A convenient synthesis and herbicidal activity of N- phosphonoalkylpyrazolo[4,3-e][1,2,4]-triazolo[1,5-d]pyrimidines

Article abstract of DOI:10.1080/10426500802070270

An important building block, diethyl [(5-amino-4-cyano-3-methylsulfanyl- pyrazol-1-yl)-(4-fluorophenyl)methyl] phosphonate (3) was efficiently synthesized via the condensation of 1-hydrazino-1-(4-fluorophenyl)methyl phosphonate (1) with 2-[bis(methylthio)methylene]malononitrile (2).3 reacted with triethyl orthoformate to afford diethyl [(4-cyano-5-ethoxymethyleneamino-3- methylsulfanyl-pyrazol-1-yl)-(4-fluorophenyl)methyl] phosphonate (4), which reacted with various acyl hydrazines in refluxing 2-methoxyethanol to provide the target compounds (5) in good yields directly. The results of preliminary bioassay indicated that compounds 5 possess potent herbicidal activity against the roots of monocotyledonous (barnyard grass) and dicotyledonous (oil rape) plants, and could be further developed as potential herbicides. Copyright Taylor & Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon
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A Convenient Synthesis and
Herbicidal Activity of N-
phosphonoalkylpyrazolo[4,3-
e][1,2,4]-triazolo[1,5-
d]pyrimidines
Lin-Xia Xiao a , Ke Li a & De-Qing Shi a
a Key Laboratory of Pesticide & Chemical Biology of
Ministry of Education, College of Chemistry , Central
China Normal University , Wuhan, 430079, Hubei, P.
R. China
Published online: 03 Nov 2008.
To cite this article: Lin-Xia Xiao , Ke Li & De-Qing Shi (2008) A Convenient Synthesis
and Herbicidal Activity of N-phosphonoalkylpyrazolo[4,3-e][1,2,4]-triazolo[1,5-
d]pyrimidines, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:12,
3156-3165, DOI: 10.1080/10426500802070270
To link to this article: http://dx.doi.org/10.1080/10426500802070270
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Phosphorus, Sulfur, and Silicon, 183:3156–3165, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802070270
A Convenient Synthesis and Herbicidal Activity of
N-phosphonoalkylpyrazolo[4,3-e][1,2,4]-
triazolo[1,5-d]pyrimidines
Lin-Xia Xiao, Ke Li, and De-Qing Shi
Key Laboratory of Pesticide & Chemical Biology of Ministry of
Education, College of Chemistry, Central China Normal University,
Wuhan 430079, Hubei, P. R. China
An important building block, diethyl [(5-amino-4-cyano-3-methylsulfanyl-pyrazol-
1-yl)–(4-fluorophenyl)methyl] phosphonate (3) was efficiently synthesized via the
condensation of 1-hydrazino-1-(4-fluorophenyl)methyl phosphonate (1) with 2-
[bis(methylthio)methylene]malononitrile (2). 3 reacted with triethyl orthoformate
to afford diethyl [(4-cyano-5-ethoxymethyleneamino-3-methylsulfanyl-pyrazol-1-
yl)-(4-fluorophenyl)methyl] phosphonate (4), which reacted with various acyl hy-
drazines in refluxing 2-methoxyethanol to provide the target compounds (5) in good
yields directly. The results of preliminary bioassay indicated that compounds 5
possess potent herbicidal activity against the roots of monocotyledonous (barnyard
grass) and dicotyledonous (oil rape) plants, and could be further developed as po-
tential herbicides.
Keywords 1-Aminoalkyl phosphonate analog; herbicidal activity; pyrazolo[4,3-
e][1,2,4]triazolo[1,5-d]pyrimidine; synthesis
INTRODUCTION
In recent years, 1-aminoalkyl phosphonate analogs, as the phospho-
rus analogs of natural amino acids received an increasing attention
in medicinal chemistry and pesticide science1,2 due to their wide bi-
ological activities such as enzyme inhibitors,3 antibiotics,4 catalytic
antibodies,5 antifungal agents, herbicides, plant growth regulators and
plant virucides.6 Recently, triazolopyrimidines such as Penoxsulam and
Florasulam were commercialized as herbicides7,8; and pyrazolo[4,3-
e]-1,2,4-triazolo-[1,5-d]pyrimidine derivatives such as 8FB-PTP, were
Received 21 February 2008; accepted 20 March 2008.
