Synthesis and insecticidal activities of novel 1H-pyrazole-5-carboxylic acid derivatives

Article abstract of DOI:10.1515/hc-2017-0110

Fourteen 1H-pyrazole-5-carboxylic acid derivatives containing oxazole and thiazole rings were synthesized and characterized by ¹H NMR, mass spectrometry and elemental analysis. Most target compounds were obtained in overall yields in the range of 30-50%. The insecticidal activities of these new compounds against Aphis fabae were evaluated. The bioassays' results indicate that some of these compounds exhibit good activities, especially compound 7h which shows 85.7% mortality against A. fabae at a concentration of 12.5 mg/L. This activity is comparable to that of the commercial insecticide imidacloprid.

Full text of DOI:10.1515/hc-2017-0110

Heterocycl. Commun. 2017; aop
Danling Huang, Aiping Liu*, Weidong Liu*, Xingping Liu, Yeguo Ren, Xi Zheng, Hui Pei,
Jun Xiang, Mingzhi Huang and Xiaoguang Wang
Synthesis and insecticidal activities of novel
1
H-pyrazole-5-carboxylic acid derivatives
https://doi.org/10.1515/hc-2017-0110
core structure into pesticide molecules for the purpose of
improving bioactivity [6–9]. Oxazole and thiazole rings
have also gained importance in the agrochemical field.
There are many oxazole and thiazole derivatives being
developed commercially, such as famoxadone, metami-
fop, ethaboxam and trifluzamide [10–13]. In our previ-
ous work, a series of 1H-pyrazole-5-carboxamide and
thiazole derivatives had been designed and synthesized,
but their bioactivities were unsatisfactory [14–17]. Insec-
ticidal activities of new compounds synthesized as part
of this work were tested at the concentration of 500 mg/L
against the target pests Aphis fabae, Mythimna separata
and spider mites. The results of the preliminary bioassay
show that the compounds are active against Aphis fabae
Received June 6, 2017; accepted September 21, 2017
Abstract: Fourteen 1H-pyrazole-5-carboxylic acid deriva-
tives containing oxazole and thiazole rings were synthe-
1
sizedandcharacterizedby HNMR, massspectrometryand
elemental analysis. Most target compounds were obtained
in overall yields in the range of 30–50%. The insecticidal
activities of these new compounds against Aphis fabae
were evaluated. The bioassays’ results indicate that some
of these compounds exhibit good activities, especially
compound 7h which shows 85.7% mortality against A. fabae
at a concentration of 12.5 mg/L. This activity is compara-
ble to that of the commercial insecticide imidacloprid.
Keywords: insecticidal activity; oxazole; pyrazole; struc- only. A subsequent bioassay against A. fabae at a lower
ture-activity relationship; thiazole.
concentration was carried out.
Introduction
Results and discussion
The pyrazole ring plays an important role in drug design In this work, in the search for novel compounds with
1]. In particular, 1H-pyrazole-5-carboxamide derivatives insecticidal activity, several pyrazole carboxylic acid
[
have been the focus of increasing interest over the past derivatives were designed guided by the lead com-
decades because of their low toxicity and high bioactiv- pound tebufenpyrad. As shown in Figure 1, an oxazole
ity [2–4]. For instance, the commercial product tebufen- or thiazole ring (moiety A) was introduced into the
pyrad (Figure 1) displays excellent insecticidal activity [5] 1H-pyrazole-5-carboxamide. The group on pyrazole
and pyrazole-5-carboxylic acid is often incorporated as a ring (moiety B) was altered and the amide group was
replaced with an ester group (moiety C). All target com-
pounds 7a–n were synthesized as shown in Scheme 1
1
and characterized using H nuclear magnetic resonance
*
Corresponding authors: Aiping Liu and Weidong Liu, National
(
NMR), mass spectroscopy (MS) and elemental analysis.
Preparation of key intermediates was similar to our pre-
vious work [18].
