Synthesis and Insecticidal Evaluation of Novel N-Oxalyl Derivatives of Tebufenozide

Article abstract of DOI:10.1021/jf048834e

A series of novel N'-tert-butyl-N'-3,5-dimethylbenzoyl-N-aryloxyoxalyl-N-4-ethylbenzoyl hydrazines containing a carboxylic acid or ester substituent on the aryl were synthesized, and their larvicidal activities were evaluated. The results of bioassays ind

Full text of DOI:10.1021/jf048834e

J. Agric. Food Chem. 2004, 52, 6737−6741 6737
Synthesis and Insecticidal Evaluation of Novel N-Oxalyl
Derivatives of Tebufenozide
CHUN HUI MAO,†,§ QING MIN WANG,*,† RUN QIU HUANG,† FU CHUN BI,†
†
LI CHEN,† YU XIU LIU,† AND JIAN SHANG
Research Institute of Elemento-Organic Chemistry, State Key Laboratory of Elemento-Organic
Chemistry, Nankai University, Tianjin 300071, People’s Republic of China, and
Hunan Branch of National Pesticide Research and Development South Center,
Changsha 410007, People’s Republic of China
A series of novel N ′-tert-butyl-N ′-3,5-dimethylbenzoyl-N-aryloxyoxalyl-N-4-ethylbenzoyl hydrazines
containing a carboxylic acid or ester substituent on the aryl were synthesized, and their larvicidal
activities were evaluated. The results of bioassays indicated that some of these title compounds
exhibit higher larvicidal activities than RH5849 (N-tert-butyl-N,N ′-dibenzoylhydrazine), but they are
not good compared to the parent compound (tebufenozide). The carboxylic acid substituent on the
aryl was essential for high larvicidal activity. Compared to the parent compound, these derivatives
displayed different physical properties, for example, better solubility in organic solvents. Toxicity assays
indicated that these derivatives could induce a premature, abnormal, and lethal larval molt.
KEYWORDS: N-Oxalyl derivative; tebufenozide; RH-5992; RH-5849; diacylhydrazine; larvicidal activity;
lethal larval molt; ecdysone
INTRODUCTION
solubility in water and limited solubility in common organic
solvents, and these disadvantages impede its field application
(8, 9).
Recently, synthetic substituted N′-tert-butyl-N,N′-diacylhy-
drazines have been found to work as nonsteroidal ecdysone
agonists inducing, especially in Lepidoptera, precocious molting,
leading to death (1-5). One of these, N-tert-butyl-N′-4-
ethylbenzoyl)-N-3,5-dimethylbenzoylhydrazide (tebufenozide;
RH-5992) (A), was the first to be commercialized as a
The activity spectrum of a pesticidal compound is often
determined by the physical properties of the compound, and it
is possible to convert a nonsystemic compound into one that is
systemic by attaching an appropriate functional group to an
insecticide. Moreover, the physical properties of an insecticidal
compound may be manipulated to obtain products with other
selected types of activity by proper selection of the derivatizing
moiety (10). In our previous work, the synthesis and insecticidal
evaluation of a series of novel N-sulfenylated derivatives of
diacylhydrazines have been reported, and the results of bioassay
showed that they exhibit excellent larvicidal activity, inducing
a premature, abnormal and lethal molting, and have better
solubility than the parent diacylhydrazines at the same time (9,
11, 12). Recently it was reported that N-oxalyl derivatives of
carbofuran containing a carboxylic acid or ester substituent (B)
displayed a wide spectrum of systemic pesticide activity
comparable or superior to that of carbofuran in the cut stem,
soil, and foliar applications. It was believed that the derivatives
containing a carboxylate moiety may result in compounds that
possibly have unusual systemic activity because carboxylic acid
groups are phloem mobile and may move downward as well as
upward in plants (13). Encouraged by these reports, we
developed an idea for the introduction of an aryloxy-
oxalyl containing a carboxylic acid or ester substituent into
N-tert-butyl-N′-4-ethylbenzoyl-N-3,5-dimethyl benzoylhydrazide
(tebufenozide). Therefore, in a search for new insect growth
regulators with improved profiles, we designed and synthesized
leptidopteran-specific insecticide under the trade names Mimic,
Confirm, and Romdan in several countries (6, 7). However,
tebufenozide does not have systemic action and has low
* Author to whom correspondence should be addressed [telephone +86-
(0)22-23504229; fax +86-(0)22-23503438; e-mail wang98h@263.net].
