] [PubMed]
13. Saito, S.; Isayama, S.; Sakamoto, N.; Umeda, K. Insecticidal activity of pyridalyl: Acute and sub-acute
symptoms in Spodoptera litura larvae. J. Pestic. Sci. 2004, 29, 372–375. [CrossRef]
14. Isayama, S.; Saito, S.; Kuroda, K.; Umeda, K.; Kasamatsu, K. Pyridalyl, a novel insecticide potency and
insecticidal selectivity. Arch. Insect Biochem. Physiol. 2005, 58, 226–233. [CrossRef] [PubMed]
15. Powell, G.F.; Ward, D.A.; Prescott, M.C.; Spiller, D.G.; White, M.R.H.; Earley, F.G.P. The molecular action of
the novel insecticide, pyridalyl. Insect Biochem. Mol. Biol. 2011, 41, 459–469. [CrossRef] [PubMed]
16. Tian, H.K.; Shi, F.X.; Liu, T.; Ni, J.P.; Ma, H.J.; Yang, C.L. Synthesis and insecticidal activity of
dichloropropene derivatives containing a coumarin group. Chin. J. Pestic. Sci. 2009, 11, 421–426.
17. Wu, T.W.; Ma, H.J.; Tian, H.K.; Ni, J.P.; Yun, Z. Synthesis and insecticidal activity of
3-[2,6-dichloro-4-(3,3-dichloroallyloxy)phenoxy]propyl pyrazole-5-carboxylate derivatives.
Chin.
J.
Org. Chem. 2010, 30, 713–718.
18. Guan, A.Y.; Qin, Y.K.; Wang, J.F.; Li, B. Synthesis and insecticidal activity of novel dihalopropene derivatives
containing benzoxazole moiety: A structure-activity relationship study. J. Fluor. Chem. 2013, 156, 120–123.
[CrossRef]
19. Li, M.; Liu, C.L.; Zhang, J.; Wu, Q.; Hao, S.L.; Song, Y.Q. Design, synthesis, and structure-activity
relationship of novel insecticidal dichloro-allyloxy-phenol derivatives containing substituted pyrazol-3-ols.
Pest Manag. Sci. 2013, 69, 635–641. [CrossRef] [PubMed]
20. Feng, M.L.; Li, Y.F.; Zhu, H.J.; Ni, J.P.; Xi, B.B. Design, synthesis, insecticidal activity and structure-activity
relationship of 3,3-dichloro-2-propenyloxy-containing phthalic acid diamide structures. Pest Manag. Sci.
2012, 68, 986–994. [CrossRef] [PubMed]
21. Li, J.; Wang, Z.Y.; Wu, Q.Y.; Yang, G.F. Design, synthesis, and insecticidal activity of novel
1,1-dichloropropene derivatives. Pest Manag. Sci. 2015, 71, 694–700. [CrossRef] [PubMed]
22. Cao, G.; Han, Z. Tebufenozide resistance selected in Plutella xylostella and its cross-resistance and fitness
cost. Pest Manag. Sci. 2006, 62, 746–751. [CrossRef] [PubMed]
23. Guan, A.Y.; Liu, C.L.; Yang, X.P.; Dekeysers, M. Application of the intermediate derivatization approach in
agrochemical discovery. Chem. Rev. 2014, 114, 7079–7107. [CrossRef] [PubMed]
24. Li, Q.; Yu, H.B.; Guan, A.Y.; Liang, S.J.; Song, Y.Q.; Li, B. Synthesis and insecticidal activity of sulfinic esters
containing dichloropropene. Chin. J. Org. Chem. 2012, 32, 1736–1740. [CrossRef]
21879

Molecules 2015, 20, 21870–21880
25. Park, M.S.; Park, H.J.; Park, K.H.; Lee, K.I. Introduction of N-containing heterocycles into pyrazole by
nucleophilic aromatic substitution. Synth. Commun. 2004, 34, 1541–1550. [CrossRef]
26. Song, H.J.; Liu, Y.X.; Xiong, L.X.; Li, Y.Q.; Yang, N.; Wang, Q.M. Design, synthesis, and insecticidal
evaluation of new pyrazole derivatives containing imine, oxime ether, oxime ester, and dihydroisoxazoline
groups based on the inhibitor binding pocket of respiratory complex I. J. Agric. Food Chem. 2013, 61,
8730–8736. [CrossRef] [PubMed]
27. Chen, Q.C.; Xiong, L.X.; Luo, M.; Wang, J.; Hu, C.Y.; Zhang, X.; Yu, S.J.; Li, Y.H.; Sun, D.Q. Synthesis,
larvicidal activities and antifungal activities of novel chlorantraniliprole derivatives and their target in the
ryanodine receptor. Molecules 2015, 20, 3854–3867. [CrossRef] [PubMed]
28. Xu, R.B.; Xia, R.; Luo, M.; Xu, X.Y.; Cheng, J.G.; Shao, X.S.; Li, Z. Design, synthesis, crystal structures, and
insecticidal activities of eight-membered azabridge neonicotinoid analogues. J. Agric. Food Chem. 2014, 62,
381–390. [CrossRef] [PubMed]
Sample Availability: Samples of the compounds 7a–7r are available from the authors.
© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open
access article distributed under the terms and conditions of the Creative Commons by
Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
21880