Synthesis and Biological Activity of O-Methyl Methyl 1-(Substituted Phenoxyacetoxy)-1-(thien-2-yl)methylphosphinates

Article abstract of DOI:10.1002/jhet.2143

A series of novel O-methyl methyl 1-(substituted phenoxyacetoxy)-1-(thien-2-yl)methylphosphinates 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h were synthesized. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays show that some of the title compounds exhibit moderate to good herbicidal and fungicidal activities. For example, the title compounds 5c, 5d, and 5g possess 90-100% inhibition against the tested plants at the concentration of 10 mg/L and 100 mg/L, whereas the title compounds 5a, 5b, 5c, and 5h possess 70-94% inhibition against Phyricularia grisea and Sclerotinia sclerotiorum at the concentration of 50 mg/L.

Full text of DOI:10.1002/jhet.2143

Month 2014
Synthesis and Biological Activity of O-Methyl Methyl 1-
(
Substituted Phenoxyacetoxy)-1-(thien-2-yl)methylphosphinates
Tao Wang, Hao Peng, and Hongwu He*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, and College of Chemistry, Central China
Normal University, Wuhan, People’s Republic of China
*
E-mail: he1208@mail.ccnu.edu.cn
Received August 19, 2013
DOI 10.1002/jhet.2143
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel O-methyl methyl 1-(substituted phenoxyacetoxy)-1-(thien-2-yl)methylphosphinates
1
5
a–h were synthesized. Their structures were confirmed by IR, H NMR, mass spectroscopy, and elemental
analyses. The results of preliminary bioassays show that some of the title compounds exhibit moderate to
good herbicidal and fungicidal activities. For example, the title compounds 5c, 5d, and 5g possess
9
0–100% inhibition against the tested plants at the concentration of 10 mg/L and 100 mg/L, whereas the title
compounds 5a, 5b, 5c, and 5h possess 70–94% inhibition against Phyricularia grisea and Sclerotinia
sclerotiorum at the concentration of 50 mg/L.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
RESULTS AND DISCUSSION
α-Substituted alkylphosphonate derivatives have re-
ceived considerable attention in medicine and pesticide
chemistry due to their biological activities over the past
two decades [1–4]. Especially, in our previous work, a se-
ries of 1-(substituted phenoxyacetoxy)alkylphosphonates,
as potent pyruvate dehydrogenase complex inhibitors,
were synthesized and showed notable bioactivities [5–7].
Substituted pyridine and thiophene derivatives, as an im-
portant class of agrochemicals, have played a major role
in crop protection. And as typical heterocyclic groups,
pyridinyl and thienyl are often introduced in the design
of bioactive compounds [8–10]. Therefore, a series of O,
O-dimethyl 1-(substituted phenoxyacetoxy)-1-(pyrid-2-yl
or thien-2-yl)methylphosphonates were synthesized, and
some of them exhibited excellent herbicidal and fungicidal
activities [11].
On the other hand, bioisosterism is an important
concept of bioactive compound design[12,13]. The
phosphinate group is often used for bioisosteric replace-
ment of phosphonate group in bioactive molecules to
obtain more bioactivity or safety, which encouraged us
to replace the phosphonate group with phosphinate group
and further study the structure–activity relationship.
Herein, we reported the synthesis of new O-methyl
methyl 1-(substituted phenoxyacetoxy)-1-(thien-2-yl)
methylphosphinates 5 (Scheme 1) and their evaluation
for herbicidal and fungicidal activities.
The reaction of O,O-dialkyl phosphonates with alde-
hydes is a convenient method used to synthesize 1-
hydroxyphosphonates, which have been reported in many
literatures [14–16]. However, there are few reports on
the reaction of O-methyl methylphosphinate 1 with
thiophene-2-carbaldehyde. On the basis of the synthetic
method of 1-hydroxyphosphonates, 1-hydroxyphosphinate
2 was synthesized by the reaction of intermediate 1 with
thiophene-2-carbaldehyde using triethylamine as a catalyst.