† State Key Laboratory of Elemento-Organic Chemistry.
§ Hunan Branch of National Pesticide Research and Development South
Center.
10.1021/jf048834e CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/07/2004

6738 J. Agric. Food Chem., Vol. 52, No. 22, 2004
Scheme 1. General Synthetic Route for Compounds III
Mao et al.
concentrated under reduced pressure to yield the compounds IVa-c
as a white solid.
Biological Assay. The larvicidal activities of the novel N-oxalyl
derivatives (IIIa-l, IVa-c), the parent compound (tebufenozide), and
RH-5849 (N-tert-butyl-N,N′-dibenzoylhydrazine) were evaluated using
a previously reported procedure (8, 9, 11, 12). The larvicidal activity
was tested against Oriental armyworm [Mythimna () Pseudaletia)
separata (Walker)] by foliar application. For the foliar armyworm tests,
individual corn leaves were placed on moistened pieces of filter paper
in Petri dishes. The leaves were then sprayed with the test solution
and allowed to dry. The dishes were infested with 10 fourth-instar
armyworm larvae. Percentage mortalities were evaluated 4 days after
treatment. Each treatment was performed in triplicate. Evaluations are
based on a percentage scale of 0-100 in which 0 equals no activity
and 100 equals total kill. Error of the experiments was 5%. For
comparative purposes, the parent compound (tebufenozide) was tested
under the same conditions. The larvicidal activity is summarized in
Table 3.
a series of novel N′-tert-butyl-N′-3,5-dimethylbenzoyl-N-aryl-
oxyoxalyl-N-4-ethylbenzoyl hydrazines containing carboxylic
acid or ester substituent derivatives on the aryl group (III and
IV) as shown in Schemes 1 and 2.
RESULTS AND DISCUSSION
Synthesis. N-tert-Butyl-N′-4-ethylbenzoyl-N-3,5-dimethyl-
benzoylhydrazide (A) was synthesized according to the reported
procedure (14). Substituted aryloxyoxalyl chlorides (II) were
prepared by the reaction of different hydroxybenzonate esters
(I) with oxalyl chloride in dichloromethane using pyridine as
the acid acceptor. Then the key intermediates were reacted
with N-tert-butyl-N′-4-ethylbenzoyl-N-3,5-dimethylbenzoyl-
hydrazide (A) in the dry THF using sodium hydride as alkali
to yield N′-tert-butyl-N′-3,5-dimethylbenzoyl-N-aryloxyoxalyl-
N-4-ethylbenzoyl hydrazines containing a carboxylate substitu-
ent (III) as shown in Scheme 1. The novel N-oxalyl derivatives
of tebufenozide containing carboxylic acid substituents (IV)
were synthesized by hydrogenation of the N′-tert-butyl-N′-3,5-
dimethylbenzoyl-N-benzyloxylcarbonylaryloxyoxalyl-N- 4-eth-
ylbenzoylhydrazines (IIId, IIIh, IIIl) in excellent yields using
palladium on carbon as catalyst as shown in Scheme 2. The
physical properties and elemental analyses of the new com-
pounds (IIIa-l, IVa-c) are listed in Table 1, and their 1H NMR
data are listed in Table 2.
First, we attempted to react N-tert-butyl-N′-4-ethylbenzoyl-
N-3,5-dimethylbenzoylhydrazide (A) with oxalyl chloride to
yield the corresponding N-oxalyl chloride, which was further
reacted with hydroxybenzonate esters (I) to yield the title
compounds III. We obtained 2-(3,5-dimethyl)phenyl-5-(4-ethyl)-
phenyl-1,3,4-oxadiazole instead of the N-oxalyl chloride of N′-
tert-butyl-N,N′-diacylhydrazines when compound A was treated
with oxalyl chloride in dichloromethane using pyridine as the
acid acceptor at room temperature. Under reflux in 1,2-
dichloroethane without pyridine, the reaction yielded 2-(3,5-
dimethyl)phenyl-5-(4-ethyl)-phenyl-1,3,4-oxadiazole and 4-tert-
butyl-2-(4-ethylphenyl)-4H-1,3,4-oxadiazine-5,6-dione at the
same time.
