Syntheses and biological activities of S-1,2,4-triazolo[1,5-a]pyrimidinylalkyl dithiophosphates

Article abstract of DOI:10.1002/hc.10198

We introduced dithiophosphate moieties into the fused heterocyclic compound to prepare the title derivatives and characterized their structures by elemental analysis, ¹H NMR, and IR spectral data. We found that these compounds show good fungicidal and herbicidal activities and good plant growth regulation activity.

Full text of DOI:10.1002/hc.10198

Heteroatom Chemistry
Volume 14, Number 7, 2003
S
yntheses and Biological Activities of
S-1,2,4-Triazolo[1,5-a]pyrimidinylalkyl
Dithiophosphates
Wen-Bin Chen and Gui-Yu Jin
The State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic
Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
Received 30 April 2003; revised 19 May 2003
compounds 3 (Scheme 1). The starting compounds
ABSTRACT: We introduced dithiophosphate moi-
1
[4] and 2 [5–8] were prepared as described. Their
eties into the fused heterocyclic compound to pre-
pare the title derivatives and characterized their struc-
tures by elemental analysis, H NMR, and IR spec-
reaction in aqueous sodium hydroxide at room tem-
perature gave 3 (Table 2).
1
tral data. We found that these compounds show good
fungicidal and herbicidal activities and good plant
growth regulation activity. ꢀC 2003 Wiley Periodicals,
Inc. Heteroatom Chem 14:607–611, 2003; Published on-
line in Wiley InterScience (www.interscience.wiley.com).
DOI 10.1002/hc.10198
EXPERIMENTAL
1
H NMR spectra were recorded in CDCl as solvent
3
on an AC-P200 instrument using TMS as an inter-
nal standard. IR spectra were measured on a Nico-
let 5DX IR spectrometer. Elemental analyses were
conducted on an MF-3 automatic analyzer. Melting
points were determined on an MP-500 melting point
apparatus. All temperatures and pressures are un-
corrected.
INTRODUCTION
The substituted 1,2,4-triazolo[1,5-a]pyrimidines are
a class of highly active herbicides [1]. Some prod-
ucts such as DE-498, DE-511, and TP have been com-
mercialized. The herbicide activity is believed to be
due to the inhibition of acetolacetate synthase (ALS),
which participates in the synthesis of branched-
chain amino acids in the plant body [2,3]. As we
all know, organophosphorus compounds possess ac-
tivities such as herbicides, fungicides, and insecti-
cides, but fused heterocyclic compounds containing
phosphorus are seldom reported. To find novel active
compounds, we designed and synthesized the title
The phosphorodithioates 1 were prepared as de-
scribed in literature [4] and their structures were de-
termined by H NMR spectral data (Table 1) and the
triazolopyrimidines 2 were synthesized according to
the known procedure [5,6].
1
Preparation of 3a
To the solution of sodium hydroxide (0.09 g,
2.2 mmol) in 10 ml of water, were added 0.36 g
(2.0 mmol) of 2a and a catalytic amount of tetra-
butyl ammonium bromide (TBAB) and stirred to
give a clear solution. To the mixture was added 1a
in 10 ml of methanol. After being stirred overnight,
the mixture was diluted with 20 ml of chloroform,
the organic phase was separated, and the aqueous
layer was extracted with chloroform (10 ml × 3). The
combined organic phase was washed with water
Correspondence to: Gui-Yu Jin; e-mail: wbchen@nankai.edu.cn.
Contract grant sponsor: National Natural Science Foundation
of China.
Contract grant number: 29832050.
ꢀ
c 2003 Wiley Periodicals, Inc.
6
07

