Syntheses and insecticidal activities of novel 2-fluorophenyl-5-aryl/cyclopropyl-1,3,4-oxadiazoles

Article abstract of DOI:10.1016/S0022-1139(00)00323-7

Two 2-fluorophenyl-5-substitued cyclopropyl-1,3,4-oxadiazoles (IIIa-b) with cis/trans isomers were synthesized from the corresponding hydrazide (Ia) and aroyl chlorides by two-step reactions. Six asymmetrical 2-(2,4-dichloro-5-fluorophenyl)-5-aryl-1,3,4-oxadiazoles (IIIc-h) were obtained by one step reaction of 2,4-dichloro-5-fluorobenzoic acid hydrazide (Ic) with the corresponding aromatic carboxylic acid in the presence of phosphorus oxychloride under reflux. However, the similar reaction of 4-fluorophenoxyacetic acid hydrazide (Ib) with 2,4-dichloro-5-fluorobenzoic acid failed to yield the desired asymmetrical 2-(2,4-dichloro-5-fluorophenyl)-5-(fluorophenoxymethyl)-1,3,4-oxadiazole, and the resulting product was characterized as symmetrical 2,5-bis(2,4-dichloro-5-fluorophenyl)-1,3,4-oxadiazole (DCFPO). A possible reaction mechanism is suggested. Insecticidal activities of these nine new compounds against armyworms (Pseudaletia separata Walker) were determined.

Full text of DOI:10.1016/S0022-1139(00)00323-7

Journal of Fluorine Chemistry 106 (2000) 173±179
Syntheses and insecticidal activities of novel
-¯uorophenyl-5-aryl/cyclopropyl-1,3,4-oxadiazoles
2
a
Wei Shi , Xuhong Qian , Gonghua Song , Rong Zhang , Rongpo Li
b,*
a
a
a
a
Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology,
PO Box 544, 130 Meilong Road, Shanghai 200237, China
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China
b
Received 3 May 2000; accepted 14 July 2000
Abstract
Two 2-¯uorophenyl-5-substitued cyclopropyl-1,3,4-oxadiazoles (IIIa±b) with cis/trans isomers were synthesized from the corresponding
hydrazide (Ia) and aroyl chlorides by two-step reactions. Six asymmetrical 2-(2,4-dichloro-5-¯uorophenyl)-5-aryl-1,3,4-oxadiazoles (IIIc±
h) were obtained by one step reaction of 2,4-dichloro-5-¯uorobenzoic acid hydrazide (Ic) with the corresponding aromatic carboxylic acid
in the presence of phosphorus oxychloride under re¯ux. However, the similar reaction of 4-¯uorophenoxyacetic acid hydrazide (Ib) with
2
,4-dichloro-5-¯uorobenzoic acid failed to yield the desired asymmetrical 2-(2,4-dichloro-5-¯uorophenyl)-5-(¯uorophenoxymethyl)-1,3,4-
oxadiazole, and the resulting product was characterized as symmetrical 2,5-bis(2,4-dichloro-5-¯uorophenyl)-1,3,4-oxadiazole (DCFPO). A
possible reaction mechanism is suggested. Insecticidal activities of these nine new compounds against armyworms (Pseudaletia separata
Walker) were determined. # 2000 Elsevier Science S.A. All rights reserved.
Keywords: Fluoroaryl; 1,3,4-Oxadiazoles; Cis/trans isomers; One step reaction; Insecticidal activity; Armyworm
1
. Introduction
dentally synthesized (Scheme 2). It was found that
DCFPO has better insecticidal activities toward army-
worms and better solubility in a majority of organic polar
solvents than DCPO [3]. In addition, organic ¯uorides
have good and extensive biological activities allowing
their possible application in pharmaceuticals and pesti-
cides [4]. These facts prompted us to synthesize six
other asymmetrical 2-(2,4-dichloro-5-¯uorophenyl)-5-
aryl-1,3,4-oxadiazoles (IIIc±h, Scheme 3). These new
compounds might be expected to have good insecticidal
activities and improved solubility.
Symmetrical 2,5-bis(2,4-dichlorophenyl)-1,3,4-oxadia-
zole (DCPO) and analogs were found to be effective insec-
ticides toward house¯ies, face¯ies and horn¯ies [1].
