Synthesis and biological actvities of o, o-dialkyl-dithiophosphoryl-s-acetoxy triazolo compounds

Article abstract of DOI:10.1080/10426500307939

In this article, we introduce organic phosphorus moiety into triazole ring to prepare O-dialkyl-dithiophosphoryl-S-acetoxy triazolo compounds and characterize their structures by elementary analysis and ¹HNMR and IR spectral data. From the resu

Full text of DOI:10.1080/10426500307939

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis and Biological Activities of O, O-Dialkyl-
dithiophosphoryl-S-acetoxy Triazolo Compounds
Wen-Bin Chen a & Gui-Yu Jin a
a Nankai University , Tianjin, China
Published online: 27 Oct 2010.
To cite this article: Wen-Bin Chen & Gui-Yu Jin (2003) Synthesis and Biological Activities of O, O-Dialkyl-dithiophosphoryl-
S-acetoxy Triazolo Compounds, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:2, 311-317, DOI:
10.1080/10426500307939
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:311–317
C
Copyright 2003 Taylor & Francis
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DOI: 10.1080/10426500390170435
SYNTHESIS AND BIOLOGICAL ACTIVITIES
OF O, O-DIALKYL-DITHIOPHOSPHORYL-S-ACETOXY
TRIAZOLO COMPOUNDS
Wen-Bin Chen and Gui-Yu Jin
Nankai University, Tianjin, China
(Received May 10, 2002; accepted June 9, 2002)
In this article, we introduce organic phosphorus moiety into tria-
zole ring to prepare O-dialkyl-dithiophosphoryl-S-acetoxy triazolo com-
pounds and characterize their structures by elementary analysis and
1HNMR and IR spectral data. From the results of biological activity
screening, we found that the O-dialkyl-dithiophosphoryl-S-acetoxy tri-
azolo compounds show lower fungicidal activities and their structures
need to be optimized for the better.
Keywords: Biological activities; organic phosphorus; synthesis; triazole
INTRODUCTION
Organic phosphorus compounds are biologically versatile as they are
pesticides, fungicides, and herbicides,1–4 and many compounds have
been commercialized. At the same time, triazole compounds also pos-
sess pesticidal, herbicidal, and fungicidal activities and plant growth
regulation activities.5–11 The introduction of organic phosphorus in tri-
azole compounds not only reduces the toxicity of organic phosphorus
compounds on mammalian, but also expands the application scope of
triazole compounds. However, triazole compounds containing organic
phosphorus are seldom reported.12,13 To study the biological activities
of all kinds of triazole compounds, we incorporated organic phosphorus
moiety in triazole compounds to prepare O-dialkyl-dithiophosphoryl-
S-acetoxy triazolo compounds. The syntheses of these compounds are
outlined in Schemes 1, 2, and 3.
The authors wish to thank the National Natural Science Foundation of China
(No. 29832050) for support of this project.
Address correspondence to Gui-Yu Jin, Institute of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, People’s Republic of China. E-mail: wbchen@
eyou.com
311

312
W.-B. Chen and G.-Y. Jin
SCHEME 1
SCHEME 2
SCHEME 3
RESULTS AND DISCUSSION
Preparation of O-Dialkyl-dithiophosphoryl-S-acetoxy
Triazolo Compounds (5)
During the course of our experiment, we found that the intermediate 3
was unstable and decomposed for some time to a unknown solid. Thus,
compounds 3 must be freshly prepared before using.
The base is necessary to this reaction. Results show that no product
was obtained when the base was absent. At the same time, we tested
such bases as triethylamine, pyridine, and potassium carbonate. Here,
the reactant became very complex and no obvious product was detected
using potassium carbonate as a base. When we used pyridine as a base,
the same result was observed. Only using triethylamine, were we able to
obtain the desired result. On the other hand, the reaction temperature
is an important factor in the reaction. A higher temperature lead to
dark color and complicated unknown compounds; at room temperature
or a lower temperature, desired results were observed. In the end, we
found that the intermediate 3b is more reactive than 3a, as it reacts at
lower temperature.