MATERIALS AND METHODS
General Synthetic Procedure for Substituted Aryloxyoxalyl
Chloride (II). To a mixture of hydroxybenzonate ester (I) (5.0 mmol)
and 10 mL of dry dichloromethane was added oxalyl chloride (7.5
mmol) in one portion. The mixture was chilled in an ice-water bath,
and pyridine (7.5 mmol) in 5 mL of dichloromethane was added
dropwise with stirring. After the addition of pyridine, the mixture was
stirred at room temperature for 30 min. Pyridine hydrochloride was
removed by filtration, and the filtrate was concentrated under vacuum.
Hexane (50 mL) was added to the residue, and the mixture was filtered
again to remove residual pyridine hydrochloride; hexane was removed
under vacuum to give substituted aryloxyoxalyl chloride (II) as a
colorless oily liquid, which was used for further operations without
purification.
General Synthetic Procedure for N′-tert-Butyl-N′-3,5-dimethyl-
benzoyl-N-aryloxyoxalyl-N-4-ethylbenzoyl Hydrazines (IIIa-l). To
a stirred solution of N-tert-butyl-N′-4-ethylbenzoyl-N-3,5-dimethyl-
benzoylhydrazide (A) (5.0 mmol) in anhydrous tetrahydrofuran (50 mL)
was added portionwise sodium hydride (0.24 g, 50% oil dispersion,
5.0 mmol) at room temperature under nitrogen. The mixture was stirred
at room temperature for 1 h and cooled to 0 °C, and then the substituted
aryloxyoxalyl chloride (II) (5.0 mmol) in anhydrous tetrahydrofuran
(8 mL) was added dropwise. After the addition was complete, the
reaction mixture was stirred for 5 h at room temperature. Then the
solid was filtered off, and the filtrate was concentrated under vaccum.
The residue was purified by column chromatography on a silica gel
using 6:1 petroleum ether (60-90 °C)/ethyl acetate as the eluent to
afford compounds IIIa-l as colorless crystallines.
General Synthetic Procedure for N′-tert-Butyl-N′-3,5-dimethyl-
benzoyl-N-aryloxyoxalyl-N-4-ethylbenzoyl Hydrazines (IVa-c). N′-
tert-Butyl-N′-3,5-dimethylbenzoyl-N-benzyloxycarbonylaryloxyoxalyl-
N-4-ethylbenzoyl hydrazines (IIId, IIIh, IIIl) (2.4 mmol) dissolved in
ethyl acetate (20 mL) were added to a catalytic amount (0.30 g) of 5%
palladium on carbon. The resulting mixture was stirred, and hydrogen
gas was introduced over 1.5 h at room temperature. Then the reaction
mixture was filtered to remove solids, and the organic filtrate was
Insecticidal Activity. Table 3 shows the insecticidal activity
of the parent compound (tebufenozide) and RH5849 (N-tert-
Scheme 2. General Synthetic Route for Compounds IV

Insecticidal Evaluation of N-Oxalyl Derivatives of Tebufenozide
J. Agric. Food Chem., Vol. 52, No. 22, 2004 6739
