Synthesis and biological activity of 1-(Substituted phenoxyacetoxy)- 1-(pyridin-2-yl or thien-2-yl)methylphosphonates

Article abstract of DOI:10.1002/jhet.1944

A series of novel O,O-dimethyl 1-(substituted phenoxyacetoxy)-1-(pyridin-2-yl or thien-2-yl)methylphosphonates 6a-n and 7a-d 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 6a, 6c, 6l, 6m, and 7d possess 90-100% inhibition against most of the tested plants at the dosage of 1500 g ai/ha, whereas the title compounds 6b, 6g-h and 6n possess 92-100% inhibition against Fusarium oxysporum, Phyricularia grisea, Botrytis cinereapers, Gibberella zeae, Sclerotinia sclerotiorum, and Cercospora beticola at the concentration of 50mg/L.

Full text of DOI:10.1002/jhet.1944

January 2015
Synthesis and Biological Activity of 1-(Substituted phenoxyacetoxy)-
1-(pyridin-2-yl or thien-2-yl)methylphosphonates
173
*
*
Tao Wang, Wei 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: penghao@mail.ccnu.edu.cn; he1208@mail.ccnu.edu.cn
Received August 7, 2012
*
DOI 10.1002/jhet.1944
Published online 19 May 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel O,O-dimethyl 1-(substituted phenoxyacetoxy)-1-(pyridin-2-yl or thien-2-yl)methylphosphonates
1
6a–n and 7a–d 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 6a, 6c, 6l, 6m, and 7d
possess 90–100% inhibition against most of the tested plants at the dosage of 1500g ai/ha, whereas the title
compounds 6b, 6g–h and 6n possess 92–100% inhibition against Fusarium oxysporum, Phyricularia grisea,
Botrytis cinereapers, Gibberella zeae, Sclerotinia sclerotiorum, and Cercospora beticola at the concentration
of 50 mg/L.
J. Heterocyclic Chem., 52, 173 (2015).
INTRODUCTION
RESULTS AND DISCUSSION
The application of agrochemicals to protect vegetable and
cereal crops is a virtual and convenient approach for modern
agriculture. This has provided healthy crops and increased
yields as well as economic benefits for decades. The main
purpose of the research for agrochemicals is to develop novel
active compounds with lower application doses, high selec-
tivity, and benign environment [1,2]. Substituted pyridine
and thiophene derivatives, as an important class of agro-
chemicals, 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 [3–12].
On the other hand, a-substituted alkylphosphonate deri-
vatives have received considerable attention in medicine
and pesticide chemistry because of their biological activi-
ties over the past two decades [13–17]. Especially, in our
previous work, a series of 1-(substituted phenoxyacetoxy)
alkylphosphonates, as potent pyruvate dehydrogenase
complex inhibitors, were synthesized and showed notable
herbicidal activities [18–23]. However, our previous work
was not devoted to the synthesis of heterocycle-containing
1-(substituted phenoxyacetoxy)alkylphosphonates. Hence,
as part of our ongoing work aimed at searching for new
herbicidal and fungicidal compounds, we thought that the
introduction of pyridinyl and thienyl groups into the parent
structure may result in the improvement of bioactivity.
Herein, we report the synthesis and biological activities of
the phosphonates 6 and 7 (Scheme 1).
The title compounds 6a–n and 7a–d were prepared by
condensation of intermediates 2a–b with substituted phenox-
yacetyl chlorides 5 in the presence of triethylamine as a base
in chloroform (Scheme 1). The intermediates 2a–b were pre-
pared according to the reported methods [23–26]. The substi-
tuted phenoxyacetic acids 4 could be easily synthesized
starting from the corresponding substituted phenols and ethyl
2-bromoacetate in good yields.
The structures of 6a–n and 7a–d were characterized by
1H NMR, IR, MS, and elemental analysis. The proton
signal corresponding to the two methoxy groups (–OCH3) at-
tached with phosphorus appears as two doublet at d
3.68 Æ 0.04 and 3.81Æ 0.04, respectively. The differentia-
tion of the chemical shifts of the two methyl hydrogens due
to the low rate of environmental exchange caused by the
slow rotation of the P–C bond, and the magnetic nucleus
phosphorus makes the signal of both methyls split into a
doublet. In 7a–d, the signal corresponding to the methylene
group (–CH2–) flanked by the phenoxy group, and carbonyl
group appears as a quartet, the outside peaks smaller in size,
which belongs to the AB system with the difference in chem-
ical shift between the two mutually coupled protons A and B.
However, at the extreme, when A and B have exactly the
same chemical shift, the outside peaks disappear, and the in-
side peaks merge into a singlet, exemplified by 6a–n series.
The corresponding IR spectrum revealed normal absorption
bands at ~1760 (C═O) and ~3050 (Ar–H)cmÀ1. The EI
© 2014 HeteroCorporation