6
08 Chen and Jin
SCHEME 1
(
20 ml × 3) and dried over MgSO
4
. After the solvent
the title compound 3 could not be obtained, only the
ꢁ
1
was removed under reduced pressure, the residue
was purified by silicon gel chromatography with
petroleum ether and ethyl acetate as elution to give
the title compound 3a.
by-product 4 (R = CH
3
, R = H) was obtained. H
NMR δ (ppm, CDCl /TMS) 2.59 (s, 3H, CH
3
3
), 2.69
(s, 3H, CH
3
), 2.71 (s, 3H, CH
3
), 6.73 (s, 1H, CH),
◦
◦
m.p. 155–157 C (lit. [9] 154–155 C). When R was
The other compounds 3 were prepared accord-
ing to the same procedure, and their structures were
determined by elementary analysis, H NMR, and IR
C
2
H
5
and n was 2, compound 3 was obtained in good
yield and the by-product 4 was also obtained. When
R was C , or i-C , the compounds 3 were ob-
1
3
H
7
3
H
7
spectral data and the compound 3f was also charac-
terized by X-ray diffraction. Their data are outlined
in Tables 2–4.
tained, but no by-product 4 was observed, and the
other by-product 5 was separated. H NMR δ (ppm,
1
CDCl
H, 2 × CH
SCH CH CH
3
/TMS) 2.34 (m, 2H, SCH
2
CH
2
CH
2
S), 2.62 (s,
6
3
), 2.74 (s, 6H, 2 × CH
3
), 3.45 (t, 4H,
2
2
2
S), 6.78 (s, 2H, 2 × CH), m/e = 400.
RESULTS AND DISCUSSION
Preparation of 3
When n was 2, the yields were higher than those
when n was 3.
To explain these results, an ionic isomer of 1
may be anticipated, the cyclic cation of which will
easily be attacked by the nucleophilic anion of 2. The
In this reaction, we found that n and R have much
effect on the products. When R was CH
3
and n was 2,
TABLE 1 Physical Data of Phosphorodithionate 1
n25
Yield (%)
1
H NMR δ (ppm, CDCL /TMS)
R
n
D
3
1
a
b
Et
2
1.5341
1.5262
46.2
1.35 (t, 6H, 2 × CH CH O), 3.25 (dt, 2H, CH S), 3.55
3
2
2
(
t, 2H, CH Br), 4.17 (dq, 4H, 2 × CH CH O)
2
3
2
1
Et
3
42.3
1.35 (t, 6H, 2 × CH CH O), 2.19 (m, 2H,
3
2
SCH CH CH Br), 2.98 (m, 2H, SCH CH CH Br),
2
2
2
2
2
2
3
.51 (t, 2H, SCH CH CH Br), 4.13 (m, 4H, 2 ×
2
2
2
CH CH O)
3
2
1
c
d
n-Pr
n-Pr
2
3
1.5228
1.5192
65.6
67.4
0.93 (t, 6H, 2 × CH CH CH O), 1.67 (t, 4H, 2 ×
3
2
2
CH CH CH O), 3.18 (dt, 2H, SCH CH Br), 3.52 (t,
3
2
2
2
2
2
H, CH Br), 4.04 (m, 4H, 2 × CH CH CH O)
2
3
2
2
1
0.96 (t, 6H, 2 × CH CH CH O), 1.71 (t, 4H, 2 ×
3
2
2
CH CH CH O), 2.21 (m, 2H, SCH CH CH Br), 3.01
3
2
2
2
2
2
(
(
m, 2H, SCH CH CH Br), 3.48 (t, 2H, CH Br), 4.04
2 2 2 2
m, 4H, 2 × CH CH CH O)
3
2
2
1
1
e
f
i -Pr
i -Pr
2
3
1.5149
1.5122
67.2
59.8
1.31 (d, 12H, 2 × (CH ) CHO), 3.24 (m, 2H,
3
2
SCH CH Br), 3.49 (t, 2H, SCH CH Br), 4.78 (m, 2H,
2
2
2
2
2
× (CH ) CHO)
3
2
1.33 (d, 12H, 2 × (CH ) CHO), 2.19 (m, 2H,
3
2
SCH CH CH Br), 3.00 (dt, 2H, SCH CH CH Br),
2
2
2
2
2
2
3
.46 (t, 2H, CH Br), 4.82 (m, 2H, 2 × (CH ) CHO)
2
3 2