Table 1. Physical Properties and Elemental Analyses of N-Oxalyl Derivatives of Tebufenozide (IIIa
−l, IVa−c)
analysis calcd (found, %)
H
compd
R
mp (
°
C)
yield (%)
formula
C
N
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
IVa
IVb
IVc
BDPH
p-COOCH3
p-COOC4H9n
p-COOC3H7i
p-COOCH2C6H5
o-COOCH3
o-COOC4H9n
o-COOC3H7i
o-COOCH2C6H5
m-COOCH3
m- COOC4H9n
m- COOC3H7i
m-COOCH2C6H5
p-COOH
141
106
144
127
131
100
138
128
97
115
119
112
174
158
176
140
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
−
142
108
146
128
133
102
140
130
99
116
120
114
176
159
178
142
41.2
41.0
51.3
42.6
42.7
44.4
39.3
42.0
50.0
46.7
34.2
32.0
95.0
94.1
92.5
45
C32H34N2O7
C35H40N2O7
C34H38N2O7
C38H38N2O7
C32H34N2O7
C35H40N2O7
C34H38N2O7
C38H38N2O7
C32H34N2O7
C35H40N2O7
C34H38N2O7
C38H38N2O7
C31H32N2O7
C31H32N2O7
C31H32N2O7
C30H32N2O5
68.80 (69.00)
69.98 (69.77)
69.61 (69.64)
71.91 (71.90)
68.80 (68.80)
69.98 (70.10)
69.61 (69.64)
71.91 (71.79)
68.80 (68.81)
69.98 (70.15)
69.61 (69.56)
71.91 (71.80)
68.37 (68.40)
68.37 (68.21)
68.37 (68.18)
71.98 (71.87)
6.13 (6.09)
6.71 (6.90)
6.53 (6.59)
6.03 (6.05)
6.13 (6.10)
6.71 (6.90)
6.53 (6.47)
6.03 (6.00)
6.13 (6.09)
6.71 (6.93)
6.53 (6.64)
6.03 (6.06)
5.92 (5.84)
5.92 (5.86)
5.92 (5.87)
6.44 (6.48)
5.01 (5.17)
4.66 (4.63)
4.77 (4.65)
4.41 (4.53)
5.01 (5.23)
4.66 (4.65)
4.77 (4.89)
4.41 (4.48)
5.01 (5.06)
4.66 (4.84)
4.77 (4.85)
4.41 (4.33)
5.14 (5.34)
5.14 (5.19)
5.14 (5.20)
5.60 (5.71)
o-COOH
m-COOH
H
Table 2. 1H NMR Data of N-Oxalyl Derivatives of Tebufenozide
compd
1H NMR (CD3Cl),
7.5 Hz, 3H, Ph-CH2CH3); 1.68 (s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2); 2.63 (q, 3JHH
Ph-CH2CH3); 3.89 (s, 3H, OCH3); 6.44 7.90 (m, 11H, Ph)
0.97 (t, 3JHH 7.5 Hz, 3H, O(CH2)3CH3); 1.19 (t, 3JHH
7.5 Hz, 3H, Ph-CH2CH3); 1.39
(s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2); 2.63 (q, 3JHH 7.5 Hz, 2H, Ph-CH2CH3); 4.30 (t, 3JHH
6.44 7.90 (m, 11H, Ph)
1.20 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.35 (d, 3JHH
2.64 (q, 3JHH
7.5 Hz, 2H, Ph-CH2CH3); 5.16 5.26 (m, 1H, O
1.18 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.68 (s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2); 2.62 (q,3JHH
Ph-CH2CH3); 5.33 (s, 2H, O CH2); 6.44 7.93 (m, 16H, Ph)
1.26 (t, 3JHH 7.8 Hz, 3H, Ph-CH2CH3); 1.70 (s, 9H, C(CH3)3); 2.15 (s, 6H, Ph-(CH3)2); 2.69 (q, 3JHH
Ph-CH2CH3); 3.88 (s, 3 H, OCH3); 5.84 7.93 (m, 11H, Ph)
0.97 (t, 3JHH 7.5 Hz, 3H, O(CH2)3CH3); 1.25 (t, 3JHH
7.8 Hz, 3H, Ph-CH2CH3); 1.35
(s, 9H, C(CH3)3); 2.14 (s, 6H, Ph-(CH3)2); 2.68 (q, 3JHH
7.8 Hz, 2H, Ph-CH2CH3); 4.25
5.84 7.93 (m, 11H, Ph)
1.25 (t, 3JHH
7.5 Hz, 3H, Ph-CH2CH3); 1.34 (dd, 6H, J