Synthesis and Biological Activities of Triazolo Compounds
313
TABLE I The IR Data of Compounds 5
IR (v/cm 1, film)
Compd.
C
O
C
N (triazole)
C
H (triazole)
P
S
P O C
5a
5b
5c
5d
5e
5f
1727.7, 1751.3 1505.9, 1476.9
1726.3, 1751.8 1504.9, 1475.3
1723.5, 1754.4 1503.0, 1467.3
1723.8, 1758.4 1503.4, 1478.9
1704.6, 1758.1 1507.0, 1440.4
1704.7, 1756.1 1506.8, 1459.3
1707.8, 1752.8 1506.9, 1461.8
3102.5
3109.0
3108.0
3112.0
3108.5
3103.5
3100.0
654.1 1009.4, 1173.7, 771.2
668.3 1000.4, 1180.1, 793.0
658.5 993.4, 1180.5, 757.6
653.1 994.7, 1182.5, 749.4
654.2 1006.1, 1153.9, 783.7
656.8 977.4, 1154.2, 747.6
649.2 995.6, 1154.6, 771.3
5g
Characterizations of O-Dialkyl-dithiophosphoryl-
S-acetoxy Triazolo Compounds
The IR spectrum of the O-dialkyl-dithiophosphoryl-S-acetoxy triazolo
1
compounds exhibited two sharp bands around 1700 1750 cm due
1
to the two C O functions, whereas the bands around 650 cm and
1
1000 cm were attributed to P S and P O C groups respectively.
The other data was outlined in Table I.
With respect to the 1HNMR spectra, there is much difference because
of the different substituents R and R0. When R is i-Pr, the two i-propoxy
bonded to phosphorus atom are not equal to appear two doublet peaks.
But the difference is so small that triplet peaks were observed. While
R is Me, Et, and n-Pr, the two alkyoxy groups are equal and the same
chemical shifts were observed. At the same time, different substituent
R0 also affect the chemical shift of the methenyl group bonded to triazole
ring. When R0 is i-butyl, it appeared as singlet peak at 7.3, while R0 is
4-FC6H4, the singlet peak was observed at 8.5–8.7. The detailed data
was shown in Table II.
Biological Activities Results
We selected some compounds 5 to test their fungicidal and insectici-
dal activities and found that they possess some fungicidal but no in-
sectididal activities. Some results of these compounds are outlined in
Table III.
EXPERIMENTAL
1HNMR spectra were recorded in CDCl3 as solvent on an AC-P200 in-
strument using TMS as an internal standard. IR spectra were measured

314
W.-B. Chen and G.-Y. Jin
TABLE II The IR Data of Compounds 5
Compd.
1HNMR (ppm), JP H(Hz) (CDCl3 /TMS)
5a
1.15 (s, 9H, 3 CH3), 3.73 (d, 2H, CH2S, JP =15.33), 3.78 (d, 6H, 2 CH3O,
H
JP =15.22), 7.36 (s, 1H, CH), 8.05 (s, 1H, Tr-H), 8.51 (s, 1H, Tr-H)
H
5b
5c
5d
5e
5f
1.13 (s, 9H, 3 CH3), 1.29 (t, 6H, 2 CH3CH2O), 3.73 (d, 2H, CH2S,
JP =17.77), 4.15 (m, 4H, 2 CH3CH2O, JP =15.22), 7.31 (s, 1H, CH),
H
H
8.00 (s, 1H,Tr-H), 8.36 (s, 1H, Tr-H)
0.96 (t, 6H, 2 CH3CH2CH2O), 1.18 (s, 9H, 3 CH3), 1.72 (m, 4H,
2
2
CH3CH2CH2O), 3.79 (d, 2H, CH2S, JP =17.73), 3.98 (m, 4H,
H
CH3CH2CH2O), 7.38 (s, 1H, CH), 8.08 (s, 1H, Tr-H), 8.55 (s, 1H, Tr-H)
1.19 (s, 9H, 3 CH3), 1.34 (t, 12H, 2 (CH3)2CH), 3.82 (d, 2H, CH2S,
JP =17.39), 4.81 (m, 2H, 2 (CH3)2CH), 7.39 (s, 1H, CH), 8.09 (s, 1H,
H
Tr-H), 8.52 (s, 1H, Tr-H)
1.33 (t, 6H, 2 CH3CH2O), 3.80 (d, 2H, CH2S, JP
=18.34), 4.13 (m, 4H,
H
2
CH3CH2O), 7.12 7.22, 7.91 7.98 (m, 4H, C6H4), 7.82 (s, 1H, Tr-H),
8.05 (s, 1H, Tr-H), 8.56 (s, 1H, CH)
0.95 (t, 6H, 2 CH3CH2CH2O), 1.71 (m, 4H, 2 CH3CH2 CH2O), 3.81
(d, 2H, CH2S, JP =17.87), 4.06 (m, 4H, 2 CH3CH2CH2O), 7.13 7.22,
H
7.91 8.02 (m, 4H, C6H4), 7.84 (s, 1H, Tr-H), 8.07 (s, 1H, Tr-H), 8.71
(s, 1H, CH)
5g
1.31 (t, 12H, 2 (CH3)2CHO), 3.83 (d, 2H, CH2S, JP =17.54), 4.81 (m, 2H,
H
2
(CH3)2CHO), 7.12 7.23, 7.93 8.01 (m, 4H, C6H4), 7.85 (s, 1H, Tr-H),
8.07 (s, 1H, Tr-H), 8.68 (s, 1H, CH)
on a Nicolet 5DX IR spectrometer. Elemental analyses were conducted
on an MF-3 automatic analyzer. Melting points were determined on
an MP-500 melting point apparatus. Refractive indices were obtained
by use of Abbe refractometer. All temperatures and pressures are
uncorrected.
TABLE III The Fungicidal Activities of Compounds 5
Fungicidal activities (%)
In vivo (500 ppm)
In vitro (50 ppm)
S.
P.
B.
A.
P.
P.
G.
C.
Compd. sclerotiorum recibduta cinerea solani asparagi piricola zeae arachidicola
5a
5b
5c
5d
5e
5
0
10
0
0
0
10
10
0
0
0
0
0
49.6
4.8
9.5
0
0
9.5
0
10
0
0
0
7.7
11.5
3.8
11.5
7.7
2.8
2.8
5.6
2.8
5.6
0
0
0
6.7
6.7
15

Synthesis and Biological Activities of Triazolo Compounds
315
TABLE IV Some Data of Compounds of 1 and 2
Compd.
R
m.p. ( C)
Yield (%)
Compd.
R
n2D5
Yield (%)
1a
1b
1c
1d
Me
Et
n-Pr
i-Pr
190
213
168 70
204
2
4
52.3
48.7
44.1
40.2
2a
2b
2c
2d
Me
Et
n-Pr
i-Pr
1.5070
1.5078
1.5056
1.5046
98.0
96.0
86.9
97.1
6
Preparations of Intermediates
Preparation of O,O-Dialkylphosphinothioylthioacetic
Acetic Acid 214,15
According to the literature procedure, potassium O,O-diethyl-
phosphorodithioate14 was treated with chloracetic acid in acetone to
give the liquid that was purified by silicon gel column chromatography
using petroleum ether as eluent to give the compound 2b, yield 96.0%,
25
nD 1.5078, 1HNMR ( /ppm, CDCl3): 134 (t, 6H, 2 CH3CH2O), 3.67
(d, 2H, CH2S JP =17.54 Hz), 4.11–4.23 (m, 4H, 2
CH3CH2O),
H
9.98(brs, 1H, COOH).
Similarly, other compounds 2 were prepared from the correspond-
ing potassium, and some data of compounds 1 and 2 were shown in
Table IV.
Preparations of Bromo Ketone 416
Triazolo ketone 3 was treated with bromine in acetic acid and sodium
acetate anhydride to give the crude products 4a and 4b which not pu-
rified for the next step, yield 84.4% and 95.4%.
Preparations of O-Dialkyl-dithiophosphoryl-S-acetoxy
Triazolo Compounds 5
To the mixture of O, O-dimethylphosphinothioylthioacetic acetic acid
2a 1.08 g (5.0 mmol), and 30 mL of dry acetone, was added 0.56 g
(5.5 mmol) Et3N by stirring at room temperature. After addition, the
mixture was cooled to 0 5 C with ice-water bath, 1.23 g (5.0 mmol) 3,
3-dimethyl-1-bromo-1-(1H-1, 2, 4-triazolo-1-yl)-2-butanone 3a in 5 mL
of dry acetone was added to the reactant, then triethylamine hydrobro-
mide appeared. After the addition was completed, the ice-water bath
was removed and the mixture was stirred for 4 h at room temperature.
The solvent was evaporated off under reduced pressure, and the residue
was diluted with 30 mL of CH2Cl2 and washed with water and dried
over MgSO4. After removal of solvent, the residue was separated by
silicon gel chromatography using ethyl acetate/petroleum ether as elu-
ent to give the viscous liquid, 1.54 g, yield 80.8%. The other compounds
5b–5d were prepared by the same procedure.

316
W.-B. Chen and G.-Y. Jin
TABLE V The Data of Compounds 5
Elementary analyses (% calcd.)
Yield
(%)
Compd.
R
R0
m.p. ( C)
C
H
N
5a
Me
(CH3)3C
Viscous liquid
80.8
80.2
65.6
62.5
77.8
61.3
59.5
37.80
(37.79)
41.10
(41.08)
43.67
(43.94)
43.98
(43.94)
43.04
(42.95)
45.08
(45.47)
45.64
5.09
(5.25)
5.62
(5.87)
6.19
(6.41)
6.16
(6.41)
3.99
(4.25)
4.71
(4.84)
4.47
10.89
(11.02)
10.17
(10.27)
9.34
(9.61)
9.33
(9.61)
8.87
(9.39)
8.68
(8.84)
8.40
5b
5c
5d
5e
5f
Et
n-Pr
i-Pr
Et
(CH3)3C
(CH3)3C
(CH3)3C
4-FC6H4
Viscous liquid
Viscous liquid
46 48
Viscous liquid
Viscous liquid
Viscous liquid
n-Pr 4-FC6H4
i-Pr 4-FC6H4
5g
(45.47)
(4.84)
(8.84)
Similarly, to the mixture of 1.22 g (5.0 mmol) O, O-diethyl-
phosphinothioylthioacetic acetic acid 2b, 0.56 g (5.5 mmol) Et3N, and
30 mL of acetone, was added 1.42 g (5.0 mmol) -(1H-1,2,4-triazolo-1-
yl)- -bromo-para-fluoroacetonphenone 3b in 5 mL of acetone at 0 5 C.
After the addition, the mixture was stirred for 2 h under this condi-
tion. Then the reactant was poured into 50 mL of ice-water, extracted
with 3 20 mL of chloroform, washed with water twice, and dried over
MgSO4. After removal of solvent, the residue was isolated by silicon gel
chromatography using ethyl acetate/petroleum ether as eluent to give
viscous liquid 5e, 1.74 g, yield 77.8%.
According to the same procedure, the title compound 5f, 5g were
obtained and all compounds prepared were characterized by element
analysis, HNMR and IR spectral data, their relevant data being listed
in Tables I, II, and V.
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