The insecticidal activities against A. fabae of com-
pounds 7 are shown in Table 1. The data indicate that most
of the compounds show excellent activity at 500 mg/L and
Engineering Research Center for Agrochemicals, Hunan Research
Institute of Chemical Industry, Changsha 410007, China; and
Hunan Province Key Laboratory for Agrochemicals, Changsha
4
10014, China, e-mail: lapliu@yahoo.com (A. Liu);
liuweidonghn@yahoo.com.cn (W. Liu)
Danling Huang, Xi Zheng and Xiaoguang Wang: National
Engineering Research Center for Agrochemicals, Hunan Research
Institute of Chemical Industry, Changsha 410007, China; and College some of them display potent activity at lower concentra-
of Chemistry and Chemical Engineering, Hunan Normal University,
Changsha 410081, China
tion. For example, the mortality of 7f, 7h and 7i against
A. fabae at 200 mg/L remains 100%. Compound 7h
induces mortality greater than 80% against A. fabae at a
concentration of 12.5 mg/L and this activity is comparable
to that of the commercial insecticide imidacloprid (89.8%
mortality against A. fabae).
Xingping Liu, Yeguo Ren, Hui Pei, Jun Xiang and Mingzhi Huang:
National Engineering Research Center for Agrochemicals, Hunan
Research Institute of Chemical Industry, Changsha 410007, China;
and Hunan Province Key Laboratory for Agrochemicals, Changsha
4
10014, China
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ꢀꢀꢀꢀꢁꢀD. Huang et al.: Novel pyrazolecarboxylic insecticides
N
B
W
A
O
R1
N
O
Cl
O
Cl
N
N
X
Ar
N
N
H
H
Ar
N
N
Optimization
program
N
W
N
N
C
W
A
Tebufenpyrad
Figure 1ꢀDesign strategy of the target compounds.
Target compound
O
O
O
N
O
O
N
O
O
CH3CH2ONa
CH3NHNH2
°C, 2 h
N
SO Cl , ClCH CH Cl
2
2
2
2
N
O
O
O
0
Acetone, –5°C, 3 h
∆, 2 h
O
O
Cl
8
1a
1b
N
O
N
O
N
O
N
1. H2O,NaOH
. H+
N
SOCl2, ClCH2CH2Cl
N
1
1
–3a: R1 = H
–3b: R = Cl
O
OH
2a,b
Cl
2
∆, 2 h
1
R1
R1
R1
1a,b
3a,b
O
NK
O
O
Hydrazine
hydrate
W
W
N
W
N
W
Cl
Cl
O
Ar
Ar
Ar
N
Cl
N
NH2
Ar
NH2
O
4a–e
5a–e
6a–e
O
N
10% NaOH solution
Ar
6f: Ar = 2-Cl-C6H4; W = O
OH 6g: Ar = 2,6-diF-C H ; W= O
6
4
6
f,g
1
1
4
4
4
–6a:R = H; Ar = Ph; W = O
4–6b:R = Cl; Ar = Ph; W = S
1
1
–6c:R = H; Ar = 2-Cl-C6H4; W = O
4–6d:R = Cl; Ar = 2-Cl-C H ; W = S
6
4
1
–6e:R = H; Ar = 2,6-diF-C6H4; W = O
R1
O
W
N
Et3N
N
Ar
3a,b + 6a–g
X
N
7
a–n
1
7
7
7
7
7
7
7
a: R1 = H; Ar = Ph; X = NH; W = O
7h: R = Cl; Ar = Ph; X = NH; W = O
1
1
b: R = H; Ar = Ph; X = NH; W = S
7i: R = Cl; Ar = Ph; X = NH; W = S
1
1
c: R = H; Ar = 2-Cl-C6H4; X = NH; W = O
7j: R = Cl; Ar = 2-Cl-C6H4; X = NH; W = O
1
1
d: R = H; Ar = 2-Cl-C6H4; X = O; W = O
7k: R = Cl; Ar = 2-Cl-C6H4; X = O; W = O
1
1
e: R = H; Ar = 2-Cl-C6H4; X = NH; W = S
7l: R = Cl; Ar = 2-Cl-C H ; X = NH; W = S
6
4
1
1
f: R = H; Ar = 2,6-diF-C6H; X = NH; W = O
7m: R = Cl; Ar = 2,6-diF-C6H; X = NH; W = O
1
1
g: R = H; Ar = 2,6-diF-C6H; X = O; W = O
7n: R = Cl; Ar = 2,6-diF-C6H; X = O; W = O
Scheme 1ꢀSynthesis of target compounds 7a–n.