Triethylamine is an important catalyst, which is essential to
the addition reaction mentioned earlier. Without the use of
the triethylamine as a catalyst, the reaction was greatly
slowed, and the yields were very low. The title compounds
5a–h were prepared by condensation of intermediates 2
with substituted phenoxyacetyl chlorides 4 in the presence
of triethylamine as a base in chloroform (Scheme 1).
1
The structures of 5a–h were characterized by H NMR,
IR, MS, and elemental analysis. Compound 5h was further
31
1
analyzed by P NMR. The H NMR spectrum shows that
the proton signals corresponding to methyl, methoxy, and
methylidyne attached to phosphorus appear as two
doublets, respectively. For example, the CH signals of
3
compound 5a appear at δ 1.49 (d, J = 14.8 Hz), 1.56 (d,
J = 14.8 Hz), the CH O signals at δ 3.69 (d, J = 12.4 Hz),
3
3.75 (d, J = 12.4 Hz), and CH signal at
δ 6.50
(d, J = 10.8 Hz), 6.58 (d, J = 10.8 Hz), respectively. The
magnetic nucleus phosphorus makes these proton signals
©
2014 HeteroCorporation

T. Wang, H. Peng, and H. He
Vol 000
Scheme 1. Synthetic route of compounds 5a–h.
As shown in Table 1, 5c, 5d, and 5g displayed notable
herbicidal activity against the tested plants, with more than
9
0% inhibitory rate to the growth of the stem and the root at
the concentration of 10mg/L. The title compounds showed
higher inhibitory activities against the growth of the root
than that of the stem. For example, compounds 5c–5d
showed 96% inhibitory rate against the root of E. crusgalli
at the concentration of 10mg/L but only 36–46% inhibitory
rate against the stem of E. crusgalli at the same
concentration. Comparing herbicidal activities among the
title compounds in Table 1, it was found that the X and Y
groups have great impact on the herbicidal activity. The title
compounds with 4-Cl, 3-CH -4-Cl, and 2,4-Cl as Y (5c,
3
2
n
5
d, and 5g) show higher inhibitory rate (>90%) against the
root of the tested plants at the concentration of 10 mg/L.
Fungicidal activity. The fungicidal activities of 5a–h
split into a doublet, and the low rate of environment
exchange caused by the slow rotation of the P–C bond
is the probable reason for two doublets signals. And
the signal strength of these two doublets is different,
which indicates that the ratio of two conformations is
different. The signal corresponding to the methylene
were evaluated by the classic plate method at the
concentration of 50 mg/L, which was described in the
experimental part. The six fungi Fusarium oxysporum
(Fusarium wilt), Phyricularia grisea (Rice blast), Botrytis
cinereapers (Gray mold), Gibberella zeae (Telomorph),
Sclerotinia sclerotiorum (Sclerotiniose), and Cercospora
beticola (Brown spot), belong to the group of field fungi
and were isolated from corresponding crops. As listed in
Table 2, most compounds display moderate to good
fungicidal activity against the six aforementioned fungi.
For example, compounds 5c and 5h possessed more than
88% inhibitory activity against rice blast and sclerotiniose.
group (CH ) flanked by the phenoxy group, and carbonyl
2
group appears as a quartet, the outside peaks smaller in
size, which belongs to the AB system with the difference
in chemical shift between the two mutually coupled
protons A and B.
The corresponding IR spectrum revealed normal absorption
À1
À1
bands at 1740–1770 cm
(C═O) and 3060–3090 cm
It was found that Y groups on the phenoxy ring had great
n
(Ar–H). The mass spectra of the title compound 5 revealed
impact on the fungicidal activity. As for rice blast and
the existence of the molecular ion peaks, which were in good
accordance with the given structures of products.
sclerotiniose, 4-Cl and 2,6-Cl groups on the phenoxy ring
2
was the most promotive, followed by 3-CF and 2-F.
3
Biological activities
Herbicidal activity. The preliminary herbicidal activity
of 5a–h was evaluated against Brassica napus (rape) and
Echinochloa crus-galli (barnyard grass) at the concentration
of 100 mg/L and 10 mg/L using the known procedure [17].
