Design, synthesis and insecticidal evaluation of aryloxy dihalopropene derivatives

Article abstract of DOI:10.1016/j.bmc.2015.09.030

Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical structures were confirmed by ¹H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated. The results of bioassays indicated that most of the compounds showed moderate to high activities at the tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity against P. xylostella at 6.25 mg/L, while pyridalyl showed 50% insecticidal activity at the same concentration. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control of P. xylostella at 75-150 g a.i./ha, and the mortality of P. xylostella for treatment with compound 10e at 75 g a.i./ha was equivalent to pyridalyl at 105 g a.i./ha.

Full text of DOI:10.1016/j.bmc.2015.09.030

Bioorganic & Medicinal Chemistry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Design, synthesis and insecticidal evaluation of aryloxy
dihaloropropene derivatives
⇑
Ji-Chun Yang, Miao Li, Qiao Wu, Chang-Ling Liu , Xiu-Hui Chang
State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Research Institute of Chemical Industry Co. Ltd, Shenyang 110021, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species and one of the most important
pest of cruciferous crops worldwide. Pyridalyl as a novel class of insecticides has good efficacy against
P. xylostella. On the basis of the commercial insecticide pyridalyl, a series of new aryloxy dihaloropropene
derivatives were designed and synthesized by using Intermediate Derivatization Methods. Their chemical
structures were confirmed by 1H NMR, high-resolution mass spectrum (HRMS), and single-crystal X-ray
diffraction analysis. The insecticidal activities of the new compounds against P. xylostella were evaluated.
The results of bioassays indicated that most of the compounds showed moderate to high activities at the
tested concentration, especially compounds 10e and 10g displayed more than 75% insecticidal activity
against P. xylostella at 6.25 mg/L, while pyridalyl showed 50% insecticidal activity at the same concentra-
tion. The field trials result of the insecticidal activities showed that compound 10e as a 10% emulsifiable
concentrate (EC) was effective in the control of P. xylostella at 75–150 g a.i./ha, and the mortality of
P. xylostella for treatment with compound 10e at 75 g a.i./ha was equivalent to pyridalyl at 105 g a.i./ha.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 29 June 2015
Revised 13 September 2015
Accepted 17 September 2015
Available online xxxx
Keywords:
Aryloxy dihaloropropene derivatives
Insecticidal activities
Structure–activity relationship
Intermediate Derivatization Methods (IDM)
1. Introduction
practical method.8–19 It is well-known that the aryloxyphenyl
derivatives have been widely used in agriculture. For example,
Plutella xylostella (P. xylostella) is one of the most destructive
insects of cruciferous plants throughout the word, and it has
develop resistance to every class insecticides, even has become
resistant to chlorantraniliprole (Chlorantraniliprole is a recently
introduced to the market insecticide with a new mode of action
targeting the ryanodine receptor and has high potency against sen-
sitive P. xylostella).1 Pyridalyl as a novel class of insecticides has a
novel but unknown mode of action with good control efficacy
against various lepidopterous and thysanopterous pests on cotton
and vegetables without phytotoxicity. It also appears to be differ-
ent from other existing insecticides because it controls populations
of Heliothis virescens (H. virescens) and P. xylostella which are resis-
tant to various currently used insecticides. Pyridalyl is also less
harmful than existing insecticides to various beneficial arthro-
pods.2,3 Therefore, we are interested in further modifying its chem-
ical structure.
pyriproxyfen,20 fenoxycarb,20 flufenoxuron,21 chlorfluazuron21
and cyhalothrin22 have been used as commercial insecticides,
haloxyfop-methyl23 and fluazifop-butyl23 as herbicides, famox-
adone24 as fungicide (Fig. 1). So the terminal group replacement
method was applied by introducing aryloxyphenyl to pyridalyl to
replace pyridinyl (moiety B, Fig. 2). A series of new dihalopropene
analog with the substituted aryloxyphenyl were synthesized and
bioassayed. The detailed syntheses, bioassays, and structure–activ-
ity relationships of these compounds are discussed below.
2. Results and discussion
2.1. Chemistry
The synthetic routes for all the intermediates and target com-
pounds were illustrated in Schemes 1–4. Starting from p-dihydrox-
ybenzene (1), the Intermediates 3a–3c were prepared by the
chlorination with sulfonyl chloride, which has been reported
before (Scheme 1).15,25–27
Two routes were used to synthesize the aryloxyphenols 6b–6m
and 7a–7k as shown in Scheme 2. Aryloxyphenols 6b–6f were
prepared by Baeyer–Villiger oxidation/hydrolysis of aryloxyben-
zaldehydes 5b–5f with m-chloroperoxybenzoic acid (m-CPBA) in
50–85% yield. The corresponding aryloxybenzaldehydes 5b–5f
Intermediate Derivatization Methods (IDM) is a useful approach
for agrochemical discovery: common intermediate method, termi-
nal group replacement method, and active compound derivatiza-
tion method.4–7 Among these three approaches, the terminal
group replacement method has been proven as an effective and
⇑
Corresponding author. Tel.: +86 24 85869078; fax: +86 24 85869137.
E-mail address: liuchangling@vip.163.com (C.-L. Liu).
http://dx.doi.org/10.1016/j.bmc.2015.09.030
0968-0896/Ó 2015 Elsevier Ltd. All rights reserved.
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2
J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
F
F
H
N
H
N
O
F3C
Cl
H
N
H
N
O
F3C
Cl
O
N
N
H
O
O
O
F
O
O
O
N
O
O
O
F
O
F
Cl
Cl
O
chlorfluazuron
fenoxycarb
flufenoxuron
O
pyriproxyfen
O
O
O
CN
O
Cl
N
N
H
F3C
C4H9
F3C
Cl
O
O
O
O
O
CF3
O
O
N
O
N
O
fluazifop-butyl
famoxadone
cyhalothrin
haloxyfop-methyl
Figure 1. Commercial aryloxyphenyl derivatives.