The structure-activity relationship appears to be fol- than carboxylate ester counterparts. For example, com-
lowing a general trend. On the basis of the bioassay data, pounds 7c and 7j are much more active than 7d and 7k,
1
the substituents R , Ar, X and W show a significant rela- respectively.
1
tionship with the activity. When R , Ar and W are kept
constant, the influence of X on the insecticidal activi-
ties shows a regular change. The insecticidal activities Conclusions
of the target compounds increase when the X is an NH
rather than O moiety. More specifically, in the substi- In the search for potent insecticidal agents, a series of
tuted pyrazoles, amide derivatives display better activities 1H-pyrazole-5-carboxylic acid derivatives (esters and
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D. Huang et al.: Novel pyrazolecarboxylic insecticidesꢂꢁꢀꢀꢀꢂ3
Table 1ꢀActivities against Aphis fabae of compounds 7.
slowly and the solution was stirred below 0°C for 2 h. The solvent
was removed under reduced pressure and the aqueous phase was
Compound
Mortality rate against A. fabae (%) extracted with ethyl acetate. The organic layer was washed twice
with water and dried over Na SO , filtered, and concentrated under
2
4
ꢁ00 mg/L
ꢂ00 mg/L
ꢁ0 mg/L
ꢃꢂ.ꢁ mg/L
reduced pressure to yield 39.3 g (92% yield, 90% purity) of a yellow
ꢄa
93.ꢃ
ꢇꢄꢄ.ꢄ
ꢉ9.ꢊ
9ꢄ.ꢅ
ꢈꢃ.ꢅ
ꢃꢆ.ꢅ
–
ꢆꢅ.ꢆ
3ꢈ.ꢃ
ꢈ9.ꢇ
–
3ꢆ.ꢅ oil (ref. [19] indicates this as a colorless solid, mp 40–42°C). With-
3ꢆ.ꢄ out further purification, compound 1a was used in the next reaction.
ꢄb
ꢄc
ꢇꢆ.ꢃ The NMR data of 1a and the literature values [19] are virtually identi-
1
ꢄd
ꢅꢆ.ꢄ
–
cal. H NMR (CDCl ): δ 1.37 (t, Jꢁ=ꢁ7.15 Hz, 3H, CH ), 2.26 (d, Jꢁ=ꢁ0.40 Hz,
3
3
ꢄe
9ꢈ.ꢃ
ꢃꢈ.ꢇ
ꢇꢄꢄ.ꢄ
ꢊꢉ.3
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
9ꢆ.3
–
ꢈꢇ.ꢃ
ꢅꢆ.ꢅ
ꢆꢄ.3
9ꢇ.ꢇ
ꢆꢊ.9
ꢉꢈ.ꢃ
–
3ꢃ.3 3H, CH ), 4.11 (s, 3H, CH ), 4.32 (q, Jꢁ=ꢁ7.15 Hz, 2H, CH ), 6.61 (q, 1 H;
3
3
2
ꢄf
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢆꢊ.ꢉ
ꢃ.ꢃ
ꢇꢆ.ꢃ
ꢃꢆ.ꢉ
3ꢅ.9
ꢈꢊ.ꢉ
–
13
Jꢁ=ꢁ0.40 Hz; CH); C NMR (CDCl ): δ 160.0, 146.9, 133.0, 110.4, 60.8, 39.1,
3
ꢄg
1
4.3, 13.3.
ꢄh
ꢄi
ꢄj
ꢄk
Synthesis of ethyl 1,3-dimethyl-4-chloro-1H-pyrazole-
-carboxylate (1b)
ꢄl
9ꢃ.3
ꢃꢉ.ꢄ
–
ꢉꢃ.ꢊ
–
ꢆꢆ.ꢊ
–
5
ꢄm
3ꢄ.ꢄ
ꢄn
ꢆꢊ.ꢉ
–
–
–
SO Cl (8.04 g, 0.06 mol) was slowly added to a stirred solution of 1a
Imidacloprid
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢇꢄꢄ.ꢄ
ꢃ9.ꢃ
2
2
(
10 g, 0.06 mol) in dichloroethane (50 mL) in an ice bath and the mix-
ture was stirred under reflux for 2 h. The solvent was removed under
reduced pressure and the residue was treated with an aqueous solu-
amides) were designed and synthesized. Most of the com- tion of NaCl. The mixture was extracted with ethyl acetate, washed
twice with water, dried over Na SO , filtered, and concentrated under
reduced pressure to yield 10.0 g (95% yield, 88% purity) of a brown
liquid.
pounds display good insecticidal activity against A. fabae.
