The synthesis of 1-[(substituted)pyrazol-5-yl]-iminomethyl-2-nitroiminoimidazolidine and its derivatives

Article abstract of DOI:10.1002/jhet.5570380504

In this article 1-[(substituted)pyrazol-5-yl]iminomethyl-2-nitroimino imidazolidines (II) and their derivatives were synthesized. All the compounds were verified by elemental analysis, ¹H NMR and IR. In the reaction of II with halides, two diff

Full text of DOI:10.1002/jhet.5570380504

The Synthesis of 1-[(Substituted)pyrazol-5-yl]-
iminomethyl-2-nitroiminoimidazolidine and its Derivatives
Wei-qiang Chen and Gui-yu Jin*
1035
Sep-Oct 2001
Institute of Elemento-organic Chemistry,
State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, China
Received January 3, 2001
In this article 1-[(substituted)pyrazol-5-yl]iminomethyl-2-nitroimino imidazolidines (II) and their
1
derivatives were synthesized. All the compounds were verified by elemental analysis, H NMR and IR . In
the reaction of II with halides, two different results were observed.
J. Heterocyclic Chem., 38, 1035 (2001).
Introduction.
Results and Discussion.
Synthesis of compounds II
.
2-Nitroiminoimidazolidinyl is a part of the structure of a
new class of insecticide neonicotinoids. Neonicotinoids [1,2]
are a novel and distinct class of insecticides. They combine
selective activity against insects with a favorable safety
profile. Neonicotinoids act as agonists of the nicotinic acetyl-
choline receptor (nAChR) [3,4]. According to the model
a,b
Our studies began with 5-amino-4-cyano(or ethoxy-
carbonyl)-3-methylthio-1-phenyl- pyrazole. There are
two routes to the synthesis of II [6]. In route (I),
reaction of the 5-aminopyrazole with triethyl ortho-
formate, provided the reqired [4-cyano(or ethoxy-
carbonyl)-3-methylthio-1-phenylpyrazol-5-yl]-
iminomethyl ethyl ether (I) (Scheme 1). The reaction of
the imidate I with an equivalent of 2-nitroiminoimida-
a,b
zolidine provided II by the catalysis of BF •Et O in
a,b
3
2
low yield. Excellent yields of II (83-89%) were
a,b
proposed by Yamamoto et al. [5], the distance between N1
and N2 of imidacloprid (IMI) is the major factor for the
activity. By retaining the 2-nitroiminoimidazolidine part in
IMI, our efforts were made to design and synthesize novel
compounds, 1-[(substituted)pyrazol-5-yl]iminomethyl-2-
nitroiminoimidazolidine (II) and their derivatives, in order to
find lead compounds with high bioactivities.
obtained in the presence of sodium hydride. In the
media of Lewis acid and hard base, the imidate I can
changed into 5-aminopyrazole. In the route (II), low
yields of II
were obtained by reaction of the
a,b
corresponding 5-aminopyrazole with 1-diethoxymethyl-
2-nitroiminoimidazolidine in the presence of Lewis acid
or high temperature.

1036
W. Chen and G. Jin
Vol. 38
Synthesis of Compounds II
.
Table 1
Physical Data and Elemental Analysis of Compounds II,III,IV
c-e
The treatment of II with hydrogenperoxide and acetic
b
acid under different condition provided 3-methylsulfinyl
Compound Yield
%
mp.
C°
Elemental Analysis (Calc. %)
II , or 3-methylsulfonyl II (Scheme 2) [7,8,9].
c
e
C
H
N
Synthesis of compounds III and IV.