R2
R1
R3
A
O
Moiety A
Moiety B
Cl
R2
R3
R1
O
O
O
Cl
O
Cl
F3C
Cl
Cl
Cl
A
R4
O
O
O
N
R5
Cl
pyridalyl
compounds 9-10
Figure 2. Design of aryloxyphenyl compounds.
Cl
HO
HO
Cl
3a
R4=Cl, R5=H
Cl
ii
i
HO
OH
3b R4=H, R5=H
3c
R4
O
Cl
O
2
Cl
R4=Cl, R5=Cl
R5
1
3
Scheme 1. Synthesis of compounds 3. Reagents and conditions: (i) 1,1,1,3-tetrachloropropane, K2CO3, CH3OH, 50 °C, 6 h; (ii) di-n-butylamine, SO2Cl2 (3a 1.85–2 equiv, 3b
0.95–1 equiv, 3c 3 equiv), toluene, room temperature, 1–2 h, yield 70–90% (3a 70%, 3b 85%, 3c 90%).
R2
R3
R1
O
A
CHO
ii
i
5
4b-4f
X=OH
R2
R3
R1
O
OH
R2
R3
R1
X
iii
A
A
4
4g-4x X=Cl
6-7
Scheme 2. Synthesis of compounds 6–7. Reagents and conditions: (i) p-fluorobenzaldehyde, K2CO3, dimethylacetamide, reflux, 6–10 h; (ii) m-CPBA, CHCl3, room
temperature, 1–3 h; (iii) p-dihydroxybenzene, K2CO3, DMF, room temperature, 8–12 h.
were synthesized from phenols 4 (X = OH) and p-fluorobenzalde-
hyde under basic conditions with yields of 45–80%, while R2 was
1,3-dibromopropane under basic conditions, followed by conden-
sation with aryloxyphenols 6a–6m or 7a–7k to afford compounds
9a–9m, 10a–10q.
The tether between the two aromatic parts has also been exam-
ined with compound 12. This compound was previously reported
in the patent literature as an insecticide.32 Compound 12 was syn-
thesized by using the same synthetic procedure with pyridinyloxy
phenol 7e and 3-chloro-2-(chloromethyl)prop-1-ene and followed
by condensation with 8a (Scheme 4).
not strong electron-withdrawing groups and
A was carbon
atom.28,29 Aryloxyphenols 6g–6m and 7a–7k were synthesized
from p-dihydroxybenzene and chlorobenzenes or chloropyridines
4 under basic conditions with yields of 50–95%, while R2 was
strong electron-withdrawing groups or A=N.30,31
The target compounds 9a–9m, 10a–10q were synthesized
as shown in Scheme 3. Intermediates 3a–3c were reacted with
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J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
3
Cl
Cl
Cl
HO
R4
R2
R3
R1
O
O
O
Br
O
Cl
ii
Cl
i
Cl
O
Cl
A
R4
O
Cl
R4
O
Cl
R5
R5
3a R4=Cl, R5=H
3b R4=H, R5=H
3c R4=Cl, R5=Cl
R5
8a R4=Cl, R5=H
8b R4=H, R5=H
8c R4=Cl, R5=Cl
9a-9m, 10a-10q
3a-3c
8a-8c
Scheme 3. Synthesis of compounds 9a–9m, 10a–10q. Reagents and conditions: (i) 1,3-dibromopropane, K2CO3, DMF, room temperature, 1 h; (ii) 6 or 7, K2CO3, CH3CN, reflux,
1 h.
Cl
F3C
O
O
F3C
O
Cl
F3C
OH
Cl
ii
i
N
O
Cl
O
Cl
O
N
N
O
12
7e
11
Scheme 4. Synthesis of compound 12. Reagents and conditions: (i) 3-chloro-2-(chloromethyl)prop-1-ene, K2CO3, CH3CN, reflux, 4 h; (ii) 3a, K2CO3, CH3CN, reflux, 1 h.
Table 1
Insecticidal activity against P. xylostella of compounds 9a–9m, 10a–10k
Cl
R2
R3
R1
O
O
Cl
A
O
Cl
O
Cl
Compound
A
R1
R2
H
CH3
Cl
OCH3
CH3
Cl
NO2
CF3
NO2
CF3
CF3
CF3
NO2
H
R3
P. xylostella (% mortality at the
given concentration in mg/L)
100
10
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
10k
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
C-NO2
C-Cl
C-Cl
N
N
N
N
N
N
N
N
N
H
H
H
H
Cl
Cl
H
H
Cl
Cl
H
Cl
Cl
H
H
H
H
H
Cl
Cl
Cl
F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
90
67
60
92
17
77
77
75
67
12
75
54
0
10
48
35
33
0
5
65
0
25
10
22
0
0
95
90
95
85
100
84
100
92
90
100
80
100
23
53
55
82
100*
10
75*
70
10
0
Cl
NO2
CN
CF3
H
CF3
Cl
Cl
CH3
Cl
N
N
Cl
Cl
10
75
Pyridalyl
*
6.25 mg/L.
2.2. Biological activity and the structure–activity relationship
(4-methoxy) were prepared and evaluated according to the Topliss
method. However, they provided no significant gain in potency,
relative to compound 9a. More phenoxyphenyl compounds
(9e–9m) were prepared to investigate structure–activity relation-
ship, which were disubstituted, trisubstituted or substituted by
electron-withdrawing group. Although there were a few excep-
tional patterns, they had better insecticidal activity when R2 was
electron-withdrawing group such as CF3 and NO2. Isosteric
replacement of benzenes by CF3-substituted pyridines generally
led to a number of useful agrochemicals.34 So compounds 10e
Initially compound 9a was synthesized by introducing
phenoxyphenyl to replace pyridinyl of commercial insecticide
pyridalyl by using terminal group replacement method of IDM.