The best compound 7h displays 85.7% mortality rate at
concentration of 12.5 mg/L.
2
4
Synthesis of compounds 2a,b
Experimental
Melting points were measured on a WPS-1B melting-point apparatus
Compound 1a (0.05 mol) was added to a solution of NaOH (6.0 g,
0
.15 mol) in water (100 mL). After 4 h at 80°C, the mixture was
(
made in Shanghai Physical Optics Instrument Plant) and are uncor-
1
poured into ice water and adjusted to an acidic pH. The resulting
precipitate was filtered and dried to yield 4.6 g (60% yield, 92%
purity) of a white solid. Compound 2b was synthesized in a similar
way.
rected. H NMR spectra were recorded in CDCl on a Varian INOVA-300
3
instrument using trimethylsilyl (TMS) as the internal standard. High
resolution mass spectra were acquired using an Agilent 5973-6890
gas chromatography-mass spectrometer (GC-MS) and an Agilent
1
100 liquid chromatography-mass spectrometer (LC-MS). Column
1
,3-Dimethyl-1H-pyrazole-5-carboxylic acid (2a)ꢂWhite solid;
chromatography was performed using 200–300 mesh silica gel.
1
mp 172.6–172.9°C; H NMR (DMSO-d ): δ 2.26 (s, 3H, CH ), 4.11 (s, 3H,
6
3
CH ), 6.61 (s, 1H, pyrazole-H), 6.66 (bs, 1H, NH), 12.75 (bs, 1H, COOH);
3
+
LC-MS: m/z 140, [Mꢁ+ꢁ1] . Anal. Calcd for C H lN O : C, 51.42; H, 5.75; N,
Synthesis of ethyl 2,4-dioxovalerate (8)
6
8
2
2
1
9.99; Found: C, 51.44; H, 5.71; N, 20.01.
A solution of sodium ethoxide (30.0 g, 0.45 mol) in anhydrous ethanol
4
-Chloro-1,3-dimethyl-1H-pyrazole-5-carboxylic acid (2b)ꢂWhite
(
300 mL) was maintained at −5°C and slowly treated for 3 h with a solu-
1
solid, mp 216–217°C; H NMR (DMSO-d ): δ 2.24 (s, 3H, CH ), 4.14 (s,
6
3
tion of diethyl oxalate (46.7 g, 0.32 mol) in acetone (14.7 g, 0.3 mol).
The mixture was then poured into ice water, and after acidification
with 1 ꢀ hydrochloric acid to pH 4 the aqueous phase was extracted
with ethyl acetate. The extract was washed twice with water, dried
over Na SO , filtered and concentrated under reduced pressure to give
+
3
H, CH ), 12.75 (bs, 1H, COOH); LC-MS: m/z 174, [Mꢁ+ꢁ1] . Anal. Calcd
3
for C H ClN O : C, 41.28; H, 4.04; N, 16.05; Found: C, 41.22; H, 4.10;
6
7
2
2
N, 15.96.
2
4
4
6.5 g (94% yield, 96% purity) of a yellow liquid. Without further puri-
fication, compound 8 was used in the subsequent reaction.
Synthesis of 1,3-dimethyl-1H-pyrazolecarbonyl chloride
3a) and its analogue 3b
(
Synthesis of ethyl 1,3-dimethyl-1H-pyrazole-5-
A mixture of 2a (0.01 mol) and thionyl chloride (2.95 g, 0.025 mol) in
,2-dichloroethane (15 mL) was heated under reflux for 2 h and then
concentrated under reduced pressure. Without further purification,
carboxylate (1a)
1
In 300 mL of anhydrous ethanol was dissolved 8 (46.5 g) with stirring the next reaction was carried out immediately. Compound 3b was
below −5°C. Then, aqueous methylhydrazine (0.38 mol) was added synthesized by using a similar procedure.