In conclusion, a series of novel O-methyl methyl 1-
(substituted phenoxyacetoxy)-1-(thien-2-yl)methylphosphi-
nates 5a–h were designed and synthesized. The results of
preliminary bioassays showed that compounds 5c, 5d, and
5g displayed notable herbicidal activity against the tested
Table 1
Structure and herbicidal activity of compound 5.
Ech
Bra
Stem
Root
Stem
Root
No.
Y
n
10 mg/L
100 mg/L
10 mg/L
100 mg/L
10 mg/L
100 mg/L
10 mg/L
100 mg/L
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
3-CF
2-F
4-Cl
3-CH
3
39
57
46
36
57
68
39
68
64
61
64
54
61
82
89
68
47
71
96
96
58
60
98
76
93
80
98
98
82
96
98
87
49
À8
92
95
8
3
97
21
97
31
97
97
56
54
100
92
60
4
99
100
40
26
99
72
100
100
94
93
100
97
3
,4-Cl
2-Cl,5-CH
3
2,3-Cl
2,4-Cl
2,6-Cl
2
2
2
100
47
Ech: Echinochloa crus-galli; Bra, Brassica napus.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis and Bioactivity of 1-(Substituted Phenoxyacetoxy)-1-(thien-2-yl)
methylphosphinates
Table 2
and thionyl chloride (4 mL) was added into a 15-mL flask and
refluxed for 5–6 h. Excess thionyl chloride was evaporated off
under reduced pressure, and a light yellow oil 4 was obtained
with a yield of 85–90%, which was used directly without
further purification.
Fungicidal activity of compound 5.
No.
Y
n
Fus
Phy
Bot
Gib
Scl
Cer
5
5
5
5
5
5
5
5
a
b
c
d
e
f
g
h
3-CF
3
61
43
39
26
35
30
35
57
71
43
57
29
36
50
29
50
84
72
91
41
38
59
19
88
41
41
56
29
29
41
24
47
71
82
94
71
59
65
41
88
46
46
54
39
32
29
21
46
General procedure for the synthesis of title compounds
2-F
4-Cl
5
a–h.
A solution of substituted phenoxyacetyl chlorides 4
(
3.3 mmol) in dichloromethane (15 mL) was added to a
3-CH
3
,4-Cl
stirred mixture of O-methyl methyl 1-hydroxy-1-(thien-2-yl)
methylphosphinate 2 (3 mmol) and triethylamine (3.3 mmol) in
chloroform (20mL) at 20–25°C. The resultant mixture was stirred
for 3–5 h at room temperature and then for 1–2 h at 40°C. The
dichloromethane layer was washed with 0.1 M hydrochloric acid,
saturated sodium hydrogen carbonate solution and brine, dried,
and concentrated. The residue was purified by column
chromatography on silica gel and elution with petroleum ether/
acetone (4:1, v/v) to give the corresponding pure title compounds
2-Cl,5-CH
3
2,3-Cl
2,4-Cl
2,6-Cl
2
2
2
Fus: Fusarium oxysporum; Phy: Phyricularia grisea; Bot: Botrytis
cinereapers; Gib: Gibberella zeae; Scl: Sclerotinia sclerotiorum; Cer:
Cercospora beticola;
1
plants, with more than 90% inhibitory rate to the growth of
the stem and the root at the concentration of 10 mg/L. In
addition, compounds 5c and 5h possessed more than 88%
inhibitory activity against rice blast and sclerotiniose. These
results indicated that the title compound 5 could be modified
and used as lead compounds for further study.
5a–h. Their structures were confirmed by H NMR, IR, MS, and
elemental analysis. And the physicochemical properties and
spectroscopic data for compounds 5a–h are as follows.
Data for O-methyl methyl 1-(thioen-2-yl)-1-(3-trifluoromethyl-
phenoxyacetoxy)methylphosphinate (5a).