Syntheses and Biological Activities of S-1,2,4-Triazolo[1,5-a]pyrimidinylalkyl Dithiophosphates 609
TABLE 2 Physical Data of 3a–3k
Analysis (%, Calcd)
ꢁ
◦
n
R
R
m.p. ( C)
Yield (%)
C
H
N
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
2
3
2
3
2
3
2
2
3
2
3
Et
Et
H
H
H
H
H
68–70
25–27
49–50
36–38
64–65
80.4
61.6
72.6
56.5
74.8
44.9
57.9
53.2
48.4
49.7
41.9
39.74 (39.79)
41.49 (41.38)
42.74 (42.86)
44.13 (44.24)
42.85 (42.86)
44.43 (44.24)
41.30 (41.38)
44.21 (44.24)
45.27 (45.54)
44.18 (44.24)
45.38 (45.54)
5.24 (5.36)
5.54 (5.67)
5.65 (5.95)
6.38 (6.22)
5.84 (5.95)
6.16 (6.22)
5.42 (5.67)
6.01 (6.22)
6.34 (6.47)
5.99 (6.22)
6.47 (6.47)
14.03 (14.29)
13.75 (13.79)
13.23 (13.33)
12.73 (12.91)
13.27 (13.33)
12.66 (12.91)
13.78 (13.79)
13.05 (12.91)
12.35 (12.50)
13.12 (12.91)
12.63 (12.50)
n-Pr
n-Pr
i -Pr
i -Pr
Et
n-Pr
n-Pr
i -Pr
i -Pr
H
61–63
Me
Me
Me
Me
Me
Thick liquid
Thick liquid
Thick liquid
Thick liquid
68–69
j
k
TABLE 3 IR Data of 3
IR (KBr or film, cm 1)
−
P S
P S
P O C
C H
C C, C N
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
650.9
653.9
657.9
657.8
648.5
651.3
654.8
656.3
657.7
649.2
648.2
530.8
538.4
542.3
540.9
553.3
542.3
537.5
534.6
530.1
538.3
532.7
1013.0, 1152.0, 786.3
1006.4, 1154.6, 783.7
973.7, 1150.0, 772.4
978.7, 1146.2, 772.3
985.1, 1173.9, 771.8
984.4, 1172.6, 772.2
1006.8, 1154.0, 764.7
974.5, 1158.5, 770.7
974.8, 1156.9, 771.2
985.3, 1171.7, 770.9
983.8, 1172.6, 770.3
3046.5
3037.4
3039.5
3047.0
3036.2
3067.5
–
1628.0, 1549.9, 1442.0
1618.7, 1544.8, 1439.4
1628.6, 1548.8, 1448.6
1640.9, 1549.2, 1445.8
1625.1, 1549.4, 1448.2
1621.9, 1548.4, 1437.5
1614.0, 1526.7, 1438.5
1612.5, 1525.5, 1460.0
1618.2, 1543.8, 1433.8
1612.7, 1525.9, 1461.2
1636.6, 1540.7, 1448.8
–
–
–
–
j
k
TABLE 4 1H NMR Spectral Data of 3
1
H NMR δ (ppm, CDCl /TMS)
3
3a
3b
3c
3d
1.34 (t, 6H, 2 × CH CH O), 2.66, 2.77 (ds, 6H, 2 × CH ), 3.36 (m, 2H, SCH CH SP), 3.57 (t, 2H, SCH CH SP),
3
2
3
2
2
2
2
4
.17 (m, 4H, 2 × CH CH O), 6.87 (s, 1H, CH)
3
2
1.23 (t, 6H, 2 × CH CH O), 2.09 (m, 2H, SCH CH CH SP), 2.49, 2.61 (ds, 6H, 2 × CH ), 2.89 (dt, 2H,
3
2
2
2
2
3
SCH CH CH SP), 3.24 (t, 2H, SCH CH CH SP), 4.06 (dq, 4H, 2 × CH CH O), 6.65 (s, 1H, CH)
2
2
2
2
2
2
3
2
0.94 (t, 6H, 2 × CH CH CH O), 1.71 (m, 4H, 2 × CH CH CH O), 2.61, 2.72 (ds, 6H, 2 × CH ), 3.31 (dt, 2H,
3
2
2
3
2
2
3
SCH CH SP), 3.31 (t, 2H, SCH CH SP), 4.04 (m, 4H, 2 × CH CH CH O), 6.73 (s, 1H, CH)
2
2
2
2
3
2
2
0.93 (t, 6H, 2 × CH CH CH O), 1.69 (m, 4H, 2 × CH CH CH O), 2.19 (m, 2H, SCH CH CH SP), 2.61, 2.71 (ds,
3
2
2
3
2
2
2
2
2
6
6
H, 2 × CH ), 3.01 (dt, 2H, SCH CH CH SP), 3.35 (t, 2H, SCH CH CH SP), 4.02 (m, 4H, 2 × CH CH CH O),
3
2
2
2
2
2
2
3
2
2
.71 (s, 1H, CH)
3
3
3
3
3
3
3
e
1.32 (d, 12H, 2 × (CH ) CHO), 2.62, 2.72 (ds, 6H, 2 × CH ), 3.32 (m, 2H, SCH CH SP), 3.55 (t, 2H, SCH CH SP),
3
2
3
2
2
2
2
4
.81 (m, 2H, 2 × (CH ) CHO), 6.75 (s, 1H, CH)
3
2
f
1.32 (d, 12H, 2 × (CH ) CHO), 2.19 (m, 2H, SCH CH CH SP), 2.60, 2.71 (ds, 6H, 2 × CH ), 3.06 (m, 2H,
3
2
2
2
2
3
SCH CH CH SP), 3.35 (t, 2H, SCH CH CH SP), 4.79 (m, 2H, 2 × (CH ) CHO), 6.71 (s, 1H, CH)
2
2
2
2
2
2
3 2
g
h
i
1.34 (t, 6H, 2 × CH CH O), 2.31, 2.62, 2.75 (ts, 9H, 3 × CH ), 3.33 (m, 2H, SCH CH SP), 3.53 (t, 2H,
3
2
3
2
2
SCH CH SP), 4.19 (m, 4H, 2 × CH CH O)
2
2
3
2
0.94 (t, 6H, 2 × CH CH CH O), 1.73 (m, 4H, 2 × CH CH CH O), 2.29, 2.59, 2.73 (ts, 9H, 3 × CH ), 3.28 (dt, 2H,
3
2
2
3
2
2
3
SCH CH SP), 3.51 (t, 2H, SCH CH SP), 4.04 (m, 4H, 2 × CH CH CH O)
2
2
2
2
3
2
2
0.93 (t, 6H, 2 × CH CH CH O), 1.72 (m, 4H, 2 × CH CH CH O), 2.18 (m, 2H, SCH CH CH SP), 2.29, 2.59, 2.73
3
2
2
3
2
2
2
2
2
(
ts, 9H, 3 × CH ), 2.99 (m, 2H, SCH CH CH SP), 3.34 (t, 2H, SCH CH CH SP), 4.06 (m, 4H, 2 × CH CH CH O)
3
2
2
2
2
2
2
3
2
2
j
1.32 (d, 12H, 2 × (CH ) CHO), 2.28, 2.59, 2.73 (ts, 9H, 3 × CH ), 3.36 (m, 2H, SCH CH SP), 3.53 (t, 2H,
3
2
3
2
2
SCH CH SP), 4.83 (m, 2H, 2 × (CH ) CHO)
2
2
3 2
k
1.32 (d, 12H, 2 × (CH ) CHO), 2.23 (m, 2H, SCH CH CH SP), 2.29, 2.60, 2.74 (ts, 9H, 3 × CH ), 3.07 (m, 2H,
3
2
2
2
2
3
SCH CH CH SP), 3.35 (t, 2H, SCH CH CH SP), 4.79 (m, 2H, 2 × (CH ) CHO)
2
2
2
2
2
2
3 2