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ꢀꢀꢀꢀꢁꢀD. Huang et al.: Novel pyrazolecarboxylic insecticides
Synthesis of 4-(chloromethyl)-2-phenyloxazole (4a)
and its analogues 4c and 4e
Synthesis of 4-(hydroxymethyl)-2-aryloxazoles 6f,g
A mixture of 4a (0.01 mol), aqueous solution of NaOH (4 g, 10%) and
THF (20 mL) was heated under reflux for 4 h, then cooled and con-
centrated under reduced pressure. The residue was treated with ethyl
acetate (150 mL) and hydrochloric acid (10%, 100 mL). The organic
A mixture of benzamide (18.15 g, 150 mmol) and 1,3-dichloro-
acetone (19 g, 170 mmol) was ground thoroughly. Then the mixture
was melted and the temperature was kept at 130°C for 2 h. After
cooling to room temperature, 150 mL of ethyl acetate was added
and the mixture was washed twice with saturated Na CO solution.
layer was dried over Na SO , filtered, and concentrated to furnish
2
4
0
.99g (50% yield, 89% purity) of 6f as a colorless oil. Without further
2
3
purification, the product was used in the subsequent reaction. The
The organic solution was dried over Na SO , filtered and concen-
2
4
analogue 6g was synthesized in a similar way.
trated to furnish 25.3 g (94% purity) of 4a as a yellow oil: yield
9
8%. Without further purification, the product 4a was used in the
1
(
2-(2-Chlorophenyl)oxazol-4-yl)methanol (6f)ꢂ H NMR (DMSO-
next reaction. The analogues 4c and 4e were synthesized in a simi-
d ): δ 4.61 (s, 2H, CH ), 7.36–7.49 (m, 3H), 7.77 (s, 1H), 7.97–7.91 (m, 1H),
lar way.
6
2
+
8
5
.29 (s, 1H); LC-MS: m/z 210, [Mꢁ+ꢁ1] . Anal. Calcd for C H ClNO : C,
10 8 2
7.30; H, 3.85; N, 6.68. Found: C, 57.22; H, 4.88; N, 6.60.
Synthesis of 4-(chloromethyl)-2-phenylthiazole (4b)
and its analogue 4d
Synthesis of compounds 7a–n
A solution of thiobenzamide (20.5 g, 150 mmol) and 1, 3-dichloro-
acetone (19 g, 170 mmol) in ethanol (150 mL) was heated to reflux
for 2 h. After cooling to room temperature, the solvent was removed
under reduced pressure and the residue was treated with ethyl ace-
tate (150 mL) and water (100 mL). The organic layer was dried over
Na SO , filtered, and concentrated to yield 29.1 g (90% yield, 88%
purity) of 4b as a yellow oil. Without further purification, the product
was used in the next reaction. The analogue 4d was synthesized in
a similar way.
Compound 3a (0.01 mol) was added dropwise to a solution of 6a
(
0.01 mol) and triethylamine (0.02 mol) in THF (20 mL) at 0°C. The
2
mixture was allowed to stand overnight, then poured into Na CO3
solution and the aqueous phase was extracted with ethyl acetate. The
extract was dried, filtered and concentrated. The residue was sub-
jected to silica gel chromatography eluting with a gradient of petro-
leum ether-ethyl acetate (10:1/5:1) to yield 7a. Compounds 7b–n were
synthesized in a similar manner.
2
4
1
,3-Dimethyl-N-[(2-phenyloxazol-4-yl)methyl]-1H-pyrazole-
5-carboxamide (7a)ꢂYield 42.6% of a gray solid, mp 104–106°C;
Synthesis of compounds 6a–e
1
H NMR (CDCl ): δ 2.25 (s, 3H), 4.11 (s, 3H), 4.55 (dd, Jꢁ=ꢁ1.2 Hz,
3
Jꢁ=ꢁ5.4 Hz, 2H), 6.34 (s, 1H,), 6.66 (bs, 1H), 7.44–7.49 (m, 3H), 7.69 (t,
+
To a solution of 4a (0.045 mol) in N,N-dimethylformamide (DMF, Jꢁ=ꢁ0.9 Hz, 1H), 8.01–8.01 (m, 2H); GC-MS: m/z 296, M , base peak at
1
00 mL), potassium phthalimide (0.05 mol) was added portion- m/z 173. Anal. Calcd for C H N O : C, 64.85; H, 5.44; N, 18.91. Found:
16 16 4 2
wise. The mixture was stirred at 80°C for 5 h, poured into ice water C, 64.55; H, 5.42; N, 18.93.