The project was sponsored by the Natural Science Foundation of china (No. 20302002)
and the Scientific Research Foundation for the Returned Overseas Chinese Scholars,
State Education Ministry (No. [2007] 1108).
Address correspondence to D.-Q. Shi, College of Chemistry, Central China Normal
University, Wuhan 430079, Hubei, P. R. China. E-mail: chshidq@mail.ccnu.edu.cn
3156

N-phosphonoalkylpyrazolo[4,3-e][1,2,4] triazolo[1,5-d]pyrimidines
3157
found to be potent adenosine A2A antagonists.9,10 As part of our ongo-
ing project aimed at investigating novel N-phosphonoalkylheterocycles
with herbicidal activity, we synthesized a series of novel 1-aminoalkyl
phosphonate analogs, N-phosphonoalkylpyrazolo[4,3-e]-1,2,4-triazolo-
[1,5-d]pyrimidines using diethyl [(5-amino-4-cyano-3-methylsulfanyl-
pyrazol-1-yl)-(4-fluorophenyl)methyl] phosphonate as building block.
Herein, we would like to describe the cyclization reaction (Scheme 1)
to synthesize the title compounds 5. The results of bioassay indicated
that 5 possess potent herbicidal activity against the roots of oil rape and
barnyard grass and can be further developed as potential herbicides.
RESULTS AND DISCUSSION
Synthesis
The versatile intermediate, 1-hydrazino-1-(4-fluorophenyl)methyl
phosphonate (1) has been reported by several methods.11 We synthe-
sized it by a modified procedure of Yuan’s report.11a For converting
4-fluoro-benzaldehyde to1-hydroxy-1-(4-fluorophenyl)methyl phospho-
nate, an excess of solid catalyst (KF, four times) caused difficulty in stir-
ring and incomplete reactivity. Instead, we used one molecular catalyst
(Et3N) in CH2Cl2 to avoid these shortcomings and obtained 1-hydroxy-
1-(4-fluorophenyl)methyl phosphonate in a better yield (85%). 1 can be
obtained in a moderate yield (76%) by the reaction of diethyl 1-hydroxyl-
1-(4-fluorophenyl)methyl phosphonate with mesyl chloride, followed by
the nucleophilic substitution with hydrazine in a one-pot reaction.
Cyclization of 1 with 2-[bis(methylthio)methylene]malononitrile (2)
in a mild condition gave diethyl [(5-amino-4-cyano-3-methylsulfanyl-
pyrazol-1-yl)-(4-fluorophenyl)methyl] phosphonate (3), which could
easily convert to the corresponding imidate (4) (89%) in refluxing tri-
ethyl orthoformate. 4 reacted with various acyl hydrazines to yield
the corresponding tricyclic target compounds 5a∼5h conveniently in
refluxing 2-methoxyethanol in one step (Scheme 1), without the iso-
lation of 5-acylamino-4-imino-4,5-dihydropyrazolo[3, 4-d]pyrimidines,

3158
L.-X. Xiao et al.
SCHEME 1 Synthetic route of title compounds 5.
FIGURE 1 X-ray crystal structure of unfluorinated analog 5.
opposite to the report by Baraldi et al.12 In Baraldi’s report, anal-
ogous imidates reacted with various acyl hydrazines in refluxing 2-
methoxyethanol to give 5-acylamino-4-imino-4,5-dihydropyrazolo[3, 4-
d]pyrimidines. While the ring closure to the corresponding pyrazolo[4,3-
e]-1,2,4-triazolo-[1,5-d]pyrimidines thermally needed a higher boiling
point solvent (260◦C) like diphenyl ether.