Yellowish oil, yield,
0
À1
6
1
2%; n2 , 1.5421; IR (KBr, cm ): ν 3079, 2953, 2851, 1743,
D
1
593, 1456, 1428, 1224, 1173, 1043, 897, 719. H NMR
(
400 MHZ, CDCl ) δ 1.49, 1.56 (d, 3H, CH , J= 14.8 Hz), 3.69,
3
3
3
.75 (d, 3H, OCH
3
, J= 12.4 Hz), 4.80, 4.87 (q, AB system, 2H,
EXPERIMENTAL
2
OCH CO, JAB = 15.4 Hz), 6.50, 6.58 (d, 1H, OCHP, J= 10.8 Hz),
+
6
2
.92–7.37 (m, 7H, ArH); MS m/z (%): 408 (M , 5.63), 315 (1.05),
05 (6.65), 189 (8.28), 175 (36.30), 161 (1.47), 145 (76.68), 111
Chemicals and reagents were obtained from commercial sources,
and all of the solvents were dried and purified by standard techniques
prior to use. Column chromatography was carried out with Merck
(49.37), 93 (100), 63 (56.77). Anal. Calcd for C H F O PS: C,
16 16 3 5
2
0
47.06; H, 3.95. Found: C, 46.65; H, 4.40.
silica gel (200–300 meshes). Refractive index (n ) was measured
D
Data for O-methyl methyl 1-(2-fluorophenoxyacetoxy)-1-
thioen-2-yl)methylphosphinate (5b). Yellowish oil, yield,
66%; n , 1.5240; IR (KBr, cm ): ν 3074, 2924, 2852, 1741,
on an Abbe refractometer and was uncorrected. IR spectra were
recorded as KBr pellets on a Perkin-Elmer Fourier transform infrared
(
2
0
À1
1
31
spectrophotometer (USA). H NMR and P NMR were recorded
on Varian XL-400 spectrometer (Salt Lake City, USA) at
D
1
1
592, 1506, 1428, 1226, 1174, 1040, 898, 753. H NMR
) δ 1.48, 1.55 (d, 3H, CH , J= 14.4 Hz), 3.69,
.75 (d, 3H, OCH , J= 12.4 Hz), 4.79, 4.86 (q, AB system, 2H,
(400 MHZ, CDCl
3
3
4
00 MHz using tetramethylsilane as internal standard (solvent
CDCl ). Chemical shifts (δ) are given in ppm, coupling constants
J) are in Hz, and multiplicities are implicated by s (singlet), d
doublet), t (triplet), q (quartet), and m (multiplet). MS spectra were
analyzed on a Finnigan TRACE spectrometer (Ramsey, USA) and
API2000LC/MS (Framingham, USA). Elemental analyses were
performed by a Vario EL III elemental analyzer (Hanau, Germany).
3
3
3
OCH CO, J = 15.0 Hz), 6.52, 6.60 (d, 1H, OCHP, J= 10.8 Hz),
6.90–7.36 (m, 7H, ArH); MS m/z (%): 358 (M , 2.26), 205 (5.32),
170 (48.16), 125 (67.78), 111 (38.07), 93 (100), 63 (80.45). Anal.
(
(
2
AB
+
Calcd for C15
Data for O-methyl methyl 1-(4-chlorophenoxyacetoxy)-1-
thioen-2-yl)methylphosphinate (5c). Yellowish oil, yield,
H16FO PS: C, 50.28; H, 4.50. Found: C, 50.67; H, 4.56.
5
(
7
1
Procedure for the synthesis of intermediate 2. A solution
of dichloro(methyl)phosphine (5.85 g, 50 mmol) in dry benzene
2
0
À1
0%; n , 1.4868; IR (KBr, cm ): ν 3092, 2924, 2852, 1739,
D
1
596, 1492, 1429, 1236, 1174, 1042, 899, 709. H NMR
(
40 mL) was added dropwise with stirring to a cooled solution
of methanol (3.84 g, 120 mmol) and triethylamine (5.05 g,
0.0 mmol) under nitrogen at 0–5°C. After allowing the reaction
mixture to stand for 1 h and then filtered, the filtrate was
condensed to give O-methyl methylphosphinate 1, which was
used directly without further purification.
solution of O-methyl methylphosphinate
0.0 mmol) prepared earlier in dry benzene (20 mL) was added
with stirring to a solution of thiophene-2-carbaldehyde (2.69 g,
4.0 mmol) and catalyst triethylamine (1.01 g, 10.0 mmol) under
nitrogen at 0–5°C. After the reaction mixture was stirred for
–8 h at 50–60°C, the solvent was removed under reduced
pressure. The residue was purified by column chromatography
on silica gel and elution with petroleum ether/acetone (3:1, v/v) to
give O-methyl methyl 1-hydroxy-1-(thien-2-yl)methylphosphinate 2.