However, DCPO's limited solubility in polar solvents made
it commercially unattractive, therefore, it could be useful to
®
nd new 2,5-disubstituted-1,3,4-oxadiazoles which might
2
. Results and discussion
show similar or enhanced biological activities and possess
favorable solubility [2]. Since pyrethroids are ef®cient
insecticides, we introduced one of their typical groups,
2
.1. Synthesis
2
,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropyl, to synthe-
Starting from three different compounds 1±3, hydrazides
Ia±c were prepared (Scheme 4).
size two 2-¯uorophenyl-5-[2,2-dimethyl-3-(2,2-dichlorovi-
nyl)-cyclopropyl]-1,3,4-oxadiazoles (IIIa±b, Scheme 1). In
an experiment, a novel compound, 2,5-bis(2,4-dichloro-
Asymmetrical 2,5-disubstituted-1,3,4-oxadiazoles are
0
usually synthesized from N,N -diacylhydrazines [2]. By this
method, compounds IIIa±b were prepared from hydrazide
5
-¯uorophenyl)-1,3,4-oxadiazole (DCFPO), was acci-
0
1
*
Ia via N,N -diacylhydrazines IIa±b (Scheme 1). The H
NMR spectra of compound 1 and the above compounds
Corresponding author.
E-mail address: xhqian@ecust.edu.cn (X. Qian).
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 3 2 3 - 7

1
74
W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
Scheme 1. Conventional route for synthesis of asymmetrical 2,5-disubstituted-1,3,4-oxadiazoles (IIIa±b).
Scheme 2. Route for synthesis of DCFPO.
Scheme 3. Simple route for synthesis of asymmetrical 2,5-disubstituted-1,3,4-oxadiazoles (IIIc±h).
(
except IIIb) showed two sets of signals at d 1.00±7.00 ppm
vinyl hydrogen in cis and trans con®gurations followed the
rule dtrans < dcis [6]. The doublet at d 6.20±6.40 ppm
(J ˆ 8:50� 9:00 Hz) is attributed to the cis isomer and the
doublet at d 5.50±5.80 ppm (J ˆ 8:00� 8:30 Hz) is attrib-
uted to the trans isomer. Because separation of cis and trans
isomers is very dif®cult, they were not separated. However,
according to the integration ratio of the dichlorovinyl CH in
corresponding to cis and trans isomers on the three-mem-
bered cyclopropyl ring [5,6] (see data given in Section 3).
Two doublets at d 6.20±6.40 and 5.50±5.80 ppm for one
proton are attributed to the dichlorovinyl CH. Examination
of H NMR data found in the literature for cyclopropyl
compounds revealed that the chemical shifts of the dichloro-
1
1
the H NMR spectra of compounds 1, Ia, IIa±b and IIIa±b,
the cis/trans contents of these compounds can be estimated
(
cis: 1, Ia, IIa±b about 40%; IIIa about 19%; IIIb zero). The
closer the ratio of cis:trans is to 1:1, the longer the melting
range is (see data given in Section 3). The formation of the
oxadiazole ring makes steric hindrance increase more
greatly in the cis con®guration than in the trans con®gura-
tion, so the content of cis isomer decreases in compound IIIa
and becomes zero in compound IIIb.
Later, we found a simple method by which oxadiazoles
could be directly synthesized from carboxylic acids and
0
hydrazides in one step. Although N,N -diacylhydrazines
need not be synthesized, it is likely that they are ®rst
produced by an intermolecular nucleophilic displacement
reaction (Scheme 5) and then transformed into oxadiazoles.
0
This view is supported by the fact that only N,N -diacylhy-
drazines were obtained by this method in some experiments.
For example, the similar reaction of 4-¯uorophenoxyacetic
acid hydrazide with trimethylacetic acid gave only
Scheme 4. Routes for synthesis of three different hydrazides (Ia±c).

W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
175
Scheme 5. A possible mechanism for formation of diacylhydrazines by one step method.
0
N-trimethylacetyl-N -(4-¯uorophenoxyacetyl)hydrazine.
Because the simple method needs more time and the reac-
tion condition of cyclization is harsh, it is necessary that the
hydrazides should be stable. We found that this method
might be unsuitable for aliphatic hydrazides (e.g. compound
Ia) because a large amount of tar was produced and the yield
was rather low.
2.2. Insecticidal activities
The insecticidal activities against armyworms for com-
pounds IIIa±h, DCFPO and the check sample DCPO are
listed in Table 1.