and the resultant precipitate was collected by filtration and washed
with water to furnish 5a as brown solid. A mixture of 5a thus 1,3-Dimethyl-N-[(2-phenylthiazol-4-yl)methyl]-1H-pyrazole-
obtained, ethanol (200 mL) and hydrazine hydrate (80%, 6.25 g, 5-carboxamide (7b)ꢂYield 38% of a yellow solid; mp 105–106°C;
1
0.1 mol) was heated under reflux for 5 h, and the resultant precipi-
H NMR (CDCl ): δ 2.26 (s, 3H), 4.11 (s, 3H), 4.70 (dd, Jꢁ=ꢁ5.7, 0.9 Hz,
3
tate was separated by filtration and the filtrate was concentrated 2H), 6.35 (s, 1H), 6.76 (bs, 1H), 7.20 (s, 1H), 7.43–7.49 (m, 3H), 7.91–7.97
1
3
under reduced pressure. The residue was treated with cold water (m, 2H); C NMR (CDCl , 75 MHz): δ 168.8, 159.8, 153.2, 146.5, 135.4,
3
and the mixture was extracted with ethyl acetate. The extract was 133.1, 129.9, 128.9, 126.3, 115.4, 105.8, 39.4, 38.7, 13.1; GC-MS: m/z 312,
+
washed twice with water, dried over Na SO and concentrated under M , base peak at m/z 189. Anal. Calcd for C H N OS: C, 61.52; H, 5.16;
2
4
16 16
4
reduced pressure to furnish 5.2 g (78% yield, 85% purity) of 6a as N, 17.93. Found: C, 61.41; H, 5.13; N, 18.03.
a brown oil. Without further purification, the product was used in
the subsequent reaction. The analogues 6b–e were synthesized in N-[(2-(2-Chlorophenyl)oxazol-4-yl)methyl]-1,3-dimethyl-
1
a similar way.
1H-pyrazole-5-carboxamide (7c)ꢂYield 42% of a brown oil; H NMR
(CDCl ): δ 2.26 (s, 3H), 4.13 (s, 3H), 4.57 (d, Jꢁ=ꢁ5.4 Hz, 2H), 6.33 (s, 1H),
3
1
(
4
2-Phenyloxazol-4-yl)methanamine (6a)ꢂ H NMR (DMSO-d ): δ 6.66 (bs, 1H), 7.34–7.54 (m, 3H), 7.77 (s, 1H), 7.94–7.97 (m, 1H); GC-MS:
6
+
.01 (s, 2H, CH ), 7.56–7.59 (m, 3H, Ph H), 7.98–8.02 (m, 2H, Ph H), m/z 300, M , base peak at m/z 207. Anal. Calcd for C H ClN O : C,
2 16 15 4 2
+
8
.29(s, 1H, oxazole-H), 8.58 (bs, 2H, NH); LC-MS: m/z 175, [Mꢁ+ꢁ1] . 58.10; H, 4.57; N, 16.94. Found: C, 58.02; H, 4.66; N, 16.87.
Anal. Calcd for C H N O: C, 68.95; H, 5.79; N, 16.08. Found: C, 68.99;
1
0
10
2
H, 5.84; N, 15.98.
(2-(2-Chlorophenyl)oxazol-4-yl)methyl1,3-dimethyl-1H-pyrazole-
5
-carboxylate (7d)ꢂYield 10% of a white solid; mp 86–87°C;
1
1
(2-Phenylthiazol-4-yl)methanamine (6b)ꢂ H NMR (DMSO-d ):
H NMR (CDCl ): δ 2.25 (s, 3H), 4.12 (s, 3H), 5.32 (d, Jꢁ=ꢁ0.6 Hz, 2H),
6
3
δ 4.18 (s, 2H, CH ), 7.49–7.56 (m, 3H, Ph H), 7.84 (s, 1H, thiazole-H), 6.62 (d, Jꢁ=ꢁ0.6 Hz, 1H), 7.33–7.52 (m, 3H), 7.77 (t, Jꢁ=ꢁ0.6 Hz, 1H), 7.96–
2
+
+
7
.97–7.99(m, 2H, Ph H), 8.59 (bs, 2H, NH); LC-MS: m/z 191, [Mꢁ+ꢁ1] . 7.99 (m, 1H); GC-MS: m/z 331, M , base peak at m/z 208. Anal. Calcd
Anal. Calcd for C H N S: C, 63.13; H, 5.30; N, 14.72. Found: C, 63.10; for C H ClN O : C, 57.93; H, 4.25; N, 12.67. Found: C, 57.86; H, 4.32;
1
0
10
2
16 14
3
3
H, 5.27; N, 14.81.