General procedure for the synthesis of intermediates 4.
mixture containing substituted phenoxyacetyl acid 3 (4.0 mmol)
(
400 MHZ, CDCl ) δ 1.47, 1.54 (d, 3H, CH , J = 14.4 Hz), 3.68,
3
3
3
.74 (d, 3H, OCH , J = 12.4 Hz), 4.80, 4.87 (q, AB system, 2H,
3
2
CO, JAB = 15.6 Hz), 6.45, 6.53 (d, 1H, OCHP, J = 9.8 Hz),
.85–7.39 (m, 7H, ArH); MS m/z (%): 374 (M , 15.62), 205
5
OCH
6
+
(
24.10), 189(59.65), 141 (43.40), 111 (100), 93 (86.24), 63
(
60.88). Anal. Calcd for C H ClO PS: C, 48.07; H, 4.30.
15
16
5
A
1 (1.88 g,
Found: C, 47.95; H, 4.00.
2
Data for O-methyl methyl 1-(4-chloro-3-methylpheno-
xyacetoxy)-1-(thioen-2-yl)methylphosphinate (5d). Yellowish
oil, yield, 72%; n , 1.5423; IR (KBr, cm ): ν 3059, 2955, 2851,
2
2
0
À1
D
1
1
(
(
771, 1590, 1493, 1436, 1224, 1170, 1041, 900, 748. H NMR
400 MHZ, CDCl ) δ 1.47, 1.54 (d, 3H, CH , J= 14.0 Hz), 2.28
s, 3H, cPhCH ), 3.69, 3.75 (d, 3H, OCH , J= 12.4 Hz), 4.78, 4.85
6
3
3
3
3
(q, AB system, 2H, OCH CO, J = 15.4 Hz), 6.52, 6.60 (d, 1H,
2 AB
A
OCHP, J= 10.4 Hz), 6.90–7.36 (m, 6H, ArH); MS m/z (%): 388
(M , 3.06), 205 (1.88), 189(8.65), 155 (18.06), 141 (20.17), 125
+
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

T. Wang, H. Peng, and H. He
Vol 000
(
40.78), 111 (32.17), 93 (100), 63 (88.47). Anal. Calcd for
at 28°C for 3 days with 10 h of lighting and 14 h in the dark.
The experiments were conducted in three replicates. The
lengths of roots and shoots were measured after 72 h of
treatment, and the growth inhibitory rate related to untreated
control was determined.
C H ClO PS: C, 49.43; H, 4.67. Found: C, 49.56; H, 4.21.
16
18
5
Data for O-methyl methyl 1-(2-chloro-5-methylpheno-
xyacetoxy)-1-(thioen-2-yl)methylphosphinate (5e). Yellowish
oil, yield, 75%; n , 1.5382; IR (KBr, cm ): ν 3077, 2957, 2853,
2
0
À1
D
1
1
770, 1580, 1456, 1435, 1271, 1180, 1051, 891, 772. H NMR
The fungicidal activity measurement method was adapted from
Ref [11]. The phosphonates were dissolved in DMF (0.5–1.0 mL)
to the concentration of 1000 mg/L. The solutions (1 mL) were
mixed rapidly with thawed potato glucose agar culture medium
(9 mL) under 50°C. The mixtures were poured into Petri dishes.
After the dishes were cooled, the solidified plates were incubated
with 4-mm mycelium disk, inverted and incubated at 28°C for
48 h. Distilled water was used as the blank control. Three repli-
cates of each test were carried out. The mycelial elongationradius
(millimeter) of fungi settlements was measured after 48 h of
culture. The growth inhibitory rates were calculated with the
following equation: I = [(C À T)/C] × 100%. Here, I is the growth
inhibitory rate (%), T is the treatment group fungi settlement
radius (millimeter), and C is the radius of the blank control.