The structures of compounds 5a∼5h were deduced from their spec-
1
tra data (IR, H NMR, 31P NMR, MS and elemental analyses). One of
its unfluorinated analogs was determined by X-ray diffraction crystal-
lography as an example (Figure 1). For more detail information, please
see Xiao and Shi.13

N-phosphonoalkylpyrazolo[4,3-e][1,2,4] triazolo[1,5-d]pyrimidines
3159
Biological Activities
The herbicidal activity of title compounds 5 against Brassica napus
(rape) and Echinochloa crus-galli (barnyard grass) has been investi-
gated at the dosages of 100 mg/L and 10 mg/L compared with distilled
water and the commercially available herbicide, 2,4-dichlorophenoxy
acetic acid (2,4-D) according to the method described in the experimen-
tal section. The preliminary results of bioassay showed that some of
compounds 5 possess potent and selective herbicidal activities against
dicotyledonous weeds such as oil rape at the dosage of 100 mg/L. Com-
pounds 5 not only show stronger inhibitory activity against oil rape
than barnyard, but also those roots than stalks. The herbicidal activity
decreases with the decrease of the dosage of compounds 5. From Table
I, we noticed that the substituent R had some effect on the herbici-
dal activity. For example, the 2,4-dichlorophenoxymethyl substituted
compound have the best activity, while the 4-(t-butyl)-phenoxymethyl
substituted one have the lowest activity. Moreover, compounds con-
taining halogen atoms in R group have better activities than that of no
halogen ones. The QSAR studies of 5 are under investigation.
EXPERIMENTAL
Melting points were determined with a WRS-1B digital melting point
apparatus and are uncorrected. 1H and 31P NMR spectra were recorded
on Varian MERCURY-PLUS400 (400 MHz) spectrometer with CDCl3
as the solvent and TMS and 85% H3PO4 as the internal and external
TABLE I The Herbicidal Activity of Compounds 5 (inhibitory rate%)
Relative inhibition (root%/stalk%)
Rape
Barnyard grass
Compd.
R
100 mg/L 10 mg/L 100 mg/L 10 mg/L
5a
5b
5c
5d
5e
5f
4-totyl
4-methoxyphenyl
phenoxymethyl
51.1/29.2 25.0/29.2 75.7/40.0 18.9/17.1
85.2/50.0 33.4/8.3 59.5/17.1 29.7/17.1
85.5/57.9 48.7/35.2 79.4/42.1 34.3/28.6
82.4/45.8 54.3/42.1 79.4/60.0 42.9/28.0
79.5/58.3 29.5/41.7 81.1/51.4 48.6/22.9
96.8/73.6 53.2/47.0 88.2/57.1 58.8/28.6
51.0/42.7 37.5/30.8 47.6/32.5 42.8/29.0
4-chlorophenoxymethyl
3-chlorophenoxymethyl
2,4-dichlorophenoxymethyl
4-(t-butyl)phenoxymethyl
5g
5h
2,4-D
3-(trifluoromethyl)phenoxymethyl 70.5/66.7 27.3/41.7 86.5/45.7 78.4/45.7
99.0/91.5 98.2/91.2 97.5/33.5 97.5/31.2

3160
L.-X. Xiao et al.
references, respectively. Mass spectra were obtained with a Finnigan
TRACEMS2000 spectrometer using the EI method; IR spectra were
measured by a Nicolet NEXUS470 spectrometer; Elemental analyses
were performed with an Elementar Vario EL III CHNSO elementary
analyzer. All of the solvents and materials were reagent grade and
purified as required. 1-Hydrazino-1-(4-fluorophenyl)methyl phospho-
nate (1),11a 2-[bis(methylthio)methylene]malononitrile (2),14 and acyl
hydrazines,15 were prepared according to the literature procedures.
Preparation of Diethyl [(5-Amino-4-cyano-3-methylsulfanyl-
pyrazol-1-yl)-(4-fluorophenyl)methyl] Phosphonate (3) 16
A mixture of 1 (6.71 g, 24.3 mmol), 2 (3.89 g, 22.9 mmol) and ethanol (30
mL) was refluxed for 5 h. After cooling, the reaction mixture was con-
centrated in vacuo and recrystallized from ethyl acetate and petroleum
(1:1, v/v) to give white crystals (6.50 g, 71% yield). m.p. 158–159◦C.