By comparing the insecticidal activities of compounds
IIIa, IIIb, IIId, IIIf, IIIh, DCFPO and DCPO, it was found
that their activities against armyworms increased in the
following order: IIIh < IIIa < IIIb << IIId < DCPO <
IIIf < DCFPO. So it could be concluded that with the
increase of electron-withdrawing power, insecticidal activ-
ity of oxadiazoles against armyworms increases. However,
when a strong electron-withdrawing group ±NO2 was
further introduced into DCFPO, the activity decreased
greatly. In view of this, it might be implied that there is
It is interesting that symmetrical 2,5-bis(2,4-dichloro-5-
uorophenyl)-1,3,4-oxadiazole (DCFPO) was synthesized
from 4-¯uorophenoxyacetic acid hydrazide and 2,4-
dichloro-5-¯uorobenzoic acid because the expected product
was asymmetrical 2-(2,4-dichloro-5-¯uorophenyl)-5-(4-
¯
¯
uorophenoxymethyl)-1,3,4-oxadiazole (DCFPO and its
analogs are being applied for a patent) [3]. Because 2,4-
dichloro-5-¯uorobenzoic acid was in excess, we believe
that an exchange reaction occurs (Scheme 6) between the
carboxylic acid and the diacylhydrazine which was formed
via the mechanism shown in Scheme 5. Furthermore,
we think that it might be more dif®cult to transform
an optimum electron-withdrawing power or that ±NO is too
2
big. In addition, the presence of a pyridyl ring is unfavorable
for the activity against armyworms and the presence of a 2,2-
dimethyl-3-(2,2-dichlorovinyl)-cyclopropyl group does not
obviously increase insecticidal activity.
0
N-(2,4-dichloro-5-¯uorobenzoyl)-N -(4-¯uorophenoxyace-
tyl)hydrazine into 2-(2,4-dichloro-5-¯uorophenyl)-5-(4-
¯
N,N -bis(2,4-dichloro-5-¯uorobenzoyl)hydrazine
uorophenoxymethyl)-1,3,4-oxadiazole than to transform
0
into
3. Experimental
0
DCFPO. With the continuous consumption of N,N -
bis(2,4-dichloro-5-¯uorobenzoyl)hydrazine, the above ex-
change reaction is favorable for the formation of
Melting points were taken on a digital melting point
apparatus made in Shanghai and are uncorrected. 1H
NMR spectra were recorded with Bruker WP-500SY
0
N,N -bis(2,4-dichloro-5-¯uorobenzoyl)hydrazine.
Scheme 6. A possible reaction mechanism for formation of DCFPO.

1
76
W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
Table 1
3.1.2. Preparation of 4-fluorophenoxyacetic acid
hydrazide (Ib)
Percent mortality (%) and LC50 (mg/l) of oxadiazoles IIIa±h, DCFPO and
DCPO against armyworms
4
-Fluorophenol (2) (16.8 g, 150 mmol) was dissolved in
Compounds
Conc.
mg/l)
Percent
LC50 (mg/l)
anhydrous acetone (45 ml). To the solution were added ethyl
chloroacetate (22.5 g, 180 mmol) and anhydrous potassium
carbonate (41.25 g, 300 mmol). The reaction mixture
obtained was re¯uxed for 20 h, while stirring. When hot,
the reaction mixture was ®ltered under aspirator pressure.
The solvent was removed from the ®ltrate under reduced
pressure to give a reddish brown liquid. After the liquid had
stood for a few hours, the resulting precipitate was ®ltered
off to give the crude 4-¯uorophenoxyacetic acid ethyl ester.
A mixture of the above ester, hydrazine monohydrate
(
mortality (%)
IIIa
IIIb
IIIc
IIId
500
500
500
125
31
43
0
>500
>500
±
100
57
20
10
0
51.18
5
2
1
0
5
2.5
IIIe
IIIf
500
25
±
100
93
73
13
0
5.22
1
2.5
(
1
63.70 g, 1.25 mol) and ethanol (75 ml) was re¯uxed for
4 h. After cooling to room temperature, the resulting pre-
6
3
.25
.125
IIIg
IIIh
500
500
5
±
cipitate was ®ltered, washed and dried to produce white
needles, yield 31%. The needles were recrystallized from
ethanol to produce white needle crystals, mp 132.1±
0
±
1.77
100
57
7
DCFPO
DCPO
2.5
1
C H FN O (184): C, 52.17; H, 4.92; N, 15.21%. Found:
32.98C. Rf ˆ 0:18 (ethyl acetate). Analysis: Calc. for
1
.25
20
1
93
27
17
10.13
8
9
2 2
0
C, 52.22; H, 4.93; N, 15.27%.