(400 MHZ, CDCl ) δ 1.49, 1.53 (d, 3H, CH , J= 13.8 Hz), 2.27
3
3
(
(
s, 3H, PhCH
q, AB system, 2H, OCH
OCHP, J= 10.4 Hz), 6.68–7.27 (m, 6H, ArH); MS m/z (%): 388
3 3
), 3.70, 3.77 (d, 3H, OCH , J= 12.4 Hz), 4.78, 4.85
2
CO, JAB = 15.4 Hz), 6.56, 6.62 (d, 1H,
+
(
(
C
M , 1.77), 205 (3.04), 189(6.17), 155 (20.88), 141 (5.73), 125
35.97), 111 (49.39), 93 (100), 63 (59.87). Anal. Calcd for
18ClO PS: C, 49.43; H, 4.67. Found: C, 49.55; H, 4.66.
Data for O-methyl methyl 1-(2,3-dichlorophenoxyacetoxy)-1-
thioen-2-yl)methylphosphinate (5f). Yellowish oil, yield,
16
H
5
(
2
0
À1
6
1
(
3
1%; n , 1.5241; IR (KBr, cm ): ν 3081, 2955, 2852, 1770,
D
1
579, 1458, 1436, 1232, 1178, 1042, 893, 771. H NMR
400 MHZ, CDCl
3
) δ 1.45, 1.50 (d, 3H, CH
3
, J = 14.4 Hz), 3.67,
.73 (d, 3H, OCH
3
, J = 12.4 Hz), 4.81, 4.88 (q, AB system, 2H,
OCH CO, J = 15.4 Hz), 6.44, 6.52 (d, 1H, OCHP, J = 8.8 Hz),
2
AB
+
6
(
1
.75–7.39 (m, 6H, ArH); MS m/z (%): 408 (M , 4.68), 315
2.11), 205 (2.46), 203 (1.17), 189(2.17), 175 (17.02), 161 (3.44),
45 (18.83), 111 (66.65), 93 (100), 63 (43.64). Anal. Calcd for
PS: C, 44.03; H, 3.69. Found: C, 43.72; H, 3.72.
Data for O-methyl methyl 1-(2,4-dichlorophenoxyacetoxy)-1-
thioen-2-yl)methylphosphinate (5g). Yellowish oil, yield,
Acknowledgments. This research was supported in part by the
National Basic Research Program of China (No. 2010CB126100),
the National Key Technologies R & D Program of China
15 2 5
C H15Cl O
(
No.2011BAE06B03), and the National Natural Science
(
Foundation of China (No. 21172090). The research was also
supported in part by the PCSIRT (No. IRT0953).
2
0
À1
6
4%; n , 1.5121; IR (KBr, cm ): ν 3075, 2923, 2852, 1749,
D
1
1
584, 1478, 1437, 1246, 1182, 1042, 898, 756. H NMR
(
400 MHZ, CDCl
3
) δ 1.47, 1.62 (d, 3H, CH
3
, J = 15.6 Hz), 3.68,
3
.74 (d, 3H, OCH , J = 12.4 Hz), 4.80, 4.87 (q, AB system, 2H,
3
REFERENCES AND NOTES
OCH CO, JAB = 15.0 Hz), 6.49, 6.54 (d, 1H, OCHP,
J = 10.4 Hz), 6.72–7.40 (m, 6H, ArH); MS m/z (%): 408 (M ,
2
+
[
1] Makarov, M. V.; Rybalkina, E. Y.; Röschenthaler, G. V.;
1
1.68), 315 (4.96), 309 (6.61), 205 (7.96), 203 (2.51), 189
Short, K. W.; Timofeeva, T. V.; Odinets, I. L. Eur J Med Chem 2009,
44, 2135.
(
9.07), 175 (31.71), 161 (6.46), 145 (32.14), 111 (79.22), 93
[
2] Koh, Y., Shim, J. H.; Wu, J. Z.; Zhong, W. D.; Hong, Z.;
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(
100), 63 (41.93). Anal. Calcd for C H Cl O PS: C, 44.03; H,
1
5
15
2 5
3
.69. Found: C, 44.40; H, 3.72.