1H NMR (CDCl3,400 MHz)δ: 1.19–1.27 (m, 6H, 2CH3), 2.53 (s, 3H,
SCH3), 4.01–4.16 (m, 4H, 2CH2), 5.56 (s, 2H, NH2), 5.72 (d,J = 24 Hz,
1H, PCH), 7.28–7.50 (m, 4H, Ar-H); anal. calcd. for C16H20FN4O3PS: C
48.24, H 5.06, N 14.06; found C 48.39, H 4.81, N 14.14.
Preparation of Diethyl [(4-Cyano-5-ethoxymethyleneamino-3-
methylsulfanyl-pyrazol-1-yl)- (4-fluorophenyl)-methyl]
Phosphonate (4)
5-Amino-4-cyano-pyrazole 3 (2.39 g, 6 mmol) were dissolved in triethyl
orthoformate (4 mL), and the mixture was refluxed for 2 h. After cooling,
the solvent was removed under a reduced pressure, and the residue was
purified on silica gel (EtOAc-light petroleum ether, 1:5, v/v) to afford 4
as a white solid (2.42 g, 89%). m.p. 77–78◦C. 1H NMR (CDCl3, 400 MHz)
δ 1.19–1.31 (m, 6H, 2CH3), 1.42 (t, J = 7.2 Hz, 3H, CH3), 2.61 (s, 3H,
SCH3), 4.02–4.05 (m, 2H, CH2), 4.14–4.18 (m, 2H, CH2), 4.38–4.41 (m,
2H, CH2), 5.87 (d,J = 22.4 Hz, 1H, PCH), 7.04 (t, J = 8.4 Hz, 2H, Ar-H),
7.54 (q, J = 5.2 Hz, J = 8.4 Hz, 2H, Ar-H), 8.41 (s, 1H, N=CH); anal.
calcd. for C19H24FN4O4PS: C 50.21, H 5.32, N 12.33; found C 50.03, H
5.15, N 12.18.

N-phosphonoalkylpyrazolo[4,3-e][1,2,4] triazolo[1,5-d]pyrimidines
3161
Preparation of Diethyl
{2-Substituted-9-(methylsulfanyl)-7H-
pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-
yl}substitutedphenylmethyl Phosphonate (5)—General
Procedure
A solution of 4 (0.65 g. 1.5 mmol) and acyl hydrazine (1 mmol) in
methoxyethanol (20 mL) was stirred under reflux for 3–5 h. After cool-
ing, the solvent was removed under reduced pressure, and the residue
was purified on silica gel (acetone and light petroleum,1:6, v/v) to yield
the corresponding target compound 5a–5h.
Diethyl [2-(4-totyl)-9-(methylsulfanyl)-7H-pyrazolo-[4,3-e]-
1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-fluorophenyl)methyl
Phosphonate (5a)
Colorless crystals: yield 73%; m.p. 145.6–146.7◦C; 1H NMR (CDCl3,
400 MHz) δ: 1.18 (t, J = 7.6 Hz, 3H, CH3), 1.26 (t, J = 7.6 Hz, 3H,
CH3), 2.43 (s, 3H, CH3), 2.87 (s, 3H, SCH3), 4.02–4.10 (m, 2H, CH2O),
4.18–4.22 (m, 2H, CH2O), 6.42 (d,J = 23 Hz, 1H, PCH), 7.06 (t, J = 8.4
Hz, 2H, Ar-H), 7.31 (t, J = 8.4 Hz, 2H, Ar-H), 7.74 (q, J = 5.2 Hz, J =
7.2 Hz, 2H, Ar-H), 8.23 (d, J = 8.0 Hz, 2H, Ar-H), 9.08 (s, 1H, N=CH);
31P NMR (CDCl3, 162 MHz) δ: 15.71; IR(KBr) (cm−1): 2984 (Ar-H), 1452
(Ar-H), 1257 (P=O), 1022 (P-O-C), 752(P-C); EIMS (probe) 70eV, m/z
(rel. int.): 542 (23), 540 (100) [M]+, 405 (11), 403 (75.5), 357 (6.4), 109
(11.2); anal. calcd. for C25H26FN6O3PS: C 55.55, H 4.85, N 15.55; found
C 55.71, H 5.00, N 15.37.