6
10 Chen and Jin
FIGURE 1 Molecular structure of 3f.
attack of different carbon atoms of the cation will
result in the products 3, 4, and 5. Because of differ-
ent steric hindrance, the different starting materials
reacted with nucleophile 2 to obtain particular
products.
tal X-ray diffraction analysis (Fig. 1) [12]. We find
that the fused heterocyclic structure is triazolo[1,5-
a]pyrimidine and not triazolo[4,3-a]pyrimidine. The
triazolopyrimidine rings are almost coplanar, and
the bond lengths of N C are shorter than that of the
˚
normal C N bond (1.47 A), but very close to that of
˚
the C N bond (1.33 A), indicating that all C and N
Structure of 3f
2
atoms are sp -hybridized.
Okabe et al. [10] once reported that 3-amino-5-
mercapto-1,2,4-triazole reacted with acetylacetone
in acetic acid on refluxing to give 1,2,4-triazolo[4,3-
a]pyrimidine. But Novinson et al. [11] described
that in this reaction, the final product should be
Biological Activity of 3
From the screening results of biological activities,
we found that most compounds show good fungici-
dal activities against Phoma asparagi, highly active
herbicide on rape at postemergence, and good plant
growth regulation to rooting of cucumber cotyledon.
These data are outlined in Table 5.
1
3
1,2,4-triazolo[1,5-a]pyrimidine 2 via C NMR spec-
troscopy. Even though there was 1,2,4-triazolo[4,3-
a]pyrimidine in the reaction, it can rearrange to
2
on mild conditions. To determine the structure,
we selected compound 3f to make a single crys-
TABLE 5 Biological Activities of Some Compounds 3
a
Fungicidal (50 ppm) (%)
Herbicidal (1.5 kg/ha) (%)
PGR (10 ppm) (%)
Medicago
sativa Lam
Rooting of Cucumber
Cotyledon
Phoma asparagi
Rape
3
3
3
3
3
3
a
b
c
e
g
k
75.0
75.0
81.2
75.0
81.2
75.0
54.8
85.4
97.6
63.4
100
49.3
47.8
35.8
19.4
92.5
86.6
130.8
107.7
53.8
100
92.3
84.6
100
aPGR: Plant growth regulation.

Syntheses and Biological Activities of S-1,2,4-Triazolo[1,5-a]pyrimidinylalkyl Dithiophosphates 611
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