5
3.1.3. Preparation of 2,4-dichloro-5-fluorobenzoic acid
hydrazide (Ic)
A mixture of 2,4-dichloro-5-¯uorobenzoic acid (3)
8.36 g, 40 mmol) and thionyl chloride (16 ml) was re¯uxed
(
(
500 MHz) spectrometer with CDCl as the solvent and
3
for 2 h. The excess thionyl chloride was removed by dis-
tillation under normal pressure. Benzene (5 ml) was added
to the distillation pot and then distilled under reduced
pressure to give crude 2,4-dichloro-5-¯uorobenzoyl chlor-
ide. The crude acyl chloride was added dropwise to anhy-
drous ethanol (15 ml) over 45 min, while stirring. The
reaction mixture was stirred for 12 h at room temperature.
The excess ethanol was evaporated under reduced pressure
to give the light yellow liquid, 2,4-dichloro-5-¯uorobenzoic
acid ethyl ester. A mixture of the above ester, hydrazine
monohydrate (20.38 g, 400 mmol) and ethanol (20 ml) was
re¯uxed for 10 h. After cooling to room temperature, the
resulting precipitate was ®ltered, washed and dried to pro-
duce white needles, yield 72%. The solid was recrystallized
from ethanol to give white needle crystals, mp 171.2±
TMS as the internal standard. Infrared spectra were mea-
sured on KBr disks using a Nicolet FT-IR-20SX instrument.
Mass spectra were obtained on a Hitachi M80 instrument.
Combustion analyses for elemental composition were made
with an Italian MOD.1106 analyzer. All reactions were
monitored by TLC.
3
3
.1. Preparation of hydrazides
.1.1. Preparation of 2,2-dimethyl-3-(2,2-dichlorovinyl)-
cyclopropanecarboxylic acid hydrazide (Ia)
A mixture of 2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclo-
propanecarboxylic acid methyl ester (1) (2.23 g, 10 mmol)
and hydrazine monohydrate (5 g, 100 mmol) was boiled
under re¯ux for 12 h. After cooling to room temperature,
the precipitate was collected, washed and dried to give a
yellowish solid, yield 90%. The solid was recrystallized
from ethanol to give yellowish grainy crystals, mp 54.4±
171.98C. R ˆ 0:18 (ethyl acetate). IR (KBr): 3300, 3050,
f
�
1
1650, 1610, 1560, 1520, 1460, 1380, 1000, 950, 880 cm
1
.
H NMR (CDCl ): d 8.93 (s 1H, NH), 7.65 (d, J
H;F
ˆ
3
8:98 Hz, 1H, ArH), 7.62 (d, JH;F ˆ 6:51 Hz, 1H, ArH).
Analysis: Calc. for C H Cl FN O (223): C, 37.67; H,
7
5
2
2
7
IR (KBr): 3300, 3050, 2950, 1645, 1615, 1540, 1430, 1380,
0.18C (cis:trans ˆ 37:2:62.8). Rf ˆ 0:20 (ethyl acetate).
2.24; N, 12.56%. Found: C, 37.46; H, 2.06; N, 12.37%.
50, 810 cm . 1H NMR (CDCl ): d cis: 6.36 (d, J ˆ
�
1
3.2. General procedure for preparation of N-aroyl-N -[2,2-
dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarbonyl]-
hydrazine
0
8
8
1
5
5
3
:80 Hz, 1H, Cl CCH), 2.01 (dd, J ˆ 8:80 Hz, 1H, CH),
2
.58 (d, J ˆ 8:80 Hz, 1H, CH), 1.10±1.27 (6H, 2CH ); trans:
3
.62 (d, J ˆ 8:26 Hz, 1H, Cl CCH), 2.27 (dd, J ˆ 8:26 and
2
.27 Hz, 1H, CH), 1.41 (d, J ˆ 5:27 Hz, 1H, CH), 1.10±1.27
2,2-Dimethyl-3-(2,2-dichlorovinyl)-cyclopropanecarboxy-
lic acid hydrazide (Ia) (1.56 g, 7 mmol), NaHCO (0.588 g,
(
6H, 2CH ). Analysis: Calc. for C H Cl N O (223): C,
3
8
12
2
2
3
4
1
3.05; H, 5.38; N, 12.56%. Found: C, 42.87; H, 5.30; N,
2.44%.
7 mmol), THF (8 ml) and H O (4 ml) were mixed. To the
2
mixture was added dropwise a solution of the aroyl chloride

W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
177
containing ¯uorine (7 mmol) in THF (6 ml) over 30 min,
while stirring. The reaction mixture was stirred for 3 h at
room temperature. The solvent was removed in vacuo and a
solid obtained was washed and dried to give the crude
product.
After cooling to room temperature, it was poured slowly into
an ice and water mixture. The resulting precipitate was
®ltered, washed, dried and recrystallized twice from ethanol
to produce white needle crystals, yield 67%, mp 150.0±
154.98C (cis:trans ˆ 18:7:81.3). Rf ˆ 0:72 (ethyl acetate:-
petroleum ether ˆ 1:2, v/v). IR (KBr): 3100, 2900, 1600,
0
� 1
1
3
.2.1. N-(3-fluorobenzoyl)-N -[2,2-dimethyl-3-(2,2-
dichlorovinyl)-cyclopropanecarbonyl]hydrazine (Ia)
1570, 1560, 1490, 1240, 1190, 890, 870, 830 cm . H
NMR (CDCl ): d cis: 7.83 (m, 1H, ArH), 7.73 (m, 1H,
3
This compound was obtained as a light orange solid from
ArH), 7.49 (m, 1H, ArH), 7.23 (m, 1H, ArH), 6.28 (d, J ˆ
3
-¯uorobenzoyl chloride, yield 92%. The solid was recrys-
tallized from ethanol to give yellowish powdery crystals, mp
5.3±101.98C (cis:trans ˆ 38:9:61.1). Rf ˆ 0:36 (ethyl
8:76 Hz, 1H, Cl CCH), 2.38 (d, J ˆ 8:76 Hz, 1H, CH), 2.27
2
(dd, J ˆ 8:76 Hz, 1H, CH), 1.29±1.38 (6H, 2CH ); trans:
3
8
7.83 (m, 1H, ArH), 7.73 (m, 1H, ArH), 7.49 (m, 1H, ArH),
7.23 (m, 1H, ArH), 5.74 (d, J ˆ 8:08 Hz, 1H, Cl CCH), 2.48
acetate:petroleum ether ˆ 1:2, v/v). IR (KBr): 3250,
2
3
8
1
050, 2950, 1690, 1650, 1590, 1530, 1490, 1260, 890,
40, 750 cm . H NMR (CDCl ): d cis: 9.86±10.12 (m,
H, NH), 9.50 (s, 1H,NH), 7.95 (m, 1H, ArH), 7.54 (m, 1H,
(dd, J ˆ 8:08 and 5.57 Hz, 1H, CH), 2.13 (d, J ˆ 5:57 Hz,
�
1
1
1H, CH), 1.29±1.38 (6H, 2CH ). Analysis: Calc. for
3
3
C H Cl FN O (327): C, 55.05; H, 3.98; N, 8.56%. Found:
2
15
13
2
ArH), 7.38 (m, 1H, ArH), 7.21 (m, 1H, ArH), 6.30 (d, J ˆ
C, 54.85; H, 3.96; N, 8.66%.
8
:66 Hz, 1H, Cl CCH), 2.04 (dd, J ˆ 8:66 Hz, 1H, CH), 1.81
2
(
d, J ˆ 8:66 Hz, 1H, CH), 1.15±1.27 (6H, 2CH ); trans:
3.3.2. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-
[2,2-dimethyl-3-(2,2-dichlorovinyl)-cyclopropyl]-1,3,4-
oxadiazole (IIIb)
3
9
ArH), 7.54 (m, 1H, ArH), 7.38 (m, 1H, ArH), 7.21 (m, 1H,
.86±10.12 (m, 1H, NH), 9.50 (s, 1H, NH), 7.95 (m, 1H,
ArH), 5.56 (d, J ˆ 8:23 Hz, 1H, Cl CCH), 2.30 (dd, J ˆ
This compound was prepared as white needle crystals
from (IIb) as described in Section 3.3.1, yield 60%, mp
2
8
1
:23 and 5.28 Hz, 1H, CH), 1.63 (d, J ˆ 5:28 Hz, 1H, CH),
.15±1.27 (6H, 2CH ). Analysis: Calc. for C H Cl FN O
3
139.1±140.28C. R ˆ 0:72 (ethyl acetate:petroleum ether ˆ
15 15
2
2
2
f
(
4
345): C, 52.17; H, 4.35; N, 8.12%. Found: C, 52.07; H,
.37; N, 7.99%.
1:2, v/v). IR (KBr): 3050, 2950, 1570, 1500, 1480, 1360,
1250, 1090, 890, 830, 730 cm . H NMR (CDCl ): d trans:
�
1
1
3
7
.84 (d, JH;F ˆ 8:99 Hz, 1H, ArH), 7.63 (d, JH;F ˆ 6:53 Hz,
0
3
3
.2.2. N-(2,4-dichloro-5-fluorobenzoyl)-N -[2,2-dimethyl-
-(2,2-dichlorovinyl)-cyclopropanecarbonyl] hydrazine
1H, ArH), 5.76 (d, J ˆ 8:11 Hz, 1H, Cl CCH), 2.49 (dd, J ˆ
2
8:11 and 5.56 Hz, 1H, CH), 2.19 (d, J ˆ 5:56 Hz, 1H, CH),
(
IIb)
This compound was obtained as a gray solid from 2,4-
dichloro-5-¯uorobenzoyl chloride, yield 88%. The solid was
recrystallized from ethanol to give white powdery crystals,
1.33±1.35 (6H, 2CH ). Analysis: Calc. for C H Cl FN O
2
3
15 11
4
(396): C, 45.45; H, 2.78; N, 7.07%. Found: C, 45.21; H,
2.70; N, 7.16%.
mp 127.4±141.98C (cis:trans ˆ 39:0:61.0). R ˆ 0:36 (ethyl
3.3.3. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-(2-
chloro-3-pyridyl)-1,3,4-oxadiazole (IIIc)
f
acetate:petroleum ether ˆ 1:2, v/v). IR (KBr): 3250, 3050,
2
7
9
950, 1700, 1650, 1520, 1480, 1420, 1390, 1240, 890, 850,
30 cm . H NMR (CDCl ): d cis: 9.75±9.94 (m, 1H, NH),
.54 (s, 1H, NH), 7.61 (d, JH;F ˆ 8:84 Hz, 1H, ArH), 7.53 (d,
A mixture of 2,4-dichloro-5-¯uorobenzoic acid hydrazide
(Ic) (1.12 g, 5 mmol), 2-chloro-3-pyridinecarboxylic acid
(0.70 g, 5 mmol) and POCl (10 ml) was re¯uxed at 105±
�
1
1
3
3
JH;F ˆ 6:31 Hz, 1H, ArH), 6.35 (d, J ˆ 8:99 Hz, 1H,
1108C for 6 h. After cooling to room temperature, it was
poured slowly into an ice and water mixture (100 ml). The
resulting precipitate was ®ltered, washed, dried and recrys-
tallized from ethanol to produce off-white powdery crystals,
Cl CCH), 2.10 (dd, J ˆ 8:99 Hz, 1H, CH), 1.84 (d, J ˆ
2
8
:99 Hz, 1H, CH), 1.20±1.31 (6H, 2CH ); trans: 9.75±9.94
3
(
m, 1H, NH), 9.54 (s, 1H,NH), 7.57 (d, JH;F ˆ 8:84 Hz, 1H,
ArH), 7.51 (d, JH;F ˆ 6:31 Hz, 1H, ArH), 5.63 (d, J ˆ
yield 57%, mp 154.1±154.98C. R ˆ 0:70 (ethyl acetate:pe-
f
1
8
1
2
4
6
:11 Hz, 1H, Cl CCH), 2.33 (dd, J ˆ 8:11 and 4.70 Hz,
troleum ether ˆ 1:2, v/v). H NMR (CDCl ): d 8.65 (dd,
2
3
H, CH), 1.63 (d, J ˆ 4:70 Hz, 1H, CH), 1.20±1.31 (6H,
J ˆ 4:76 and 1.96 Hz, 1H), 8.52 (dd, J ˆ 7:78 and 1.96 Hz,
1H), 8.00 (d, JH;F ˆ 8:89 Hz, 1H), 7.71 (d, JH;F ˆ 6:50 Hz,
1H), 7.50 (dd, J ˆ 4:76 and 7.78 Hz, 1H). Analysis: Calc.
for C H Cl FN O (344.5): C, 45.28; H, 1.45; N, 12.19%.
CH ). Analysis: Calc. for C H Cl FN O (414): C,
2 2
3
15 13
4
3.48; H, 3.14; N, 6.76%. Found: C, 43.19; H, 3.21; N,
.55%.
13
5
3
3
Found: C, 45.62; H, 1.42; N, 12.59%.