N, 12.63.
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D. Huang et al.: Novel pyrazolecarboxylic insecticidesꢂꢁꢀꢀꢀꢂ5
N-[(2-(2-Chlorophenyl)thiazol-4-yl)methyl]-1,3-dimethyl-1H- 4-Chloro-N-[(2-(2,6-difluorophenyl)oxazol-4-yl)methyl]-1,3-di-
pyrazole-5-carboxamide (7e)ꢂYield 48% of a yellow solid; mp methyl-1H-pyrazole-5-carboxamide (7m)ꢂYield 35% of a yellow
1
1
1
09–110°C; H NMR (CDCl ): δ 2.27 (s, 3H), 4.17 (s, 3H), 4.74–4.76 (m, solid; mp 125–127°C; H NMR (CDCl ): δ 2.13 (s, 3H), 2.17 (s, 3H), 4.02
3
3
2
H), 6.33 (s, 1H), 6.76 (bs, 1H), 7.35–7.53 (m, 3H), 7.42 (s, 1H), 8.16–8.20 (s, 3H), 4.62 (dd, Jꢁ=ꢁ5.7 Hz and 0.9 Hz, 2H), 6.49 (bs, 1H), 7.01–7.09 (m,
+
+
(
m, 1H); GC-MS: m/z 346, M , base peak at m/z 223. Anal. Calcd for 2H), 7.40–7.49 (m, 1H), 7.82 (t, Jꢁ=ꢁ0.9 Hz, 1H); GC-MS: m/z 346, M , base
C H ClN OS: C, 55.41; H, 4.36; N, 16.15. Found: C, 55.37; H, 4.41; peak at m/z 209. Anal. Calcd for C H ClF N O : C, 52.40; H, 3.57; N,
1
6
15
4
16 13
2
4
2
N, 16.18.
15.28. Found: C, 52.33; H, 3.55; N, 15.36.
N-[(2-(2,6-Difluorophenyl)oxazol-4-yl)methyl]-1,3-dimethyl-1H- [2-(2,6-Difluorophenyl)oxazol-4-yl]methyl-4-chloro-1,3-di-
pyrazole-5-carboxamide (7f)ꢂYield 39% of a yellow solid; mp 145– methyl-1H-pyrazole-5-carboxylate (7n)ꢂYield 32% of a gray solid;
1
1
1
46°C; H NMR (CDCl ): δ 2.25 (s, 3H), 4.113 (s, 3H), 4.57 (dd, Jꢁ=ꢁ5.4, mp 149–150°C; H NMR (CDCl ): δ 2.24 (s, 3H), 4.10 (s, 3H), 5.42 (d,
3
3
0
.9, 2H), 6.31 (s, 1H), 6.96 (bs, 1H), 7.02–7.08 (m, 2H), 7.42–7.48 (m, 1H), Jꢁ=ꢁ0.9 Hz, 2H), 7.02–7.09 (m, 2H), 7.42–7.47 (m, 1H), 7.96 (s, 1H); GC-MS:
+
+
7
.82 (s, 1H); GC-MS: m/z 332, M , base peak at m/z 209. Anal. Calcd m/z 367, M , base peak at m/z 166. Anal. Calcd for C H ClF N O : C,
16 12 2 3 3
for C H F N O : C, 57.83; H, 4.25; N, 16.86. Found: C, 57.78; H, 4.32; 52.26; H, 3.29; N, 11.43. Found: C, 52.20; H, 3.34; N, 11.40.
1
6
14
2
4
2
N, 16.82.