Diethyl [2-(4-Methoxyphenyl)-9-(methylsulfanyl)-7H-pyrazolo-
[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-fluorophenyl)-
methyl Phosphonate (5b)
1
Colorless crystals: yield 85%; m.p. 164.3-165.2oC; H NMR (CDCl3,
400 MHz) δ: 1.18 (t, J = 7.2 Hz, 3H, CH3), 1.25 (t, J = 7.2 Hz, 3H,
CH3), 2.86 (s, 3H, SCH3), 3.89 (s, 3H, OCH3), 4.02–4.09 (m, 2H, CH2O),
4.18–4.21 (m, 2H, CH2O), 6.42 (d,J = 22.8 Hz, 1H, PCH), 7.01–7.08
(m, 4H, Ar-H), 7.74 (q, J = 5.2 Hz, J = 7.2 Hz, 2H, Ar-H), 8.28 (d, J =
8.8 Hz, 2H, Ar-H), 9.06 (s, 1H, N=CH); 31P NMR (CDCl3, 162 MHz)
δ: 15.78; IR(KBr) (cm−1): 2978 (Ar-H), 1487, 1242 (P=O), 1026(P-O-C),
748 (P-C); anal. calcd. for C25H26FN6O4PS: C 53.95, H 4.71, N 15.10;
found C 53.64, H 4.61, N 14.97.

3162
L.-X. Xiao et al.
Diethyl[2-(Phenoxymethyl)-9-(methylsulfanyl)-7H-pyrazolo-
[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-fluoro-
phenyl)methyl Phosphonate (5c)
Colorless crystals: yield 79%; m.p. 124.0–124.7oC; 1H NMR (CDCl3,
400 MHz) δ: 1.19 (t, J = 7.2 Hz, 3H, CH3), 1.26 (t, J = 7.2 Hz, 3H,
CH3), 2.82 (s, 3H, SCH3), 4.01–4.08 (m, 2H, CH2O), 4.10–4.20 (m, 2H,
CH2O), 5.42 (s, 2H, CH2O), 6.45 (d,J = 22.8 Hz, 1H, PCH), 6.97–7.06
(m, 5H, Ar-H), 7.24–7.32 (m, 2H, Ar-H), 7.73 (s, 2H, Ar-H), 9.08 (s, 1H,
N=CH); 31P NMR (CDCl3, 162 MHz) δ: 15.52; IR(KBr) (cm−1): 2990
(Ar-H), 1252 (P=O), 1030 (P-O-C), 758 (P-C); EIMS (probe) 70eV, m/z
(rel. int.): 556 [M]+ (18), 419 (100), 326 (16), 279 (12), 109 (11); anal.
calcd. for C25H26FN6O4PS: C 53.95, H 4.71, N 15.10; found C 54.13, H
4.54, N 14.88.
Diethyl [2-(4-Chlorophenoxymethyl)-9-(methylsulfanyl)-7H-
pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-fluoro-
phenyl)methyl Phosphonate (5d)
Colorless crystals: yield 81%; m.p. 127.7–129.0oC; 1H NMR (CDCl3,
400 MHz) δ: 1.19 (t, J = 7.2 Hz, 3H, CH3), 1.26 (t, J = 7.2 Hz, 3H, CH3),
2.82 (s, 3H, SCH3), 4.02–4.09 (m, 2H, CH2O), 4.17–4.21 (m, 2H, CH2O),
5.38 (s, 2H, CH2O), 6.41 (d,J = 22.8 Hz, 1H, PCH), 6.98 (d, J = 8.8 Hz,
2H, Ar-H), 7.06 (t, J = 8.8 Hz, 2H, Ar-H), 7.25 (t, J = 7.6 Hz, 2H, Ar-H),
7.74 (q, J = 5.2 Hz, J = 7.2 Hz, 2H, Ar-H), 9.07 (s, 1H, N=CH); 31P
NMR (CDCl3, 162 MHz) δ: 15.91; IR (KBr) (cm−1): 2985 (Ar-H), 1502
(Ar-H), 1246 (P=O), 1026 (P-O-C), 748 (P-C); EIMS (probe) 70eV, m/z
(rel. int.): 590 [M]+ (19), 453 (100), 326 (16), 280 (22), 109 (20); anal.
calcd. for C25H25ClFN6O4PS: C 50.81, H 4.26, N 14.22; found C 51.05,
H 4.07, N 14.43.
Diethyl [2-(3-Chlorophenoxymethyl)-9-(methylsulfanyl)-7H-
pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-
fluorophenyl)methyl Phosphonate
(5e)
Colorless crystals: yield 76%; m.p. 112.1–113.5oC; 1H NMR (CDCl3,
400 MHz) δ: 1.19 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H,
CH3), 2.81 (s, 3H, SCH3), 4.04–4.07 (m, 2H, CH2O), 4.17–4.21 (m, 2H,
CH2O), 5.39 (s, 2H, CH2O), 6.41 (d,J = 22.4 Hz, 1H, PCH), 6.93–6.98
(m, 2H, Ar-H), 7.03–7.07 (m, 3H, Ar-H), 7.21 (t, J = 8.4 Hz, 1H, Ar-H),
7.72 (q, J = 5.2 Hz, J = 7.6 Hz, 2H, Ar-H), 9.07 (s, 1H, N=CH); 31P
NMR (CDCl3, 162 MHz) δ: 15.86; IR (KBr) (cm−1): 2978 (Ar-H), 1649,
1593, 1480, 1457 (Ar-H), 1266, 1228 (P=O), 1163, 1059 (P-O-C), 773
(P-C); EIMS (probe) 70eV, m/z (rel. int.): 593 (6.0), 592 (8.0), 590 (23.9)

N-phosphonoalkylpyrazolo[4,3-e][1,2,4] triazolo[1,5-d]pyrimidines
3163
[M]+, 542 (19.4), 540 (100), 456 (21.2), 453 (85.5), 405 (8.5), 404 (52.7),
357(7.0), 109 (19.5); anal. calcd. for C25H25ClFN6O4PS: C 50.81, H 4.26,
N 14.22; found C 51.10, H 4.37, N 14.32.
Diethyl [2-(2,4-Dichlorophenoxymethyl)-9-(methylsulfanyl)-7H-
pyrazolo-[4,3-e]-
1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-fluorophenyl)methyl
Phosphonate (5f)
Colorless crystals: yield 88%; m.p. 155.2–157.0◦C; 1H NMR (CDCl3,
400 MHz) δ: 1.19 (t, J = 6.8 Hz, 3H, CH3), 1.26 (t, J = 6.8 Hz, 3H,
CH3), 2.82 (s, 3H, SCH3), 4.04–4.07 (m, 2H, CH2O), 4.18–4.21 (m, 2H,
CH2O), 5.45 (s, 2H, CH2O), 6.41 (d,J = 22.4 Hz, 1H, PCH), 7.02–7.08
(m, 3H, Ar-H), 7.16 (d, J = 6.4 Hz, 1H, Ar-H), 7.38 (s, 1H, Ar-H), 7.73
(q, J = 5.2 Hz, J = 7.2 Hz, 2H, Ar-H), 9.07 (s, 1H, N=CH); 31P NMR
(CDCl3, 162 MHz) δ: 16.05; IR (KBr) (cm−1): 2984 (Ar-H), 1252 (P=O),
1024 (P-O-C), 756 (P-C); anal. calcd. for C25H24Cl2FN6O4PS: C 48.01,
H 3.87, N 13.44; found C 47.86, H 3.95, N 13.27.