When II were reacted with iodomethane in the
II
II
II
II
II
III
III
III
III
III
III
IV
IV
IV
IV
IV
IV
89 246-248 48.65(48.64) 4.14(3.81) 29.91(30.25)
84 230-231 48.91(49.00) 4.59(4.58) 23.49(23.21)
74 248-249 46.94(47.11) 4.61(4.42) 22.36(22.62)
65 273-276 44.76(44.71) 3.29(3.51) 27.62(27.84)
67 240-241 45.28(45.43) 4.31(4.26) 21.62(21.83)
60 201-203 49.78(49.99) 4.20(4.20) 29.05(29.15)
30 163-165 52.41(52.41) 4.81(4.89) 27.32(27.17)
68 226-227 50.05(50.11) 5.28(4.91) 22.64(22.72)
22 173-174 52.12(52.28) 5.34(5.48) 21.29(21.34)
56 128-129 53.52(53.26) 5.64(5.75) 20.82(20.70)
48 159-160 48.71(48.87) 5.10(5.13) 19.55(19.95)
31 148-149 63.53(63.44) 4.88(4.84) 20.31(20.18)
40 178-179 54.15(54.26) 4.60(4.55) 21.11(21.09)
34 154-157 61.91(62.18) 5.66(5.46) 15.30(15.11)
22 124-126 54.68(54.89) 4.93(5.18) 15.06(15.24)
63 154-156 54.05(53.92) 4.93(5.20) 15.96(15.72)
68 194-196 55.32(55.36) 4.51(4.65) 16.83(16.84)
a
b
c
d
e
a,b
presence of sodium hydride at room temperature, III
a,c
were obtained respectively. In the same condition, the
treatment of II with bromoalkane did not provide the
a,b
corresponding III, and if the reaction temperature is higher
than 40 °C, the products are 5-aminopyrazole and
a
b
c
d
e
f
2-nitroiminoimidazolidine. III
can be obtained in the
b,d-f
presence of K CO at 60-70 °C in DMSO (Scheme 3).
2
3
a
b
c
d
e
f
Otherwise, the treatment of II with benzyl chloride
a
did not provide the corresponding product III in the
presence of K CO at 60-70 °C in DMSO. The product
2
3
obtained was 3-benzyl-1-(4-cyano-3-methylthio-1-
phenylpyrazol-5-yl)iminomethylimidazolidin-2-one
(IV ) (Scheme 4). The same phenomena were observed
a
in the reaction of II with ethyl bromoacetate, ethyl
b
chloroformate and 2-chloro-5-chloromethylpyridine.

Sep-Oct 2001
The Synthesis of 1-[(Substituted)pyrazol-5-yl]-iminomethyl-2
1037
Table 2
1
The H NMR Data of Compounds II,III,IV
1
Compound
H NMR(DMSO-d ), δ (ppm)
6
II
II
2.56 (s, 3H, CH S), 3.66-3.84 (m, 4H, NCH CH N), 7.32-7.82 (m, 5H, Ph), 8.72 (s, 1H, N=CH)
3 2 2
a
1.28 (t, 3H, CH CH O), 2.48 (s, 3H, CH S), 3.72-3.96 (m, 4H, NCH CH N), 4.16 (q, 2H, OCH CH ), 7.24-7.80 (m, 5H, Ph),
b
3
2
3
2
2
2
3
8.60 (s, 1H, N=CH)
II
1.30 (t, 3H, CH CH ), 3.48 (s, 3H, CH SO), 3.80-3.98 (m, 4H, NCH CH N), 4.15 (q, 2H, OCH CH ,), 7.34-7.76 (m, 5H, Ph),
c
3
2
3
2
2
2
3
8.72 (s, 1H, N=CH)
II
II
3.44 (s, 3H, CH SO ), 3.80-3.96 (m, 4H, NCH CH N), 7.44-7.80 (m, 5H, Ph), 9.02 (s, 1H, N=CH)
d
e
3 2 2 2
1.32 (t, 3H, CH CH ), 3.52 (s, 3H, CH SO ), 3.84-3.96 (m, 4H, NCH CH N), 4.28 (q, 2H, OCH CH ), 7.44-7.84 (m, 5H, Ph),
3
2
3
2
2
2
2
3
8.92 (s, 1H, N=CH)
III
III
2.62 (s, 3H, CH S), 3.06 (s, 3H, N-CH ), 3.98-4.12 (m, 4H, NCH CH N), 7.40-7.80 (m, 5H, Ph), 8.96 (S, 1H, N=CH)
a
3 3 2 2
0.99 (t, 3H, CH CH ), 1.58-1.90 (m, 2H, CH CH CH ), 2.64 (s, 3H, CH S), 3.38 (t, 2H, N-CH CH ), 3.80-4.20 (m, 4H,
b
3
2
3
2
2
3
2
2
NCH CH N), 7.40-7.70 (m, 5H, Ph), 8.84 (s, 1H, N=CH)
2
2
III
III
III
III
1.22 (t, 3H, CH CH O), 2.46 (s, 3H, CH S), 2.96 (s, 3H, CH N), 3.92-4.00 (m, 4H, NCH CH N), 4.15 (q, 2H, OCH CH ),
c
d
e
f
3 2 3 3 2 2 2 3
7.34-7.76 (m, 5H, Ph), 8.72 (s, 1H, N=CH)
0.99 (t, 3H, CH CH ), 1.38 (t, 3H, CH CH O), 1.60-1.92 (m, 2H, CH CH CH ), 2.60 (s, 3H, CH S), 3.42 (t, 2H, CH N),
3
2
3
2
3
2
2
3
2
3.74-4.18 (m, 4H, NCH CH N), 4.34 (q, 2H, OCH CH ), 7.40-7.76 (m, 5H, Ph), 8.80 (s, 1H, N=CH)
2
2
2
3
0.94 (t, 3H, CH CH ), 1.28 (t, 3H, CH CH O), 1.44-1.76 (m, 4H, CH CH CH CH ), 2.54 (s, 3H, CH S), 3.32-3.48 (t, 2H,
3
2
3
2
3
2
2
2
3
C H CH N), 3.96-4.10 (m, 4H, NCH CH N), 4.24 (q, 2H, OCH CH ), 7.44-7.80 (m, 5H, Ph), 8.76 (s, 1H, N=CH)
3
7
2
2
2
2
3
0.92 (t, 3H, CH CH ), 1.32 (t, 3H, CH CH O), 1.60-1.86 (m, 2H, CH CH CH ), 3.38 (s, 3H, CH SO ), 3.38 (t, 2H, CH N),
3
2
3
2
3
2
2
3
2
2
4.04-4.16 (m, 4H, NCH CH N), 4.28 (q, 2H, OCH CH ), 7.42-7.76 (m, 5H, Ph), 8.76 (s, 1H, N=CH)
2
2
2
3
IV
IV
2.64(s, 3H, CH S), 3.36-3.94 (m, 4H, NCH CH N), 4.52 (s, 2H, CH -Ph), 7.56-7.78 (m, 5H, Ph), 8.98 (s, 1H, N=CH)
a
3 2 2 2
1.32 (m, 3H, CH CH ), 2.64 (s, 3H, CH S), 3.88-4.04 (m, 4H, NCH CH N), 4.36 (q, 2H, CH CH ), 7.42-7.78 (m, 5H, Ph), 9.00
b
3
2
3
2
2
2
3
(s, 1H, N=CH)
1.34 (t, 3H, CH CH ), 2.58 (s, 3H, CH S), 3.32-3.50, 3.76-3.94 (m, 4H, NCH CH N), 4.30 (q, 2H, OCH CH ), 4.50 (s, 2H,
IV
IV
IV
IV
c
d
e
f
3
2
3
2
2
2
3
CH -Ph), 7.26-7.78 (m, 10H, Ph,), 8.76 (s, 1H, N=CH)
2
1.34 (double t, 6H, CH CH ), 2.56 (s, 3H, CH S), 3.84-4.02 (m, 4H, NCH CH N), 4.18-4.50 (m, 4H, CH CH ), 7.36-7.76
3
2
3
2
2
2
3
(m, 5H, Ph,), 8.86 (s, 1H, N=CH)
1.32 (m, 6H, CH CH ), 2.60 (s, 3H, CH S), 3.68-4.02 (m, 4H, NCH CH N), 4.12 (s, 2H, CH O-), 4.18-4.44 (m, 4H,
3
2
3
2
2
2
CH CH ), 7.34-7.82 (m, 5H, Ph,), 8.78 (s, 1H, N=CH)
2
3
1.20 (t, 3H, CH CH ), 2.49 (s, 3H, CH S), 3.42-3.51, 3.71-3.80 (m, 4H, NCH CH N), 4.10 (q, 2H, OCH CH ), 4.50 (s, 2H,
3
2
3
2
2
2
3
CH -pyridine), 7.45-7.70 (m, 8H, Ph, pyridine), 8.64 (s, 1H, N=CH)
2
EXPERIMENTAL
Table 3
The IR Data of Compounds II, III,IV
Melting points were determined on Yanco melting point
apparatus and are uncorrected. Element analysis was carried out
on an MF-3 automatic analyzer. The H NMR spectra were
Compound
N-H
CN
C=O
NO
2
1
II
II
II
II
II
3364.5
3354.5
3369.5
3374.5
2214.5
/
/
2229.5
/
2213.5
2211.5
/
/
/
/
2209.5
2206.5
/
/
/
/
/
1526.6 1347.4
1526.5 1357.1
1532.9 1341.7
1533.5 1342.2
1533.3 1340.9
1524.0 1354.8
1523.8 1356.4
1522.5 1354.1
1527.6 1357.4
1529.6 1333.0
1519.9 1342.6
/
a
b
c
d
e
recorded in (CD ) SO solution on Jeol FX-90Q and Bruker
3 2
1674.1
1709.6
/
1709.1
/
AC-P200 spectrometers, and chemical shifts were expressed in
ppm using TMS as the internal reference.
3369.0
Procedure for the Preparation of 1-[(4-Cyano(or ethoxy-
carbonyl)-3-methylthio-1-phenyl)pyrazol-5-yl]iminomethyl-2-
III
III
III
III
III
III
IV
IV
IV
IV
IV
IV
/
/
/
/
/
/
/
/
/
/
/
/
a
b
c
d
e
f
/
nitroiminoimidazolidine II
.
a(b)
1689.7
1689.6
1686.3
1713.5
A solution of [(4-cyano-3-methylthio-1-phenyl)pyrazol-5-
yl]iminomethyl ethyl ether (I ) (0.96 g, 4 mmol) in anhydrous
a
acetonitrile (15mL), was added into a mixture of 2-nitroimino-
imidazolidine (0.52 g, 4 mmol) and 80% sodium hydride (0.18 g,
6 mmol) in anhydrous acetonitrile (15 mL). The mixture was
stirred at room temperature for 3 hours, then the solid was
isolated by filtation. The solid was washed with water, and
purified by silica column chromatography using ethyl
1732.7
a
b
c
d
e
f
1758.8, 1718.1
1734.1, 1690.3
1744.7, 1732.7, 1677.7/
1738.3, 1690.7
1796.6, 1694.7
/
/
/
/
acetate/petroleum ether (2:1) as eluent to give compound II .
a
Procedure for the Preparation of 1-[(4-Ethoxycarbonyl-3-methyl-
sulfinyl-1-phenyl) pyrazol-5-yl]iminomethyl-2-nitroiminoimida-
acetic acid (16.2 mL) was stirred at room temperature for
30 hours. The mixture was diluted with water (50 mL), then the
solid was isolated by filtation. The solid was purified by silica
column chromatography using ethyl acetate/petroleum ether
zolidine (II ).
c
A suspension of 1-[(4-ethoxycarbonyl-3-methylthio-1-
phenyl)pyrazol-5-yl]imino-methyl-2-nitroiminoimidazolidine
(1:1) as eluent to give compound II .
(II ) (0.84 g, 2 mmol) and 30% hydrogenperoxide (3.8 mL) in
c
b

1038
W. Chen and G. Jin
Vol. 38
Procedure for the Preparation of 1-[(4-Ethoxycarbonyl(or
cyano)-3-methylsulfonyl- 1-phenyl)pyrazol-5-yl]iminomethyl-2-
General Procedure for the Preparation of 1-[(1-Phenyl-3-methyl-
thio-4-substituted)pyrazol-5-yl]iminomethyl-3-substituted-
nitroiminoimidazolidine II
.
imidazolidin-2-one IV
.
e(d)
a-f
A suspension of 1-[(4-ethoxycarbonyl-3-methylthio-1-
phenyl)pyrazol-5-yl]imino-methyl-2-nitroiminoimidazolidine
A suspension of II (0.74 g, 2 mmol), benzylchloride (0.38 g,
a
3 mmol), anhydrous potassium carbonate (0.45 g, 3 mmol) and
anhydrous dimethyl sulfoxide (15 mL), was stirred at 60 °C for
16 hours. Then the mixture was poured into ice water (50 mL),
and the solid isolated by filtration. The solid was purified by
column chromatography using petroleum ether/ethyl acetate
(II ) (0.84 g, 2 mmol) and 30% hydrogenperoxide (7.4 mL) in
b
acetic acid (11.7 mL) was stirred at 45-47 °C for 30 hours. The
mixture was diluted with water (50 mL), then filtered. The solid
was purified by silica column chromatography using ethyl
acetate/petroleum ether (1:1) as eluent to give compound II .
d
(1:1) as eluent to give IV .
a
General Procedure for the Preparation of 1-[(4-Cyano(or ethoxy-
carbonyl)-3-methyl-thio-1-phenyl)pyrazol-5-yl]iminomethyl-3-
Acknowledgements.
methyl-2-nitroiminoimidazolidine III
.
This work was supported by the National Natural Science
Foundation of China (29832050).
a(c)
To a solution of 1-[(4-cyano-3-methylthio-1-phenyl)pyrazol-5-
yl]iminomethyl- 2-nitroiminoimidazolidine (II ) (0.74 g,
a
REFERENCES AND NOTES
2 mmol) in anhydrous dimethyl sulfoxide (15 mL), 80% sodium
hydride (0.12 g, 4 mmol) was added. After 0.5 hours,
iodomethane (0.46 g, 3 mmol) was added. The mixture was
stirred at room temperature for 10 hours. Then the mixture was
poured into 50 mL ice water. After filtration, the residue was
purified by silica column chromatography using ethyl
[*]
To whom correspondence should be addressed.
Email: chwqiang@mail.zlnet.com.cn
[1] K. Shiokawa, S. Tsuboi and S. Kagabu, European Patent
1,92,060 (1986).
acetate/petroleum ether (1:1) as eluent to give III .
[2] Yamamoto, Agrochem. Jpn., 68, 14 (1996).
[3] M. Tomizawa and I. Yamamoto, J. Pestic. Sci., 17, 231
(1992).
[4] A. Nakayama and M. Sukekawa, Pestic. Sci., 52, 104 (1998).
[5] S. Kagabu, J. Pestic. Sci., 21, 231 (1996).
[6] K. Kodaka, K. Kinoshita, M. Nakaya, K. Ebihara, S. Shirashi,
E. Yamada and S. Numata, Europe Patent 0,490,323 A1 (1991).
[7] R. J. Lu, Dissertation, Institute of Elemento-Organic
Chemistry, Nankai University (1995).
a
General Procedure for the Preparation of 1-[(1-Phenyl-3-
methylthio-4-substituted)pyrazol-5-yl]iminomethyl-3-substi-
tuted-2-nitroiminoimidazolidine III
.
b,d-f
A suspension of II (0.74 g, 2 mmol), 1-bromopropane (0.25 g,
a
2 mmol), anhydrous potassium carbonate (0.45 g, 3 mmol) and
anhydrous dimethyl sulfoxide (15 mL), was stirred at 60 °C for
16 hours. Then the mixture was poured into ice water (50 mL),
and the solid isolated by filtration. The solid was purified by
column chromatography using petroleum ether/ethyl acetate
[8] R. Ogura, G. Tsuchihashi, Bull. Chem. Boc. Japan, 45, 2203
(1973).
[9] M. S. Abbady, Phosphorus, Sulfur and Silicon, 68, 69 (1992).
(1:1) as eluent to give III .
b