2.67 (q, 3JHH
7.5 Hz, 2H, Ph-CH2CH3); 5.16 5.28 (m, 1H, O
1.25 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.67 (s, 9H, C(CH3)3); 2.15 (s, 6H, Ph-(CH3)2); 2.68 (q, 3JHH
Ph-CH2CH3); 5.34 (s, 2H, O CH2); 5.81 7.96 (m, 16H, Ph)
1.17 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.69 (s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2); 2.64 (q,3JHH
Ph-CH2CH3); 3.90 (s, 3H, OCH3); 6.58 7.86 (m, 11H, Ph)
0.90 (t, 3JHH 6.9 Hz, 3H, O(CH2)3CH3); 1.07 (t, 3JHH
7.5 Hz, 3H, Ph-CH2CH3); 1.32
(s, 9H, C(CH3)3); 2.09 (s, 6H, Ph-(CH3)2); 2.55 (q, 3JHH 7.5 Hz, 2H, Ph-CH2CH3); 4.22 (t, 3JHH
6.40 7.77 (m, 11H, Ph)
1.08 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.27 (d, 3JHH
2.55 (q, 3JHH
7.5 Hz, 2H, Ph-CH2CH3); 5.10 5.18 (m, 1H, O
1.12 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.69 (s, 9H, C(CH3)3); 2.16 (s, 6H, Ph-(CH3)2); 2.57 (q, 3JHH
Ph-CH2CH3); 5.34 (s, 2H, O CH2); 6.53 7.90 (m, 16H, Ph)
1.19 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.70 (s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2); 2.64 (q,3JHH
Ph-CH2CH3); 6.49 7.97 (m, 11H, Ph)
1.27 (t, 3JHH 7.8 Hz, 3H, Ph-CH2CH3); 1.69 (s, 9H, C(CH3)3); 2.14(s, 6H, Ph-(CH3)2); 2.69 (q, 3JHH
Ph-CH2CH3); 5.96 8.04 (m, 11H, Ph)
1.10 (t, 3JHH 7.5 Hz, 3H, Ph-CH2CH3); 1.61 (s, 9H, C(CH3)3); 2.09 (s, 6H, Ph-(CH3)2); 2.57 (q,3JHH
Ph-CH2CH3); 6.60 7.85 (m, 11H, Ph)
1.20 (t, 3JHH 7.5 Hz, 3H, Me), 1.70 (s, 9H, But), 2.17 (s, 6H, Me-Ph), 2.63 (q, 3JHH
δ
IIIa
1.19 (t, 3JHH
)
) 7.5 Hz, 2H,
−
IIIb
)
)
−
1.51 (m, 4H, O(CH2C2H4CH3); 1.69
)
)
6.6 Hz, 2H, O CH2);
−
−
IIIc
IIId
IIIe
IIIf
)
)
6.0 Hz, 6H, CH(CH3)2); 1.69 (s, 9H, C(CH3)3); 2.17 (s, 6H, Ph-(CH3)2);
CH); 6.44 7.90 (m, 11H, Ph)
)
−
−
−
)
)
7.5 Hz, 2H,
−
−
)
) 7.8 Hz, 2H,
−
)
)
−
1.47 (m, 4H, OCH2C2H4CH3); 1.70
)
−
4.34 (m, 2H, O CH2);
−
−
IIIg
IIIh
IIIi
)
)
6.0 Hz, CH(CH3)2); 1.70 (s, 9H, C(CH3)3); 2.14 (s, 6H, Ph-(CH3)2);
CH); 5.75 7.92 (m, 11H, Ph)
)
−
−
−
)
)
7.5 Hz, 2H,
−
−
)
) 7.5 Hz, 2H,
−
IIIj
)
)
−
1.44 (m, 4H, OCH2C2H4CH3); 1.61
)
)
6.0 Hz, 2H, O CH2);
−
−
IIIk
)
)
6.0 Hz, 6H, CH(CH3)2); 1.61 (s, 9H, C(CH3)3); 2.09 (s, 6H, Ph-(CH3)2);
CH); 6.36 7.76 (m, 11H, Ph)
)
−
−
−
IIIl
)
)
7.5 Hz, 2H,
7.5 Hz, 2H,
7.8 Hz, 2H,
7.5 Hz, 2H,
−
−
IVa
IVb
IVc
BDPH
)
)
−
)
)
)
−
)
−
)
) 7.5 Hz, 2H, CH2), 6.37−7.02 (m, 12H, Ph)
butyl-N,N′-dibenzoylhydrazine) and synthesized derivatives
against Oriental armyworm [Mythimna () Pseudaletia) separata
(Walker)]. The results indicate that some of these title com-
pounds exhibit higher larvicidal activities than RH5849 (N-tert-

6740 J. Agric. Food Chem., Vol. 52, No. 22, 2004
Mao et al.