3
.3. Preparation of 2,5-disubstituted-1,3,4-oxadiazoles
3.3.4. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-(3-
fluorophenyl)-1,3,4-oxadiazole (IIId)
This compound was prepared as light brown grainy
crystals from 3-¯uorobenzoic acid as described in 3.3.3,
3
3
.3.1. Preparation of 2-(3-fluorophenyl)-5-[2,2-dimethyl-
-(2,2-dichlorovinyl)-cyclopropyl]-1,3,4-oxadiazole (IIIa)
0
A mixture of N-(3-¯uorobenzoyl)-N -[2,2-dimethyl-3-
2,2-dichlorovinyl)-cyclopropanecarbonyl]hydrazine (IIa)
(
(
yield 55%, mp 135.8±137.08C. R ˆ 0:68 (ethyl acetate:
f
1
1.73 g, 5 mmol) and POCl (10 ml) was re¯uxed for 3 h.
3
petroleum ether ˆ 1:2, v/v). H NMR (CDCl ): d 7.96 (m,
3

1
78
W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
2
1
H), 7.84 (m, 1H), 7.67 (d, JH;F ˆ 6:52 Hz, 1H), 7.55 (m,
H), 7.30 (m, 1H). Analysis: Calc. for C H Cl F N O
4:1, v/v) as eluent to give a white solid, yield 28%. The solid
was recrystallized from ethanol to give white powdery
crystals, mp 167.4±168.18C. Rf ˆ 0:64 (ethyl acetate:petro-
leum ether ˆ 1:2, v/v). IR (KBr): 2950, 2900,2850, 1610,
1
4
6
2 2 2
(
1
327): C, 51.38; H, 1.83; N, 8.56%. Found: C, 51.77; H,
.79; N, 8.99%.
1
7
500, 1460, 1260, 1100, 1080, 1010, 890, 860, 790,
�
1
1
30 cm . H NMR (CDCl ): d 8.10 (d, J ˆ 7:88 Hz, 2H,
3
3.3.5. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-(6-
chloro-3-pyridyl)-1,3,4-oxadiazole (IIIe)
This compound was prepared as off-white powdery crys-
tals from 6-chloro-3-pyridinecarboxylic acid as described in
ArH), 7.96 (d, J ˆ 8:91 Hz, 1H, ArH), 7.66 (d, J
ˆ
H;F
H;F
6
3
:53 Hz, 1H, ArH), 7.05 (d, J ˆ 7:88 Hz, 2H, ArH), 3.91 (s,
3
H, OCH ). MS (EI 70 eV), (m/e, %): 338 (21.501) [M]; 340
(
(
15.070) [M ‡ 2]; 342 (3.278) [M ‡ 4]; 247 (7.335); 191
3
.3.3, yield 52%, mp 188.9±190.28C. Rf ˆ 0:70 (ethyl
15.076); 163 (6.470); 135 (100); 119 (8.299); 107 (5.864);
1
acetate:petroleum ether ˆ 1:2, v/v). H NMR (CDCl ): d
3
9
C H Cl FN O (339): C, 53.10; H, 2.65; N, 8.26%. Found:
2
(16.394); 77 (19.426). Analysis: Calc. for
9
8
6
.14 (dd, J ˆ 2:42 and 0.63 Hz, 1H), 8.41 (dd, J ˆ 2:42 and
15
9
2
2 2
.36 Hz, 1H), 7.96 (d, J ˆ 8:86 Hz, 1H), 7.68 (d, J
H;F
ˆ
H;F
C, 52.96; H, 2.37; N, 8.32%.
:49 Hz, 1H), 7.56 (dd, J ˆ 8:36 and 0.63 Hz, 1H). Analy-
sis: Calc. for C H Cl FN O (344.5): C, 45.28; H, 1.45; N,
1
3
5
3
3
1
2.19%. Found: C, 45.29; H, 1.50; N, 12.47%.