[
2-(2,6-Difluorophenyl)oxazol-4-yl)methyl]
1,3-dimethyl-1H-
pyrazole-5-carboxylate (7g)ꢂYield 24% of a yellow solid; mp 97– Biological assay
1
9
8°C; H NMR (CDCl ): δ 2.36 (s, 3H), 4.123 (s, 3H), 5.34 (d, Jꢁ=ꢁ0.9Hz,
3
2
H), 6.66 (s, 1H), 7.02–7.08 (m, 2H), 7.42–7.47 (m, 1H),7.90 (s, 1H); GC-MS:
Stock solution of every test compound was prepared in
DMF at a concentration of 1.0 g /L and then diluted to the
required concentration (12.5–500 mg/L) with water con-
taining Tween 80 (0.4 mg/L).
The horse bean seedlings with A. fabae were dipped
in the test solution for 5–10 s, then allowed to dry with a
filter paper, transferred to a beaker (100 mL) containing
water (10 mL) and kept at 25°C. Each assay consisted of
three analyses. After 24 h, mortalities were recorded and
the results were averaged.
+
m/z 333, M , base peak at m/z 166. Anal. Calcd for C H F N O : C,
16
13
2
3
3
5
7.66; H, 3.93; N, 12.61. Found: C, 57.70; H, 3.88; N, 12.60.
4
-Chloro-1,3-dimethyl-N-[(2-phenyloxazol-4-yl)methyl]-1H-
pyrazole-5-carboxamide (7h)ꢂYield: 39% of a white solid; mp
1
1
23–124°C; H NMR (CDCl ): δ 2.24 (s, 3H), 4.13 (s, 3H), 4.61 (dd, Jꢁ=ꢁ5.4,
3
0
.9 Hz, 2H), 7.34 (bs, 1H), 7.45–7.50 (m, 3H), 7.71 (s, 1H), 8.01–8.06
+
(
m, 2H); GS-MS: m/z 330, M , base peak at m/z 173. Anal. Calcd for
C H ClN O : C, 58.10; H, 4.57; N, 16.94. Found: C,58.14; H, 4.50;
N, 16.99.
1
6
15
4
2
4
-Chloro-1,3-dimethyl-N-[(2-phenylthiazol-4-yl)methyl]-1H-
pyrazole-5-carboxamide (7i)ꢂYield 30% of a white solid; mp
Acknowledgments: We gratefully acknowledge the finan-
cial support from the National Natural Science Founda-
tion of China (No. 21572050 and No. 21672057).
1
1
36–137°C; H NMR (CDCl ): δ 2.25 (s, 3H), 4.144 (s, 3H), 4.78 (dd,
3
Jꢁ=ꢁ5.1, 0.6 Hz, 2H), 7.21 (s, 1H), 7.43–7.48 (m, 3H), 7.58 (bs, 1H), 7.92–
+
7
.97 (m, 2H); GC-MS: m/z 346, M , base peak at m/z 189. Anal. Calcd
for C H ClN OS: C, 55.41; H, 4.36; N, 16.15. Found: C, 55.47; H, 4.29;
1
6
15
4
N, 16.20.
References
4
-Chloro-N-[(2-(2-chlorophenyl)oxazol-4-yl)methyl]-1,3-di-
methyl-1H-pyrazole-5-carboxamide (7j)ꢂYield 32% of a white
[
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1] Sener, A.; Kasimogullari, R.; Sener, M. K.; Bildirici, I.; Akca-
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3
(
dd, Jꢁ=ꢁ5.7, 0.6 Hz, 2H), 7.34 (bs, 1H), 7.34–7.42 (m, 2H), 7.50–7.53 (m,
+
1
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4
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14
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4
2
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1
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(
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3
+
(
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1
6
13
2
3
3
3
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4
-Chloro-N-[(2-(2-chlorophenyl)thiazol-4-yl)methyl]-1,3-di-
methyl-1H-pyrazole-5-carboxamide (7l)ꢂYield 31% of a white
1
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3
Jꢁ=ꢁ5.4 Hz, 2H), 7.38–7.42 (m, 3H), 7.51 (s, 1H), 7.64 (bs, 1H, NH), 8.31 (d,
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+
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16
13
2
3
2
C, 50.40; H, 3.70; N, 14.69. Found: C, 50.43; H, 3.78; N, 14.64.
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6
ꢀꢀꢀꢀꢁꢀD. Huang et al.: Novel pyrazolecarboxylic insecticides
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