LC50 (mg/L)
Table 3. Larvicidal Activities of N-Oxalyl Derivatives of Tebufenozide and Parent Compound, Tebufenozide
larvicidal activity (%) at
-1
-1
-1
-
1
-1
-
1
-1
compd
IIIa
500 mg kg
100 mg kg
50 mg kg
30 mg kg
25 mg kg
10 mg kg
5 mg kg
100
100
100
100
100
100
100
100
100
75
85
100
90
70
60
55
0
20
10
0
9.79
13.89
16.33
18.11
20.89
30.76
41.59
27.80
17.74
15.85
18.16
18.75
4.82
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
100
100
100
100
100
100
95
40
30
0
0
45
85
IIIh
10
0
15
15
0
IIIi
IIIj
IIIk
IIIl
100
100
100
100
100
75
95
90
42.5
100
IVa
IVb
100
100
95
45
0
336.51
5.16
1.59
IVc
100
95
100
73.3
100
55
70
tebufenozide
RH5849
100
100
24.38
butyl-N,N′-dibenzoylhydrazine), but they are not good compared
to the parent compound (tebufenozide). For example, the most
active compound, IVa, requires 3 times the concentration for
the LC50 as does tebufenozide. Toxicity assays indicated that
the title compounds, like the parent compound, can induce a
premature, abnormal, and lethal larval molt. Symptoms of
toxicity included discoloration, weight loss, cessation of feeding,
and developmentally premature, lethal molting at higher rates.
It is interesting to note that the larvicidal activities of the
title compounds appeared to be strongly associated with the
substituent R and its position on the benzene. The derivatives
with substituent R at the meta or para position are obviously
superior to those with R at the ortho position. The derivatives
containing carboxylic acid (IVa and IVc) are much better than
those containing carboxylate ester, and those derivatives con-
taining carboxylic acid on the meta or para (IVa and IVc)
position are comparable to the patent compound tebufenozide.
Compound IVb displayed reduced larvicidal activity, maybe
because the H atom of carboxylic acid at the ortho of the
benzene ring can provide an intramolecular hydrogen bond with
the carbonyl of the oxalyl group, which alters the properties of
the compound.
in water and limited solubility in common organic solvents, so
application of such diacylhydrazines in water and as emulsifiable
concentrates is not ordinarily feasible (9). Compared to the
parent compound (tebufenozide), the title compounds displayed
better solubility in organic solvents such as methylene dichlo-
ride, chloroform, toluene, and xylene, which should make them
easier to apply under field conditions.
It was reported that for an insecticide to be phloem mobile,
a -COOH functional group would be necessary (15); therefore,
substitution of a carboxylate or carboxylic acid group to
tebufenozide may help phloem movement of the compound.
However, we found that the title compounds have no systemic
activity.
Conclusions. In summary, a series of novel N′-tert-butyl-
N′-3,5-dimethylbenzoyl-N-aryloxyoxalyl-N-4-ethylbenzoyl hy-
drazines contaning carboxylic acid or carboxylate substituent
on the aryl were synthesized. The results of bioassays showed
that some of these title compounds exhibit higher larvicidal
activities than RH5849 (N-tert-butyl-N,N′-dibenzoylhydrazine),
but they are not good compared to the parent compound
(tebufenozide). The carboxylic acid substituent on the aryl was
essential for high larvicidal activity. Compared to the parent
compound, these derivatives displayed different physical proper-
ties, which may lead to compounds with better biological activity
and characteristics.
To explore further the effect of the carboxylic acid substituent
on the aryl upon larvicidal activity, N′-tert-butyl-N′-3,5-di-
methylbenzoyl-N-phenyloxyoxalyl-N-4-ethylbenzoyl hydrazine
(BDPH) was synthesized using the same procedure as shown
in Scheme 1.
LITERATURE CITED
(1) Wing, K. D. RH5849, a nonsteroidal ecdysone agonist: effects
on a Drosophila cell line. Science (Washington, D.C.) 1988, 241,
467.
(2) Wing, K. D.; Slawecki, R. A.; Carlson G. R. RH5849, a
nonsteroidal ecdysone agonist effects on Lepidoptera. Science
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Received for review July 14, 2004. Revised manuscript received August
26, 2004. Accepted August 28, 2004. This work was supported by the
National Key Project for Basic Research (2003CB114400), the National
Natural Science Foundation of China (20202005), the Research Fund
for the Doctoral Program of Higher Education (20010055006), and the
Foundation for the Author of National Excellent Doctoral Dissertation
of the People’s Republic of China (200255).
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