3.3.9. Preparation of 2,5-bis(2,4-dichloro-5-flurophenyl)-
1
,3,4-oxadiazole (DCFPO)
The mixture of 4-¯uorophenoxyacetic acid hydrazide (Ib)
3
.3.6. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-
2,4-dichlorophenyl)-1,3,4-oxadiazole (IIIf)
(
2
1.84 g, 5 mmol), 2,4-dichloro-5-¯uorobenzoic acid (4.18 g,
0 mmol) and POCl (10 ml) was re¯uxed for 5 h. After
(
3
This compound was prepared as small yellowish needle
cooling, it was poured into broken ice. The resulting white
precipitate was ®ltered, washed with diluted sodium hydro-
xide water solution and then water, dried and recrystallized
twice from ethanol to give white ¯ake crystals, yield 58%,
crystals from 2,4-dichlorobenzoic acid as described in 3.3.3,
yield 61%, mp 183.4±184.48C. Rf ˆ 0:68 (ethyl acetate:pe-
troleum ether ˆ 1:2, v/v). IR (KBr): 3060, 3020,1590, 1565,
�
1
1
1
480, 1460, 1250, 1100, 1080, 880, 860, 730 cm . H
mp 176.1±176.28C. Rf ˆ 0:80 (CHCl ). IR (KBr): 3080,
3
NMR (CDCl ): d 8.09 (d, J ˆ 8:48 Hz, 1H), 7.97 (d,
3
� 1
1
2
920,1610, 1580, 1460, 1260, 1095, 890, 730, 670 cm . H
J
ˆ 8:92 Hz, 1H), 7.68 (d, J ˆ 6:51 Hz, 1H), 7.62
H;F
H;F
NMR (CDCl ): d 8.33 (d, J ˆ 9:61 Hz, 2H), 8.19 (d,
3
H;F
(
1
d, J ˆ 2:02 Hz, 1H), 7.45 (dd, J ˆ 8:48 and 2.02 Hz,
JH;F ˆ 6:57 Hz, 2H). MS (EI 70 eV), (m/e, %): 393 (18.991)
H). MS (EI 70 eV), (m/e, %): 376 (6.833) [M]; 378
[
(
1
4
7
M � 1]; 395 (21.946) [M ‡ 1]; 397 (4.566) [M ‡ 3]; 399
3.381), [M ‡ 5]; 305 (23.959); 191 (100); 163 (33.371);
(
[
(
(
6.778) [M ‡ 2]; 380 (5.367) [M ‡ 4]; 382 (2.319),
M ‡ 6]; 285 (18.673); 191 (63.399); 173 (100); 163
26.375); 145 (29.431); 109 (25.552); 75 (22.700); 74
23.836). Analysis: Calc. for C H Cl FN O (378): C,
43 (3.367). Analysis: Calc. for C H Cl FN O (378): C,
14 5 4 2
4.44; H, 1.32; N, 7.41%. Found: C, 44.72; H, 1.39; N,
.67%.
14
5
4
2
4
7
4.44; H, 1.32; N, 7.41%. Found: C, 44.72; H, 1.39; N,
.67%.
3
.4. The method for investigation of effect on armyworms
pseudaletia separata walker)
(
3
.3.7. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-
(
(
2,4-dichloro-3-nitro-5-fluorophenyl)-1,3,4-oxadiazole
IIIg)
This compound was prepared as a yellow solid from 2,4-
A test solution was made by dissolving the compound in a
small amount of DMF, then adding a few drops of surfactant,
and ®nally adding water to a proper volume. Concentration
is de®ned as mass (mg) of the compound per liter of solution.
A moderate amount of corn leaves treated by the above test
solution were placed on moistened ®lter paper in broad
bottles. Each bottle was infested with 10 s-instar larvae of
the Southern armyworm. Corn leaves treated were added
daily. All treatments were maintained at about 208C in a well
ventilated room. The percent mortality was determined in 5
days.
dichloro-3-nitro-5-¯uorobenzoic acid as described in Sec-
tion 3.3.3. The yellow solid was recrystallized from DMF to
give white ¯ake crystals, yield 49%, mp 167.1±167.88C.
1
Rf ˆ 0:80 (ethyl acetate:petroleum ether ˆ 1:2, v/v). H
NMR (CDCl ): d 8.17 (d, J ˆ 8:44 Hz, 1H), 7.99 (d,
3
H;F
JH;F ˆ 8:79 Hz, 1H), 7.69 (d, J ˆ 6:46 Hz, 1H). Analysis:
H;F
Calc. for C H Cl F N O (441): C, 38.10; H, 0.68; N,
4 2 3 3
1
4
3
9
.52%. Found: C, 37.65; H, 0.66; N, 9.48%.
3.3.8. Preparation of 2-(2,4-dichloro-5-fluorophenyl)-5-(4-
methoxyphenyl)-1,3,4-oxadiazole (IIIh)
Acknowledgements
This compound was prepared as a brown solid from 4-
methoxybenzoic acid as described in Section 3.3.3. The
brown solid was puri®ed on silica gel by column chromato-
graphy with the solvent (petroleum ether:ethyl acetate ˆ
We express our gratitude to the National Natural Science
Foundation of China and Shanghai Foundation of Science
and Technology for the partial ®nancial support.

W. Shi et al. / Journal of Fluorine Chemistry 106 (2000) 173±179
179
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4] X. Ian, J. Tang, W. Chen, R. Gang, Chem. J. Chin. Univ. 15 (1994)
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[5] H. Wu, T. Fan, S. Gang, J. East Chin. Normal Univ. 1 (1980)
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