Diethyl [2-(4-T-butyl phenoxymethyl)-9-(methylsulfanyl)-
7H-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-d]-pyrimidin-7-yl]-(4-
fluorophenyl)methyl Phosphonate
(5g)
Colorless crystals: yield 70%; m.p. 104.1–105.6◦C; 1H NMR (CDCl3,
400 MHz) δ: 1.19 (t, J = 7.2 Hz, 3H, CH3), 1.25 (t, J = 7.2 Hz, 3H, CH3),
1.31 (s, 9H, CH3), 2.82 (s, 3H, SCH3), 3.98–4.16 (m, 2H, CH2O), 4.18–
4.21 (m, 2H, CH2O), 5.40 (s, 2H, CH2O), 6.42 (d,J = 22.4 Hz, 1H, PCH),
6.98–7.08 (m, 4H, Ar-H), 7.31 (d, J = 6.8 Hz, 2H, Ar-H), 7.73 (q, J = 5.6
Hz, J = 8.0 Hz, 2H, Ar-H), 9.08 (s, 1H, N=CH); 31P NMR (CDCl3, 162
MHz) δ: 15.47; IR(KBr) (cm−1): 2985 (Ar-H), 1248 (P=O), 1028 (P-O-C),
746 (P-C); EIMS (probe) 70eV, m/z (rel. int.): 614 (9.3), 612 (25.7) [M]+,
475 (100), 459 (6.1), 419 (18.6), 326 (21.4), 279 (13.8), 109 (7.9); anal.
calcd. for C29H33ClFN6O4PS: C 53.83, H 5.14, N 12.99; found C 54.08,
H 5.40, N 12.73.
Diethyl [2-(3-Trifluoromethylphenoxymethyl)-9-(methyl-
sulfanyl)-7H-pyrazolo-[4,3-e]- 1,2,4-triazolo-[1,5-d]-pyri-
midin-7-yl]-(4-fluorophenyl)methyl Phosphonate (5h)
1
Colorless crystals: yield 71%; m.p. 38–39◦C; H NMR (CDCl3, 400
MHz) δ: 1.19 (t, J = 7.2 Hz, 3H, CH3), 1.28 (t, J = 7.2 Hz, 3H, CH3),
2.82 (s, 3H, SCH3), 4.04–4.09 (m, 2H, CH2O), 4.17–4.21 (m, 2H, CH2O),
5.45 (s, 2H, CH2O), 6.41 (d,J = 22.8 Hz, 1H, PCH), 7.06 (t, J = 8.4
Hz, 2H, Ar-H), 7.22 (d, J = 8.8 Hz, 2H, Ar-H), 7.33 (s, 1H, Ar-H), 7.39

3164
L.-X. Xiao et al.
(t, J = 8.4 Hz, 1H, Ar-H), 7.73 (q, J = 5.6 Hz, J = 7.0 Hz, 2H, Ar-H),
9.07 (s, 1H, N=CH); 31P NMR (CDCl3, 162 MHz) δ: 16.18; IR (KBr)
(cm−1): 2992 (Ar-H), 1245 (P=O), 1026 (P-O-C), 758 (P-C), 694, 565;
EIMS (probe) 70eV, m/z (rel. int.): 624 [M]+ (17), 487 (100), 326 (17),
280 (21), 109 (21); anal. calcd. for C26H24ClF4N6O4PS: C 47.39, H 3.67,
N 12.75; found C 47.27, H 3.62, N 12.95.
Herbicidal Activities Testing
Herbicidal testing of the newly synthesized compounds 5 was carried
out in a greenhouse, with temperature 23
(RH) 60 5%, light intensity 10 Klux, photoperiod 8 h/day. Twenty
1◦C, relative humidity
seeds of each weed species including oil rape and barnyard grass were
chosen for testing. Seedlings were grown in a 9-cm diameter test plate
containing two pieces of filter paper, and 9 mL solution of the tested
compound (100 mg/L and 10 mg/L, respectively). Distilled water and
2,4-D were used as the comparison compounds. The herbicidal activity
was assessed as the inhibitory rate in comparison with the distilled
water. The herbicidal rating score based on visual observation. Range
from 0% to 100%, 0% means no effect, 100% means complete killing.
The test was run three times, and the results were averaged and given
as activity in Table I.
CONCLUSIONS
In conclusion, we have developed an efficient and selective synthesis of
N-phosphonoalkylpyrazolo[4,3-e]-1,2,4-triazolo-[1,5-d]pyrimidines, via
the direct ring closure of functionalized imidates with various acyl
hydrazines. The preliminary biological evaluation showed that these
compounds have potent and selective herbicidal activity.
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