Although compound 9a displayed 90% insecticidal activity against
P. xylostella at 100 mg Lꢀ1, it was less potent than pyridalyl
(Table 1). Since the Topliss method has often been applied to mod-
ification of the substituent of the phenyl ring in optimization
strategies.33 The compounds 9c (4-chloro), 9b (4-methyl), 9d
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J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
Table 2
Table 5
Insecticidal activity against P. xylostella of compounds 10e, 10g, 10l–10o
Field trial results for compound 10e at Wuhan against P. xylostella in 2012
Compound
Rate (g a.i./ha)
Mortality at days after spraying
(%)
Cl
F3C
R1
O
O
O
Cl
1
3
7
10
N
R4
O
Cl
10% 10e EC
75
105
150
70.4
78.3
79.5
94.5
98.1
99.3
90.7
93.7
96.3
84.6
86.3
91.6
R5
Compound
R1
R4
R5
P. xylostella (% mortality at the
10% pyridalyl EC
105
79.4
95.3
92.5
84.3
given concentration in mg/L)
600
100
10
6.25
Moiety E
Moiety C
10e
10g
10l
10m
10n
10o
H
Cl
H
Cl
H
Cl
Cl
Cl
H
H
Cl
Cl
H
H
H
H
Cl
Cl
100
100
100
100
100
80
100
100
80
80
50
100
90
20
20
20
0
100
75
—
—
—
Cl
R2
R3
R1
O
O
X
O
Cl
A
R4
O
Cl
R5
30
100
—
50
Moiety D
Pyridalyl
100
75
and 10g were prepared by introducing 5-CF3-pyridyloxyphenyl
and 2-Cl-5-CF3-pyridyloxyphenyl to replace phenoxyphenyl of
compounds 9a–9m, which was important pharmacophore of
haloxyfop-methyl and fluazifop-butyl respectively. Compounds
10e and 10g showed 100% and 75% control against P. xylostella,
respectively, at 6.25 mg Lꢀ1, it was more potent than compounds
9a–9m. More compounds with other substitutional pyridinyloxy
were prepared in order to obtain compounds with much higher
activity. However, we were disappointed to find that extensive
variety of analogs (10a, 10b, 10c, 10d, 10f, 10h, 10i, 10j, 10k) were
significant losses in activity in Table 1. Although it is difficult to
construct a clear structure–activity relationship from the data
shown in Table 1, it can be concluded that the general trend in
insecticidal activity for the substituents of moiety C was that A:
N > CH; R2: CF3 > NO2 > CN > other.
For further studying the structure–activity relationship, A as N, R2 as
CF3 were maintained, R1 and moiety D were changed (Table 2).
Compounds 10e and 10g (R4 = Cl, R5 = H) showed better insecticidal
activity against P. xylostella than other compounds (R4 = R5 =
H > R4 = R5 = Cl) and commercial insecticide pyridalyl. The struc-
ture–activity relationship could be conjectured, which R1: H > Cl;
R4 = Cl, R5 = H > R4 = R5 = H > R4 = R5 = Cl. Following A as N, R2 as
CF3, R4 as Cl, R5 as H were maintained, carbon chain of moiety E
was changed as shown in Table 3. In our biological tests at 10 mg Lꢀ1
,
compound 10e (X = CH2, 100%) was better than compounds 12
(X = 1,1-vinyl, 20%) and it can be hypothesized that the introduction
of a carbon sp2 in the tether reducing the liberty degree has a detri-
mental effect on the insecticidal activity. However, more compounds
like the carbonyl equivalent (X = C@O) will be required to elaborate
further the hypothesis. Out of our research, compound 10e was iden-
tified as the molecule with the most insecticidal activity. It showed
better insecticidal activity in our test system against P. xylostella than
pyridalyl with 100% and 50% control respectively at 6.25 mg Lꢀ1
.
Table 3
Compound 10e was therefore tested in field conditions.
Insecticidal activity against P. xylostella of compounds 10e and 12
The field trial results of insecticidal activities of compound 10e
as a 10% emulsifiable concentrate (EC) carried out at Shenyang
(2011) and Wuhan (2012) are summarized in Tables 4 and 5,
respectively. The field trial results demonstrate an effective control
of P. xylostella at 75, 105 and 150 g a.i./ha. The mortality against P.
xylostella of compound 10e at 75 g a.i./ha was equivalent to the
treatment with pyridalyl at 105 g a.i./ha.
Cl
F3C
O
X
O
Cl
N
O
Cl
O
Cl
Compound
X
P. xylostella (% mortality at the
given concentration in mg/L)
100
10
6.25
3. Conclusion
10e
12
CH2
100
100
100
CH2
Using IDM, a series of dichloro-allyloxy-phenol derivatives were
synthesized by introducing substituted aryloxy phenyl moiety.
Among these compounds, the insecticidal activities of 10e and
10g against P. xylostella at 6.25 mg Lꢀ1 are more potent than that
of pyridalyl, especially compound 10e with much more potent
insecticidal activity against P. xylostella both in greenhouse test
and field trials. Compound 10e is a promising candidate for further
development. This study demonstrates the effectiveness of IDM
approach to the discovery of high bioactive compounds. More field
trials of compound 10e are in progress.
80
20
75
—
Pyridalyl
100
50
Table 4
Field trial results for compound 10e at Shenyang against P. xylostella in 2011
Compound
Rate (g a.i./ha)
Mortality at days after
spraying (%)
4. Experimental methods
4.1. Chemistry
1
3
7
10% 10e EC
75
105
150
86.0
93.4
90.4
98.7
97.0
97.9
97.6
97.8
97.9
All starting materials and reagents were commercially available
and used without further purification except as indicated. Melting
10% pyridalyl EC
105
95.1
97.0
94.9
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J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
5
points were determined on a Büchi melting point apparatus M-565
and were uncorrected. 1H NMR spectra were recorded with
Mercury 300 (Varian, 300 MHz) spectrometer with CDCl3 or
DMSO-d6 as the solvent and tetramethylsilane as the internal
standard. Liquid chromatography–mass spectra (LC–MS) analysis
was performed using the Agilent Technologies 6230 TOF LC/MS.
Petroleum ether used for column chromatography had a boiling
range of 60–90 °C. Chemical names were generated using Chem-
Draw Ultra (Cambridge Soft, version 14.0). Intermediates 3a–3c
and 8a–8c were prepared in our laboratory according to the
methods reported by Li et al.15,25–27 4-Phenoxyphenol 6a was com-
mercially available. Aryloxybenzaldehydes 5b–5f, aryloxyphenols
6b–6m and 7a–7k were prepared according to procedures
previously described.28–31
4.1.1.6. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(2,4-dich
lorophenoxy)-phenolxy)propoxy)benzene (9f).
Viscous oil;
yield 83%. 1H NMR (300 MHz, CDCl3): d ppm 6.77–6.92 (m, 9H),
6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.24 (t,
J = 6.3 Hz, 2H, OCH2), 4.17 (t, J = 5.7 Hz, 2H, OCH2), 2.26–2.31 (m,
2H, CH2). HRMS (ESI+) m/z calcd for C24H19Cl6O+4, 580.9414 [M
+H]+; found: 580.9421.
4.1.1.7. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(4-nitro-
phenoxy)-phenoxy)propoxy)benzene (9g).
Viscous oil; yield
68%. 1H NMR (300 MHz, CDCl3): d ppm 8.19 (d, J = 9.3 Hz, 2H),
6.95–7.02 (m, 6H), 6.85 (s, 2H), 6.12 (t, J = 6.3 Hz, 1H, CH), 4.59
(d, J = 6.3 Hz, 2H, OCH2), 4.29 (t, J = 6.0 Hz, 2H, OCH2), 4.17 (t,
J = 6.0 Hz, 2H, OCH2), 2.29–2.33 (m, 2H, CH2). HRMS (ESI+) m/z
calcd for C24H20Cl4NO+6, 558.0044 [M+H]+; found: 558.0057.
4.1.1. Generalsynthetic procedure for compounds 9a–9m, 10a–10q
Aryloxyphenols 6a–6m or 7a–7k (1 equiv), 8a–8c (1 equiv),
anhydrous potassium carbonate (1.5 equiv) were added to
100 mL of flask with acetonitrile (50 mL) in sequence, the reaction
mixture was then heated to reflux for 1 h. The reaction was
monitored by thin-layer chromatography (TLC). After the reaction
was completed, the reaction mixture was cooled to room temper-
ature, filtered, concentrated under reduced pressure and the resi-
due was purified via silica gel column chromatography (ethyl
acetate/petroleum ether = 1:30) to give the target compounds.
4.1.1.8. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(4-(trifluo-
romethyl)-phenoxy)phenoxy)propoxy)benzene (9h).
Viscous
oil; yield 78%. 1H NMR (300 MHz, CDCl3): d ppm 7.54 (d, J = 8.7 Hz,
2H), 6.93–7.02 (m, 6H), 6.84 (s, 2H), 6.12 (t, J = 6.3 Hz, 1H, CH), 4.59 (d,
J = 6.3 Hz, 2H, OCH2), 4.27 (t, J = 6.3 Hz, 2H, OCH2), 4.17 (t, J = 6.0 Hz,
2H, OCH2), 2.28–2.33 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C25H20Cl4-
F3O+4, 581.0068 [M+H]+; found: 581.0073.
4.1.1.9. 1,3-Dichloro-2-(3-(4-(2-chloro-4-nitrophenoxy)phenoxy)
propoxy)-5-((3,3-dichloroallyl)oxy)benzene (9i).
Viscous oil;
4.1.1.1. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-phenoxy
yield 63%. 1H NMR (300 MHz, CDCl3): d ppm 8.37 (d, J = 3.0 Hz, 1H),
6.98–7.06 (m, 4H), 6.84 (s, 2H), 6.78–6.82 (m, 1H), 6.11 (t, J = 6.3 Hz,
1H, CH), 4.59 (d, J = 6.3 Hz, 2H, OCH2), 4.29 (t, J = 6.3 Hz, 2H, OCH2),
4.17 (t, J = 6.0 Hz, 2H, OCH2), 2.29–2.33 (m, 2H, CH2). HRMS (ESI+)
m/z calcd for C24H19Cl5NO+6, 591.9655 [M+H]+; found: 591.9661.
phenoxy)-propoxy)benzene (9a).
Pale yellow oil; yield 79%.
1H NMR (300 MHz, CDCl3): d ppm 7.27–7.33 (m, 2H), 6.89–7.06
(m, 7H), 6.84 (s, 2H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J =
6.3 Hz, 2H, OCH2), 4.25 (t, J = 6.3 Hz, 2H, OCH2), 4.16 (t, J = 6.0 Hz,
2H, OCH2), 2.27–2.31 (m, 2H, CH2). HRMS (ESI+) m/z calcd for
C
24H21Cl4O+4, 513.0194 [M+H]+; found: 513.0199.
4.1.1.10. 1,3-Dichloro-2-(3-(4-(2-chloro-4-(trifluoromethyl)phe-
noxy)phenoxy)propoxy)-5-((3,3-dichloroallyl)oxy)benzene
4.1.1.2. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(p-toly-
(9j).
Viscous oil; yield 81%. 1H NMR (300 MHz, CDCl3): d ppm
loxy)phenoxy)-propoxy)benzene (9b).
Viscous oil; yield
7.75 (d, J = 2.4 Hz, 1H), 7.47 (d, J = 9.0 Hz, 1H), 6.97–7.07 (m, 5H),
6.85 (s, 2H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H,
OCH2), 4.09 (t, J = 6.0 Hz, 2H, OCH2), 3.71 (t, J = 6.6 Hz, 2H, OCH2),
2.34–2.38 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C25H19Cl5F3O4+,
614.9678[M+H]+; found: 614.9669.
81%. 1H NMR (300 MHz, CDCl3): d ppm 7.10 (d, J = 3.9 Hz, 2H),
6.84–6.96 (m, 8H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz,
2H, OCH2), 4.23 (t, J = 6.3 Hz, 2H, OCH2), 4.16 (t, J = 6.0 Hz, 2H,
OCH2), 2.34 (s, 3H, CH3), 2.26–2.31 (m, 2H, CH2). HRMS (ESI+) m/z
calcd for C25H23Cl4O+4, 527.0350 [M+H]+; found: 581.0357.
4.1.1.11. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(2-ni-
tro-4-(trifluoro-methyl)phenoxy)phenoxy)propoxy)benzene
(9k).
8.21 (s, 1H), 7.66 (d, J = 9.0 Hz, 1H), 6.98–7.07 (m, 5H), 6.84 (s, 2H),
6.11 (t, J = 6.3 Hz, 1H, CH), 4.59 (d, J = 6.3 Hz, 2H, OCH2), 4.29 (t,
J = 6.3 Hz, 2H, OCH2), 4.17 (t, J = 6.0 Hz, 2H, OCH2), 2.29–2.33 (m,
2H, CH2). HRMS (ESI+) m/z calcd for C25H19Cl4F3NO+6, 625.9918 [M
+H]+; found: 625.9926.
4.1.1.3. 1,3-Dichloro-2-(3-(4-(4-chlorophenoxy)phenoxy)propo
xy)-5-((3,3-di-chloroallyl)oxy)benzene (9c).
Viscous oil;
Viscous oil; yield 69%. 1H NMR (300 MHz, CDCl3): d ppm
yield 71%. 1H NMR (300 MHz, CDCl3): d ppm 7.24 (d, J = 4.5 Hz,
2H), 6.84–7.03 (m, 8H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d,
J = 6.3 Hz, 2H, OCH2), 4.25 (t, J = 6.3 Hz, 2H, OCH2), 4.16 (t,
J = 6.0 Hz, 2H, OCH2), 2.27–2.31 (m, 2H, CH2). HRMS (ESI+) m/z
calcd for C24H20Cl5O+4, 546.9804 [M+H]+; found: 546.9817.
4.1.1.12. 1,3-Dichloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroal-
lyl)oxy)phenoxy)-propoxy)phenoxy)-5-(trifluoromethyl)ben-
zene (9l).
ppm 7.66 (s, 2H), 6.78–6.85 (m, 6H), 6.11 (t, J = 6.3 Hz, 1H, CH),
4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.22 (t, J = 6.3 Hz, 2H, OCH2), 4.16
(t, J = 6.0 Hz, 2H, OCH2), 2.27 (m, 2H, CH2). HRMS (ESI+) m/z calcd
for C25H18Cl6F3O+4, 648.9288 [M+H]+; found: 648.9279.
4.1.1.4. 1,3-Dichloro-5-((3,3-dichloroallyl)oxy)-2-(3-(4-(4-meth-
oxyphenoxy)-phenoxy)propoxy)benzene (9d).
Viscous oil;
Viscous oil; yield 75%. 1H NMR (300 MHz, CDCl3): d
yield 73%. 1H NMR (300 MHz, CDCl3): d ppm 6.83–6.94 (m, 10H),
6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.23
(t, J = 6.3 Hz, 2H, OCH2), 4.15 (t, J = 6.0 Hz, 2H, OCH2), 3.79 (s, 3H,
OCH3), 2.26–2.30 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C25H23
Cl4O+5, 543.0299 [M+H]+; found: 543.0307.
4.1.1.13. 1,3-Dichloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroal-
lyl)oxy)phenoxy)-propoxy)phenoxy)-5-nitrobenzene
(9m).
ppm 8.30 (s, 2H), 6.76–6.89 (m, 6H), 6.85 (s, 2H), 6.11 (t,
J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.22 (t,
J = 6.3 Hz, 2H, OCH2), 4.14 (t, J = 6.0 Hz, 2H, OCH2), 2.25–2.29 (m,
2H, CH2). HRMS (ESI+) m/z calcd for C24H18Cl6NO+6 625.9265 [M
+H]+, found: 625.9271.
4.1.1.5. 5. 1,3-Dichloro-2-(3-(4-(2-chloro-4-methylphenoxy)
phenoxy)propoxy)-5-((3,3-dichloroallyl)oxy)benzene
(9e).
6.78–6.90 (m, 9H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H,
OCH2), 4.23 (t, J = 6.3 Hz, 2H, OCH2), 4.15 (t, J = 6.3 Hz, 2H, OCH2),
2.26–2.31 (m, 5H, CH2+CH3). HRMS (ESI+) m/z calcd for C25H22Cl5
O+4, 560.9960[M+H]+; found: 560.9971.
Viscous oil; yield 67%. 1H NMR (300 MHz, CDCl3): d
Viscous oil; yield 66%. 1H NMR (300 MHz, CDCl3): d ppm
Please cite this article in press as: Yang, J.-C.; et al. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.09.030

6
J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
4.1.1.14.
2-(4-(3-(2,6-Dichloro-4-((3,3-dichloroallyl)oxy)phe-
Viscous oil; yield
oil; yield 87%. 1H NMR (300 MHz, CDCl3): d ppm 7.97 (d, J = 6.0 Hz,
noxy)propoxy)-phenoxy)pyridine (10a).
1H), 7.77 (d, J = 6.0 Hz, 1H), 6.95–7.08 (m, 4H), 6.84 (s, 2H), 6.12 (t,
J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.26 (t, J = 6.3 Hz,
2H, OCH2), 4.16 (t, J = 6.0 Hz, 2H, OCH2), 2.28–2.31 (m, 2H, CH2).
HRMS (ESI+) m/z calcd for C23H18Cl6NO4+, 581.9367 [M+H]+; found:
581.9377.
81%. 1H NMR (300 MHz, CDCl3): d ppm 8.19 (d, J = 7.5 Hz, 1H),
7.66 (t, J = 8.5 Hz, 1H), 6.84–7.09 (m, 8H), 6.84 (s, 2H), 6.12 (t,
J = 6.0 Hz, 1H, CH), 4.59 (d, J = 6.0 Hz, 2H, OCH2), 4.26 (t,
J = 6.0 Hz, 2H, OCH2), 4.16 (t, J = 6.3 Hz, 2H, OCH2), 2.28–2.32 (m,
2H, CH2). HRMS (ESI+) m/z calcd for C23H20Cl4NO+4, 514.0146 M
+H]+; found: 514.0152.