Data for O-methyl methyl 1-(2,6-dichlorophenoxyacetoxy)-1-
thioen-2-yl)methylphosphinate (5h). Yellowish oil, yield,
[
(
[
2
0
À1
6
3%; n , 1.5186; IR (KBr, cm ): ν 3076, 2954, 2851, 1775,
Besra, G. S.; Soares, S. L.; Appelberg, R.; Kikelj, D. Eur J Med Chem
2007, 42, 54.
[5] Peng, H.; Wang, T.; Xie, P.; Chen, T.; He, H. W. J Agric Food
Chem 2007, 55, 1871.
D
1
1
568, 1456, 1439, 1227, 1175, 1042, 895, 786. H NMR
(
400 MHZ, CDCl ) δ 1.51, 1.57 (d, 3H, CH , J = 14.0 Hz), 3.70,
3
3
3
.77 (d, 3H, OCH
3
, J = 10.8 Hz), 4.75, 4.82 (q, AB system, 2H,
[
6] He, H. W.; Yuan, J. L.; Peng, H.; Chen, T.; Shen, P.; Wan,
S. Q.; Li, Y. J.; Tan, H. L.; He, Y. H.; He, J. B.; Li, Y. J Agric Food Chem
011, 59, 4801.
OCH
.03–7.40 (m, 6H, ArH);
δ = 46.1, 46.6; MS m/z (%): 408 (M , 5.89), 315 (4.97), 205
2
CO, JAB = 14.8 Hz), 6.51, 6.60 (d, 1H, OCHP, J = 7.6 Hz),
3
1
7
3
P NMR (CDCl , 162 MHz):
2
+
[7] He, H. W.; Chen, T.; Li, Y. J. J Pestic Sci 2007, 32, 42.
(
6.50), 203 (1.28), 189(5.12), 175 (22.93%), 161 (1.09), 145
[8] Al-Omran, F. A.; Ei-Khair, A. A. J. Heterocyclic Chem 2008,
(
C
26.87), 111 (74.13), 93 (100), 63 (41.72). Anal. Calcd for
45, 1057.
[9] Matondo, H.; Benevides, N.; Tissut, M.; Bergon, M.;
Savignac, A.; Calmon, J. P.; Lattes, A. J Agric Food Chem 1989, 37, 169.
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Guan, H. J Agric Food Chem 2006, 54, 125.
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15
H
15Cl
2
O
5
PS: C, 44.03; H, 3.69. Found: C, 43.55; H, 3.74.
Biological activity testing. The preliminary herbicidal
[
activity of title compounds 5a–h was measured according to the
modified method described previously [17]. A set amount of
each sample was dissolved in N, N-dimethylformamide (DMF)
to which a drop of an emulsifier, Tween 80, was added. The
solution was then diluted with water until it reached the
concentrations required. The amounts of DMF and the emulsifier
were set as low as possible but still sufficient to make a uniform
emulsion even at high concentrations. A solution (5 mL) was
placed on a filter paper (diameter = 5.5 cm) in Petri dishes
[
Chem. DOI: 10.1002/jhet.1944
[12] Burger, A. Prog Drug Res 1991, 37, 288.
[
[
[
13] Meanwell, N. A. J. Med Chem 2011, 54, 2529.
14] Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 1982, 916.
15] Chen, T.; Shen, P.; Li, Y. J.; He, H. W. J Fluorine Chem 2006,
127, 291.
[16] Wang, C. B.; Xu, C.; Tan, X. S.; Peng, H.; He, H. W. Org
Biomol Chem 2012, 10, 1680.
[17] Gao, L.; Deng, X. Y.; Tan, X. S.; Long, Q. W.; Peng, H.; He,
H. W. Phosphorus, Sulfur Silicon Relat Elem 2013, 188, 989.
(diameter = 9.0 cm), and 10 rape seeds were placed on the filter
paper after soaking in water for 6 h. The Petri dishes were kept
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet