Reactions of [(4-cyano-3-methylsulfanyl-1-phenyl)pyrazol-5-yl]iminomethylenyl ethyl ether with compounds containing amino group and the bioactivity of products

Article abstract of DOI:10.1080/10426500211705

The study on reaction of (1-phenyl-3-methylthio-4-cyanopyrazol-5-yl)-iminomethylene ethyl ether with compounds containing amino group was discussed in order to understand its reactivity. Some structures of compounds were verified by x-ray crystallographic

Full text of DOI:10.1080/10426500211705

This article was downloaded by: [University of Windsor]
On: 25 September 2013, At: 04:18
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Reactions of [(4-cyano-3-methylsulfanyl-1-
phenyl)pyrazol-5-yl]iminomethylenyl Ethyl Ether
with Compounds Containing Amino Group and the
Bioactivity of Products
Wei-Qiang Chen a & Gui-Yu Jin a
a Institute of Elemento-Organic Chemistry, State Key Laboratory of Elemento-Organic
Chemistry, Nankai University, Tianjin, China
Published online: 27 Oct 2010.
To cite this article: Wei-Qiang Chen & Gui-Yu Jin (2002) Reactions of [(4-cyano-3-methylsulfanyl-1-phenyl)pyrazol-5-
yl]iminomethylenyl Ethyl Ether with Compounds Containing Amino Group and the Bioactivity of Products, Phosphorus, Sulfur,
and Silicon and the Related Elements, 177:5, 1193-1200, DOI: 10.1080/10426500211705
To link to this article: http://dx.doi.org/10.1080/10426500211705
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1193–1200
C
Copyright 2002 Taylor & Francis
1042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290092488
REACTIONS OF [(4-CYANO-3-METHYLSULFANYL-
1-PHENYL)PYRAZOL-5-YL]IMINOMETHYLENYL
ETHYL ETHER WITH COMPOUNDS CONTAINING
AMINO GROUP AND THE BIOACTIVITY OF
PRODUCTS
Wei-Qiang Chen and Gui-Yu Jin
Institute of Elemento-Organic Chemistry, State Key Laboratory
of Elemento-Organic Chemistry, Nankai University,
Tianjin, China
(Received February 7, 2001; accepted March 24, 2001)
The study on reaction of (1-phenyl-3-methylthio-4-cyanopyrazol-5-yl)-
iminomethylene ethyl ether with compounds containing amino group
was discussed in order to understand its reactivity. Some structures of
compounds were verified by x-ray crystallographic study. The results
of the bioassay showed that some of these compounds showed good
fungicidal activities.
Keywords: Fungicidal activities; iminomethylene ethyl ether; N-
(substituted)pyrazolyl methanimidamine; pyrazolo[3,4-d]pyrimidine;
x-ray crystallography
INTRODUCTION
N-(substituted)phenyl methanimidamines were widely used as agro-
chemicals,1 such as chlorodimeform,2 amitraz.3 In recent years,
heterocycles is a very important consideration in a study on new
pharmaceuticals and agrochemicals.4 Many new agrochemicals con-
taining pyrazole ring have been synthesised, such as fripronil.5 Our
earlier efforts were made to synthesize N-(substituted)pyrazolyl
methanimidamines, the bioassay results showed that this kind of com-
pounds exhibited good fungicidal activities.6 In order to understand
the reactivities of the intermediate, N-[(4-cyano-3-methylsulfanyl-
1-phenyl)pyrazol-5-yl]methylenyl ethyl ether (I), and to broaden
This work was supported by the National Natural Science Foundation of China
(29832050).
Address correspondence to G.-Y. Jin, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300 071, PR China. E-mail: chwqiang@mail.zlnet.com
1193

1194
W.-Q. Chen and G.-Y. Jin
the usage of this kind of compounds, reactions of the intermediate
N-pyrzolymethanimidate with compounds containing amino group
were studied. And the biological activities of some products were
investigated.
DISCUSSION AND RESULTS
1. Reaction of I with Compound Containing
Active Amino Group
In the reaction of I with allylamine, a pyrazolo[3,4-d]pyrimidine prod-
uct IIa was observed. At the beginning of this 0reaction, only product
0
IIa produced. If the reaction time delays, IIa became less and the
main product is IIa. But in the same condition when intermediate re-
acted with ammonium and ethyldiamine, only fused cyclic products
were observed (Scheme 1).
SCHEME 1
Although the dimroth rearrangement occured in reaction of metha-
nimidate with ammonia, hydrazine at room temperature (Scheme 2),7,8
we did not find any 4-(substituted)amino-pyrazolo[3,4-d]pyrimidine
product, but 4-imino-pyrazolo[3,4-d]pyrimidines.
SCHEME 2

Amino Group Bioactivity
1195
2. Reaction of I with Compound Containing Inactive
Amino Group
When N-[(4-cyano-3-methylsulfanyl-1-phenyl)pyrazol-5-yl]methylenyl
ethyl ether I reacted with (substituted)benzoyl hydrazine and phenyl
thiosemicarbazide, the more reactive time was needed. The use of lewis
acid, such as BF3Et2O, can shorten the reaction time. I reacted with
phenyl thiosemicarbazide to give 4-imino-pyrazolo[3,4-d]pyrimidine
product III, but with benzoyl hydrazine to give compounds IId
.
g
At room temperature, I can not react with benzenylhydrazone and
2-nitroiminoimidazolidine without any catalyst. The poor yield of the
products with the catalysis of BF3Et2O may due to most of intermediate
I decomposing into pyrazol-5-ylamine and N-(pyrazol-5-yl)formamide.6
If NaH was added, the reaction occurred to give products in good yield,
although pyrazol-5-ylamine was still observed.
SCHEME 3
3. Spectrum of the Products
The 1H NMR data indicated that the proton of group N CH
in methanimidamine IIa showed double peak and the protons of
group N CH in pyrazolo[3,4-d]pyrimidines showed single peaks. An-
0
other evidence for the difference of the methanimidamine IIa and
pyrazolo[3,4-d]pyrimidine IIa is the C N stretching absorption band
near 2200 cm 1(s).
4. X-ray Crystallography Study of Compound III
In order to comfirm the structure further more, the 4-imino-
pyrazolo[3,4-d]pyrimidine products IIa,9 III were characterized by
x-ray diffraction. The perspective view of compound IIi is showed in

1196
W.-Q. Chen and G.-Y. Jin
FIGURE 1 Perspective view of the compound IIi and the atomic labelling
scheme.
Figure 1 and packing diagram of this compound in a unit cell is shown in
Figure 2. Selected bond distances and angles with their estimated
standard deviations are listed in Table I.
˚
In this compounds, the C(11) N(4) bond distance is 1.312 A, slightly
10
˚
shorter the normal C N bond distance (1.33 A). The plane defined
by C(8), C(9), C(10), N(3), N(4), N(5), C(11), N(6), C(12), N(6), and S(2)
˚
atoms is coplanar within the average deviation of 0.0404 A to form
a fully delocalized system. The six-member ring of C(8), C(9), N(3),
7
6
C(10), N(5), and C(11) atoms formed a
configuration in which the
N(3) atom is sp2 hydrobrid which results in the formation of the trigo-
nal configurations of the N(3) nitrogen. The sum of the C(8)-N(3)-C(11),
C(8)-N(3)-N(2) and C(11)-N(4)-N(2) bond angles is 359.8 . In the unit
cell, there is a weak action between S(2) and S(1) ( x + 1, y + 1,
FIGURE 2 Packing diagram of the compound IIi.

Amino Group Bioactivity
1197
˚
TABLE I Selected Bond Lengths [A] and Angles [ ]
for Compound IIi
C(1)-N(1)
N(1)-C(7)
S(1)-C(7)
N(2)-C(7)
N(2)-N(3)
S(2)-C(12)
S(2)-C(13)
N(3)-C(8)
1.414(4)
1.356(4)
1.716(3)
1.327(4)
1.407(3)
1.736(3)
1.789(3)
1.366(4)
1.368(4)
1.312(4)
124.9(3)
116.5(3)
131.4(3)
112.1(3)
99.96(16)
121.8(3)
119.3(3)
118.7(3)
110.0(2)
131.0(3)
119.0(2)
106.8(2)
115.9(3)
126.9(2)
117.2(2)
125.7(3)
N(6)-C(9)
N(6)-N(7)
N(6)-C(14)
N(7)-C(12)
C(8)-N(5)
N(5)-C(9)
C(9)-C(10)
C(10)-C(11)
C(10)-C(12)
1.355(4)
1.387(3)
1.426(4)
1.311(4)
1.288(4)
1.353(4)
1.384(4)
1.400(4)
1.426(4)
N(3)-C(11)
N(4)-C(11)
C(2)-C(1)-N(1)
C(6)-C(1)-N(1)
C(7)-N(1)-C(1)
C(7)-N(2)-N(3)
C(12)-S(2)-C(13)
C(8)-N(3)-C(11)
C(8)-N(3)-N(2)
C(11)-N(3)-N(2)
C(9)-N(6)-N(7)
C(9)-N(6)-C(14)
N(7)-N(6)-C(14)
C(12)-N(7)-N(6)
N(2)-C(7)-N(1)
N(2)-C(7)-S(1)
N(1)-C(7)-S(1)
N(5)-C(8)-N(3)
C(8)-N(5)-C(9)
N(5)-C(9)-N(6)
N(5)-C(9)-C(10)
N(6)-C(9)-C(10)
C(9)-C(10)-C(11)
C(9)-C(10)-C(12)
114.1(3)
127.4(3)
124.9(3)
107.7(3)
119.0(3)
105.0(3)
C(11)-C(10)-C(12) 135.9(3)
N(4)-C(11)-N(3)
N(4)-C(11)-C(10)
N(3)-C(11)-C(10)
N(7)-C(12)-C(10)
N(7)-C(12)-S(2)
C(10)-C(12)-S(2)
C(19)-C(14)-N(6)
C(15)-C(14)-N(6)
118.2(3)
127.4(3)
114.4(3)
110.5(3)
124.6(2)
124.9(2)
121.8(3)
118.7(3)
˚
z + 1), the distance is 3.436 A. And weak hydrogen bond N(1)—
H(1A) S(1) ( x + 1,
y + 1,
z + 1), N(4)—H(4C) S(1) ( x + 1,
˚
˚
y + 1, z + 1) exist, the distances are 3.575 A and 3.332 A respectively.
5. Biological Activities of Products
The results of bioassay showed that some of the products have good
fungicidal activities. Table II was listed fungical activities of some
products.
EXPERIMENTAL
All melting points were deterimined on Yanco melting point apparatus
and are uncorrected. Element analysis was carried out on an MF-3
automatic analyzer. The 1H NMR spectra were recorded in CDCl3 and
(CD3)2SO resolutions on FX-90Q and AC-P200 spectrometer, and chem-
ical shifts were expressed in units using TMS as internal reference.

1198
W.-Q. Chen and G.-Y. Jin
TABLE II Inhibition Rates of Some Products (%)
Compds.
P. zeaea
A. solania
R. solania
Palob
II
II
II
II
II
23.5
44.7
64.3
29.4
22.6
50.0
58.3
31.6
62.5
/
30.0
68.9
38.5
25.0
/
/
a
a
c
0
90.5
/
/
/
d
g
aIn vitro at the concentration of 50 g/ml.
bIn vivo at the concentration of 500 g/ml.
General Procedure for the Preparation
6
of Compounds IIa,c,h,d
g,I
To a solution of ethyl N-[1-Phenyl-4-cyano)pyrazol-5-yl]formimidate
(0.96 g, 4 mmol) in anhydrous acetonitrile (15 ml) was added phenylth-
iosemicarbazide(0.67 g, 4 mmol) at room temperature. When com-
pounds I disappeared tracing by TLC, the mixture was evaporated.
The residue was purified by silica gel column to give the title
compound (IIi).
General Procedure for the Preparation of Compounds IIb,j
To a solution of 2-nitroiminoimidazolidine (0.52 g, 4 mmol) in anhy-
drous acetonitrile (15 ml), 80% sodium hydride (0.18 g, 6 mmol) was
added. After stirring one-half hour, a solution of ethyl N-[1-Phenyl-
4-cyano)pyrazol-5-yl]formimidate (0.96 g, 4 mmol) in anhydrous ace-
tonitrile (10 ml) was added. When compounds I disappeared tracing
TABLE III Physical Data and Elemental Analysis of Compounds II
Elementary analysis: found (calcd.)
Compd.
Yield (%)
m.p. ( C)
C
H
N
II
II
II
II
II
II
II
II
II
II
II
61.5
28.9
66.4
89.8
74.4
54.8
45.9
58.4
57.3
56.5
89.3
92–94
92–94
60.83(60.58)
60.38(60.58)
60.67(60.62)
55.89(56.01)
60.60(60.62)
59.11(59.10)
59.36(59.10)
51.25(51.25)
57.77(57.76)
55.96(56.00)
48.65(48.64)
4.86(5.08)
5.00(5.08)
4.15(4.28)
4.13(4.31)
4.08(4.28)
4.21(4.46)
4.40(4.46)
3.15(3.17)
4.25(4.47)
4.22(4.20)
4.14(3.81)
23.27(23.55)
23.41(23.55)
22.26(22.32)
27.00(27.22)
22.34(22.32)
20.39(20.68)
20.57(20.68)
18.77(18.87)
25.63(25.91)
23.78(24.00)
29.91(30.25)
a
a
0
218–220
180–181
140–142
186–187
148–150
221–223
258–260
136–137
246–248
b
c
d
e
f
g
h
I
j

Amino Group Bioactivity
1199
TABLE IV 1H NMR Data of Compounds II
Compd.
1H NMR (CDCl3),
II
2.72(s, 3H, CH3S), 4.66 4.74(m, 2H, N CH2), 5.18 5.40(m, 2H, CH2 ),
5.88 6.30(m, 1H, CH ), 7.30 7.58, 7.96 8.08(m, 5H, Ph-H),
7.78(s, 1H, Pyrimidine-H)
2.56(s, 3H, CH3S), 3.94 4.08 (m, 2H, NCH2), 4.72(bs, NH), 5.12 5.36
(m, 2H, C CH2), 5.68 6.10(m, 1H, CH CH2), 7.28 7.50, 7.58 7.84
(m, 5H, Ph-H), 8.36 8.40(d, 1H, N CH)
a
0
II
a
II
II
II
II
II
II
II
2.76(s, 3H, CH3S), 7.02 7.51(m, 9H, Ph-H), 8.06 8.11(d, 2H, N CH),
b
8.46(s, 1H, NH
)
2.74(s, 3H, CH3 S), 6.04 6.30(broad-s, 2H, N H), 7.32 7.68, 8.12 8.34
(m, 5H, Ph-H), 8.46(s, 1H, Pyrimidine-H)
2.60(s, 3H, CH3S), 7.28 8.00(m, 10H, Ph-H), 8.52(s, 1H, CH N),
10.60(broad-s, N H)
2.54(s, 3H, CH3S), 3.68(s, 3H, CH3O), 7.04 7.92(m, 9H, Ph-H),
8.54(s, 1H, CH N), 10.58(broad-s, N H)
2.58(s, 3H, CH3S), 3.84(s, 3H, CH3O), 7.00 7.40, 7.80 8.00(m, 9H,
Ph-H), 8.48(s, 1H, CH N), 10.56(broad-s, N H)
2.78(s, 3H, CH3S), 7.50 8.20(m, 8H, Ph-H), 8.60(s, 1H, CH N),
9.90(broad-s, N H)
2.56(s, 3H, CH3 S), 2.68(s, 3H, CH3 S), 3.64 88(m, 2H, CH2 N),
4.16 4.32(m, 2H, CH2 N), 7.30 8.10(m, 12H, Ph-H, Pyrimidine-H)
2.62(s, 3H, CH3 S), 7.30 7.72(m, 11H, Ph-H, Pyrimidine-H)
2.56(s, 3H, CH3S), 3.66 3.84(m, 4H, CH2CH2 ), 7.32 7.82(m, 5H,
Ph-H), 8.72(s, 1H, N CH)
c
d
e
f
g
h
II
II
i
j
by TLC, the mixture was filtered. The solid was recrystallized from
dimethylformide to give compound IIj.
Physical data and elemental analysis of compounds II are listed in
Table III. Tables IV and V are 1H NMR date and IR data of compounds
II respectively.
TABLE V IR Data of Compounds II
1
IR, /cm
Compd.
N
H
C
N
N
C, C
C
C O
II
II
II
II
II
II
II
II
II
II
II
3296.0
3398.5
3380.5
3437.5
3197.0
3268.5
3243.0
3207.0
3402.0
3420.5
3364.5
/
1634.8
1614.9
1643.6
1655.9
1592.7
1612.6
1592.7
1607.6
1643.9
1647.3
1619.6
1592.6
1500.0
1591.5
1587.8
1502.3
1499.3
1500.9
1497.8
1594.4
1590.5
1592.4
1501.3
1466.7
1510.0
1501.3
1468.6
1479.6
1450.7
1451.6
1502.3
1497.6
1497.0
/
a
a
0
2200.0
/
/
/
/
/
b
c
2214.0
2203.5
2211.5
1659.0
1660.6
1653.2
1657.4
d
e
f
g
/
/
/
/
/
/
h
i
j
2214.5

1200
W.-Q. Chen and G.-Y. Jin
REFERENCES
[1] H. Geissbuhler, K. Kossmann, I. Baunok, et al., J. Argric. Food Chem., 19, 365
(1971).
[2] A.-G. Schering, Ger. Offen. Pat., 1. 172,081; CA61:11274d.
[3] C. Tang, Y. Li, B. Chen, et al., Pesticide Chemistry (Nankai, University Publisher,
1998), p. 211.
[4] W.-Q. Chen, L.-H. Weng, and G.-Y. Jin, Acta. Cryst., E57(1), 1 (2001).
[5] Brighton Crop Protection Conference, Pests and Diseases I, p. 29 (1992).
[6] W.-Q. Chen, J. Ren, F. Yu, et al., Chinese Journal of Pesticide Science (in chinese)
2(2), 15 (2000).
[7] R. S. Hosmane, B. B. Lim, and F. N. Burntt, J. Org. Chem., 53, 382 (1988).
[8] R. S. Hosmane, B. B. Lim, and M. F. Summers, J. Org. Chem., 53, 5309 (1988).
[9] W. Chen, L. Weng, and G. Jin, J. Chem. Crystallogr., 29(12), 1291 (1999).
[10] Y. Sasada, Molecular and Crystal Structures in Chemistry Handbook (The Chemical
Society of Japan, Maruzen, Tokyo, 1984), 3rd ed.