4.1.1.22.
oxy)phenoxy)
(10i).
Pale yellow oil; yield 62%. 1H NMR (300 MHz, CDCl3):
ppm 7.90 (d, J = 6.0 Hz, 1H), 7.48–7.54 (m, 1H), 7.08 (d,
5-Chloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroallyl)
propoxy)phenoxy)-3-fluoropyridine
4.1.1.15.
oxy)phenoxy)-propoxy)phenoxy)pyridine
oil; yield 86%. 1H NMR (300 MHz, CDCl3):
J = 2.7 Hz, 1H), 7.61 (dd, J = 2.7, 8.7 Hz, 1H), 6.82–7.06 (m, 7H),
6.12 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.26 (t,
J = 6.3 Hz, 2H, OCH2), 4.16 (t, J = 6.3 Hz, 2H, OCH2), 2.28–2.32 (m,
2H, CH2). HRMS (ESI+) m/z calcd for C23H19Cl5NO+4, 547.9756 [M
+H]+; found: 547.9763.
5-Chloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroallyl)
(10b).
Viscous
d
d
ppm 8.12 (d,
J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 6.84 (s, 2H), 6.12 (t,
J = 6.3 Hz, 1H, CH), 4.59 (d, J = 6.3 Hz, 2H, OCH2),), 4.10–4.28 (m,
4H), 2.25–2.32 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C23H17Cl5-
FNO+4, 565.9662 [M+H]+; found: 565.9670.
4.1.1.23.
oxy)phenoxy)-propoxy)phenoxy)-5-methylpyridine
(10j).
Viscous oil; yield 68%. 1H NMR (300 MHz, CDCl3): d
3-Chloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroallyl)
4.1.1.16.
2-(4-(3-(2,6-Dichloro-4-((3,3-dichloroallyl)oxy)phe-
noxy)propoxy)-phenoxy)-5-nitropyridine
(10c).
Viscous
ppm 7.83 (s, 1H), 7.57 (s, 1H), 6.92–7.08 (m, 4H), 6.84 (s, 2H),
6.11 (t, J = 6.3 Hz, 1H, CH), 4.58 (d, J = 6.3 Hz, 2H, OCH2), 4.25 (t,
J = 6.3 Hz, 2H, OCH2), 4.16 (t, J = 6.0 Hz, 2H, OCH2), 2.27–2.31 (m,
2H, CH2), 2.26 (s, 3H, CH3). HRMS (ESI+) m/z calcd for C24H21Cl5NO4+,
561.9913 [M+H]+; found: 561.9925.
oil; yield 65%. 1H NMR (300 MHz, CDCl3):
d
ppm 9.06 (d,
J = 2.4 Hz, 1H), 8.46 (dd, J = 2.4, 9 Hz, 1H), 6.98–7.10 (m, 5H), 6.85
(s, 2H), 6.12 (t, J = 6.3 Hz, 1H, CH), 4.59 (d, J = 6.3 Hz, 2H, OCH2),
4.28 (t, J = 6.0 Hz, 2H, OCH2), 4.17 (t, J = 6.0 Hz, 2H, OCH2), 2.29–
2.33 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C23H19Cl4N2O+6,
558.9997 [M+H]+; found: 558.0017.
4.1.1.24.
dichloroallyl)oxy)-phenoxy)propoxy)phenoxy)pyridine
(10k).
Oil; yield 68%. 1H NMR (300 MHz, CDCl3): d ppm 7.89
2,3,5-Trichloro-6-(4-(3-(2,6-dichloro-4-((3,3-
4.1.1.17.
6-(4-(3-(2,6-Dichloro-4-((3,3-dichloroallyl)oxy)phe-
Viscous oil;
noxy)propoxy)-phenoxy)nicotinonitrile (10d).
(s, 1H), 687–7.21 (m, 4H), 6.84 (s, 2H), 6.12 (t, J = 6.3 Hz, 1H, CH),
4.59 (d, J = 6.3 Hz, 2H, OCH2), 4.00–4.28 (m, 4H), 2.25–2.36 (m,
2H). HRMS (ESI+) m/z calcd for C23H17Cl7NO+4, 615.8977 [M+H]+;
found: 615.8985.
yield 81%. 1H NMR (300 MHz, CDCl3): d ppm 8.47 (dd, J = 0.6,
2.4 Hz, 1H), 7.89 (dd, J = 2.4, 8.7 Hz, 1H), 6.97–7.08 (m, 5H), 6.84
(s, 2H), 6.11 (t, J = 6.3 Hz, 1H, CH), 4.59 (d, J = 6.3 Hz, 2H, OCH2),
4.27 (t, J = 6.3 Hz, 2H, OCH2), 4.16 (t, J = 6.0 Hz, 2H, OCH2), 2.28–
2.32 (m, 2H, CH2). HRMS (ESI+) m/z calcd for C24H19Cl4N2O+4,
539.0099 [M+H]+; found: 539.0106.
4.1.1.25. 2-(4-(3-(2-Chloro-4-((3,3-dichloroallyl)oxy)phenoxy)
propoxy)-phenoxy)-5-(trifluoromethyl)pyridine (10l).
Vis-
cous oil; yield 82%. 1H NMR (300 MHz, CDCl3): d ppm 8.46 (s,
1H), 7.88 (d, J = 8.7 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 6.95–6.98 (m,
3H), 6.90 (d, J = 9.0 Hz, 1H), 6.73–6.77 (m, 1H), 6.13 (t, J = 6.0 Hz,
1H), 4.59 (d, J = 6.0 Hz, 2H), 4.16–4.24 (m, 4H), 2.28–2.34 (m,
2H). HRMS (ESI+) m/z calcd for C24H20Cl4F3NO4+, 548.041 [M+H]+;
found: 548.0418.
4.1.1.18.
noxy)propoxy)-phenoxy)-5-(trifluoromethyl)pyridine
(10e).
White solid; yield 87%. Mp 68–70 °C. 1H NMR
(300 MHz, CDCl3): d ppm 8.45 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H),
7.07 (d, J = 9.0 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), 6.97 (d, J = 8.7 Hz,
1H), 6.84 (s, 2H), 6.11 (t, J = 6.3 Hz, 1H), 4.57 (d, J = 6.3 Hz, 2H),
4.27 (t, J = 6.0 Hz, 2H), 4.17 (t, J = 6.0 Hz, 2H), 2.26–2.32 (m, 2H).
HRMS (ESI+) m/z calcd for C24H19Cl4F3NO4+, 582.002 [M+H]+, found:
581.9999.
2-(4-(3-(2,6-Dichloro-4-((3,3-dichloroallyl)oxy)phe-
4.1.1.26. 3-Chloro-2-(4-(3-(2-chloro-4-((3,3-dichloroallyl)oxy)
phenoxy)propoxy)phenoxy)-5-(trifluoromethyl)pyridine
(10m).
Viscous oil; yield 79%. 1H NMR (300 MHz, CDCl3): d
ppm 8.26 (s, 1H), 7.96 (s, 1H), 7.09 (d, J = 9.0 Hz, 2H), 6.95–6.99
4.1.1.19.
3-Chloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroallyl)
(10f). Viscous
oxy)phenoxy)-propoxy)phenoxy)pyridine
oil; yield 67%. 1H NMR (300 MHz, CDCl3): d ppm 8.02 (dd, J = 1.5,
4.8 Hz, 1H), 7.74 (dd, J = 1.5, 7.5 Hz, 1H), 7.10 (d, J = 2.4 Hz, 2H),
6.91–6.98 (m, 3H), 6.84 (s, 2H), 6.12 (t, J = 6.3 Hz, 1H, CH), 4.58
(d, J = 6.3 Hz, 2H, OCH2), 4.26 (t, J = 6.3 Hz, 2H, OCH2), 4.16 (t,
J = 6.3 Hz, 2H, OCH2), 2.28–2.32 (m, 2H, CH2). HRMS (ESI+) m/z
calcd for C23H19Cl5NO+4, 547.9756 [M+H]+; found: 547.9768.
4.1.1.20.
oxy)phenoxy)-propoxy)phenoxy)-5-(trifluoromethyl)pyridine
(10g).
Pale yellow oil; yield 84%. 1H NMR (300 MHz, CDCl3): d
3-Chloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroallyl)
ppm 8.27 (s, 1H), 7.96 (s, 1H), 7.10 (d, J = 9.0 Hz, 2H), 6.98 (d,
J = 9.0 Hz, 2H), 6.84 (s, 2H), 6.11 (t, J = 6.3 Hz, 1H), 4.58 (d,
J = 6.3 Hz, 2H), 4.28 (t, J = 6.0 Hz, 2H), 4.17 (t, J = 6.0 Hz, 2H), 2.31
(m, 2H). HRMS (ESI+) m/z calcd for C24H18Cl5F3NO+4, 615.9630 [M
+H]+; found: 615.9623.
4.1.1.21. 3,5-Dichloro-2-(4-(3-(2,6-dichloro-4-((3,3-dichloroal-
lyl)oxy)phenoxy) propoxy)phenoxy)pyridine (10h).
Viscous
Figure 3. Crystal structure of compound 10e.
Please cite this article in press as: Yang, J.-C.; et al. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.09.030

J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
7
Table 6
Crystallographic data and structure refinement parameters for 10e
Formula
Molecular mass
T (K)
Crystal system
Space group
a (Å)
C24H18Cl4F3NO4
583.19
113(2)
Monoclinic
P2(1)/C
8.777(2)
8.0042(18)
35.670(8)
90.00
c
(deg)
90.00
2504.9(10)
4
1.546
0.528
1184
22,252
5991 [R(int) = 0.0515]
R1 = 0.0458, wR2 = 0.1205
R1 = 0.0578, wR2 = 0.1355
Volume (Å3)
Z
Calculated density (g/cm3)
Absorption coefficient (mmꢀ1
F(000)
)
b (Å)
c (Å)
Reflections collected
Independent reflections
Final R indices [I > 2
a
(deg)
r(I)]
b (deg)
91.759(4)
R indices (all data)
(m, 3H), 6.90 (d, J = 9.0 Hz, 1H), 6.73–6.77 (m, 1H), 6.13 (t,
J = 6.0 Hz, 1H), 4.59 (d, J = 6.3 Hz, 2H), 4.16–4.24 (m, 4H), 2.28–
2.32 (m, 2H). HRMS (ESI+) m/z calcd for C24H19Cl4F3NO+4, 582.002
[M+H]+; found: 582.0018.
radiation (k = 0.71073 Å) on a Bruker SMART 1000 CCD diffraction
meter. The data was corrected for Lorentz and polarization factors
and for absorption by using empirical scan data. The structure was
solved with the SHELX program, and refined by full-matrix least-
squares methods based on F2, with anisotropic thermal parameters
for the non-hydrogen atoms. The hydrogen atoms were located
theoretically and not refined. Crystallographic data and structure
refinement parameters are listed in Table 6.
4.1.1.27. 2-(4-(3-(2,3,6-Trichloro-4-((3,3-dichloroallyl)oxy)phe-
noxy)propoxy)-phenoxy)-5-(trifluoromethyl)pyridine
(10n).
Viscous oil; yield 76%. 1H NMR (300 MHz, CDCl3): d
ppm 8.45 (s, 1H), 7.89 (d, J = 9.0 Hz, 1H),7.08 (d, J = 9.0 Hz, 2H),
6.96–6.99 (m, 3H), 6.89 (s, 1H), 6.18 (t, J = 6.3 Hz, 1H), 4.69 (d,
J = 6.3 Hz, 2H), 4.27 (t, J = 6.3 Hz, 2H), 4.18 (t, J = 6.0 Hz, 2H),
2.28–2.36 (m, 2H). HRMS (ESI+) m/z calcd for C24H18Cl5F3NO+4,
615.963 [M+H]+; found: 615.9639.
4.3. Insecticidal assay
4.3.1. Greenhouse test
Each of the test compounds was first dissolved in a mixture of
acetone and water, and water containing 0.1% Tween 80 was then
added to make the stock solution. Serial test solutions were pre-
pared by using acetone and water (v/v = 9:1). Cabbage leaves were
dipped into test solutions prepared above for 5 s. After drying, each
leaf was put into a polyethylene cup, then infested with 5–10 3rd-
instar larvae and kept at 25 °C in observation room. Mortality was
assessed 3 days after treatment. The test results of the insecticidal
activities of the title compounds against P. xylostella are listed in
Tables 1–3. Biological data were presented from the range 0% (indi-
cates no mortality) to 100% (complete mortality).
4.1.1.28. 3-Chloro-2-(4-(3-(2,3,6-trichloro-4-((3,3-dichloroallyl)
oxy)phenoxy)-propoxy)phenoxy)-5-(trifluoromethyl)pyridine
(10o).
Viscous oil; yield 73%. 1H NMR (300 MHz, CDCl3): d
ppm 8.27 (s, 1H), 7.96 (s, 1H), 7.10 (d, J = 9.0 Hz, 2H), 6.99 (d,
J = 9.0 Hz, 2H), 6.89 (s, 1H), 6.18 (t, J = 6.3 Hz, 1H),4.69 (d,
J = 6.3 Hz, 2H), 4.28 (t, J = 6.3 Hz, 2H), 4.18 (t, J = 6.3 Hz, 2H),
2.28–2.34 (m, 2H). HRMS (ESI+) m/z calcd for C24H17Cl6F3NO+4,
649.9241 [M+H]+; found: 649.9253.
4.1.2. 2-(4-((2-((2,6-Dichloro-4-((3,3-dichloroallyl)oxy)phenoxy)
methyl)allyl)-oxy)phenoxy)-5-(trifluoromethyl)pyridine (12)
Anhydrous potassium tert-butoxide 2 g (17.5 mmol) and 3-
chloro-2-(chloromethyl)prop-1-ene 0.88 g (7 mmol) were added
to 100 mL of three-necked flask with DMF (20 mL) in sequence, a
solution of 4-(5-(trifluoromethyl)pyridin-2-yloxy)phenol (7e) 2 g
(7 mmol) in DMF (10 mL) was added dropwise to the above solu-
tion at room temperature, stirred for 2 h at this temperature, a
solution of 2,6-dichloro-4-((3,3-dichloroallyl)oxy)phenol (3a)
1.70 g (6.7 mmol) in DMF (10 mL) was added dropwise to the reac-
tion solution, and the reaction was monitored by thin-layer chro-
matography (TLC). After the reaction was completed, the mixture
was poured into water (200 mL) and extracted with ethyl acetate
(2 ꢁ 300 mL). The organic phases were combined, washed with
brine (2 ꢁ 200 mL), dried over anhydrous magnesium sulfate, con-
centrated under reduced pressure and the residue was purified via
silica gel column chromatography (ethyl acetate/petroleum
ether = 1:30) to give compound 12 (1.83 g, 46%) as a viscous oil.
1H NMR spectrum (300 MHz, internal standard TMS, solvent CDCl3)
is as follows: 8.44 (s, 1H), 7.88 (dd, J = 2.1, 8.7 Hz, 1H), 6.92–7.09
(m, 5H), 6.86 (s, 2H), 6.12 (t, J = 6.3 Hz, 1H), 5.48 (s, 2H), 4.78 (s,
2H), 4.58–4.60 (m, 4H). HRMS (ESI+) m/z calcd for C25H19Cl4F3NO4+,
594.002 [M+H]+; found: 594.0017.
4.3.2. Field trials against P. xylostella on cabbage
The trials were carried out in the test filed of Shenyang Research
Institute of Chemical Industry Ltd and Wuhan vegetable research
institute. The trial crop was cabbage (Variety: Zhonggan NO 8.).
The dosage of the compound 10e was 75, 105, 150 g a.i./ha and
comparative agent pyridalyl is 105 g a.i./ha. The application tool
was Shandongweishi WS-16P type backpack manual sprayer.
Evenly spraying to whole cabbage which is in rosette stage was
conducted. P. xylostella was originated at the peak time. The plot
area was 10 m2, 3 replicates and randomized block arrangement
were set. The amount of spray liquid was 750 L/ha. It was sunny
with the highest temperature of 29 °C, and the lowest of 17 °C on
the day of the application of the spray. The number of living larvae
was counted after 1 day, 3 days, 7 days and 10 days respectively
after application and control efficacy was calculated. Calculation
method:
Decrease rate of insectsð%Þ ¼ ðthe number of insects before application ꢀ the number
of insects after applicationÞ=the number of insects before application ꢁ 100
Control efficacyð%Þ ¼ ðdecrease rate of insects in treated area ꢀ decrease rate of insects
in blank comparative areaÞ=ð100 ꢀ decrease rate of insects in blank comparative areaÞ
ꢁ 100:
4.2. X-ray diffraction
Acknowledgements
Crystals of compound 10e were grown by a liquid–liquid diffu-
sion technique from a mixture of methanol and hexane (Fig. 3).
Crystallographic data was collected at 113 (2) K using Mo-Ka
The authors thank State Key Laboratory of Elemento-Organic
Chemistry of Nankai University for conducting X-ray Diffraction.
Please cite this article in press as: Yang, J.-C.; et al. Bioorg. Med. Chem. (2015), http://dx.doi.org/10.1016/j.bmc.2015.09.030

8
J.-C. Yang et al. / Bioorg. Med. Chem. xxx (2015) xxx–xxx
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Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.bmc.2015.09.030.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
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