174
T. Wang, W. Wang, H. Peng, and H. He
Vol 52
mass spectra of the title compounds 6 and 7 revealed the ex-
istence of the molecular ion peaks, which were in good
accordance with the given structures of products.
(rape) and Echinochloa crusgalli (barnyard grass) at the
concentration of 100 and 10 mg/L using the known
procedure [23]. And 2,4-dichlorophenoxy acetic acid (2,
4-D), a commercially available herbicide, was selected as a
positive control. As shown in Table 1, 6a–6c, 6l–6m, 7a,
and 7d displayed notable herbicidal activity against the
tested plants, with more than 90% 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, the compounds 6d–6i showed 75–89%
inhibitory rate against the root of E. crusgalli at the dosage
of 10mg/L, but only 4–56% inhibitory rate against the
stem of E. crusgalli at the same dosage. 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 2,4-Cl2,
2-CH3-4-Cl, 2-Cl-4-F, and 3-CF3 as X and Y (6a–b, 6l–m,
7a, and 7d) show higher inhibitory rate (>90%) against the
root of the tested plants at the concentration of 10mg/L.
On the basis of the preliminary bioassays, 6a–g, 6l–n and
7a–d were selected for further bioassay for pre-emergence
and post-emergence herbicidal activity on B. napus (rape),
Amaranthus mangostanus (amaranth), Medicago sativa
(lucerne), E. crusgalli (barnyard grass), and Digitaria
sanguinalis (crabgrass). As shown in Table 2, it was found
that the title compounds 6a, 6l, 6m and 7d showed much bet-
ter activity than the other compounds, which is agreement
Biological activities
Herbicidal activity. The preliminary herbicidal activity
of 6a–n and 7a–d was evaluated against Brassica napus
Scheme 1. Synthetic route of compounds 6a–n and 7a–d.
Table 1
Structure and herbicidal activity of compounds 6 and 7.
Relative inhibition (stem%/root%)
aEC
aBN
Compound
X
Y
100 mg/L
10 mg/L
100 mg/L
10 mg/L
6a
6b
6c
6d
6e
2-Cl
3-CF3
4-Cl
4-F
2-Cl
3-CH3
2-Cl
2-Cl
2-F
4-Cl
H
H
98/100
80/96
95/97
90/95
70/86
75/83
78/80
86/94
39/92
13/94
22/92
91/100
52/100
13/100
88/95
70/80
20/94
92/100
34/98
95/100
51/90
90/90
48/85
40/75
30/75
40/80
56/89
4/81
22/64
22/75
81/100
48/100
61/89
61/93
31/70
25/65
61/95
33/98
100/100
90/95
96/98
90/97
89/93
85/97
88/95
83/99
57/93
95/99
76/97
100/100
100/100
97/99
92/95
90/95
90/99
100/100
94/100
95/99
90/95
90/95
88/88
79/80
80/80
82/85
14/68
22/62
49/87
5/50
89/99
92/100
43/83
90/91
85/88
40/83
90/99
94/99
H
5-CH3
4-Cl
3-Cl
6-Cl
H
4-F
H
4-F
4-Cl
H
6f
6g
6h
6i
6j
6k
6l
6m
6n
7a
7b
7c
2-F
3-F
2-Cl
2-CH3
4-CF3
3-CF3
3-CH3
2-F
H
4-Cl
H
7d
2,4-D
2-Cl
4-F
aEC for Echinochloa crusgalli; BN for Brassica napus.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2015
Synthesis and Biological Activity of 1-(Substituted phenoxyacetoxy)-1-(pyridin-2-yl or
thien-2-yl)methylphosphonates
175
Table 2
The herbicidal activity of compounds 6 and 7 (1500 g ai/ha).
aBN
Pre
89
84
90
81
6
aAM
aMS
aEC
aDS
Compound
X
Y
Post
Pre
Post
Pre
Post
Pre
Post
Pre
Post
6a
6b
6c
6d
6e
6f
6g
6l
6m
6n
7a
7b
7c
2-Cl
3-CF3
4-Cl
4-F
2-Cl
3-CH3
2-Cl
2-Cl
2-CH3
4-CF3
3-CF3
3-CH3
2-F
4-Cl
H
76
63
60
79
43
50
19
90
81
69
72
45
10
100
94
93
51
69
51
9
66
22
96
83
50
62
66
9
90
45
100
50
21
44
52
95
100
41
54
53
94
49
82
46
3
76
26
94
88
40
57
88
0
41
91
41
58
29
41
25
90
47
56
61
34
21
96
91
87
31
79
30
11
66
19
80
89
20
29
48
4
42
15
49
24
52
22
0
30
46
15
0
98
68
92
82
11
73
16
85
92
40
62
62
21
91
70
39
22
59
31
37
55
4
25
39
25
41
14
19
45
92
H
H
5-CH3
4-Cl
3-Cl
4-F
4-Cl
H
59
0
95
95
60
54
63
18
97
93
H
4-Cl
H
4-F
5
0
39
95
0
100
99
7d
2,4-D
2-Cl
100
94
100
92
83
73
aBN for Brassica napus; AM for Amaranthus mangostanus; MS for Medicago sativa; EC for Echinochloa crusgalli; DS for Digitaria sanguinalis.
with the results in the preliminary bioassays. And the
title compounds 6a, 6l, 6m, and 7d exhibited notable pre-
emergence inhibitory effects against all the weed species,
with more than 80% inhibitory rate. Especially, 6l and 7d
showed excellent herbicidal activity against the dicotyledon-
ous weeds, such as B. napus, A. mangostanus and M. sativa,
with more than 90% inhibitory for pre-emergence and post-
emergence at the dosage of 1500 g ai/ha, which is compara-
ble with 2,4-D. However, 6l and 7d showed weaker
inhibitory activity in comparison with 2,4-D for post-
emergence against the monocotyledonous plants, such as E.
crusgalli and D. sanguinalis. These findings suggested that
the compounds 6l and 7d had a higher level of selectivity
between the monocotyledonous and dicotyledonous plants,
enhanced by introducing 3-CF3 or 4-CF3 on the phenoxy
ring. In the case of single halo substituted derivatives like
6i and 6k, with halo substitution at ortho and meta position
in phenoxy ring showed better activity compared with that
substituted at para position (6c and 6d). When the X and Y
groups were kept constant, compounds 6b, 6f, 6i, and 6l
exhibited much higher fungicidal activity than compounds
7a–d, indicating that pyridinyl group introduced to the
parent structure was more beneficial for the improvement
of fungicidal activity than the thienyl group.
In conclusion, a series of novel O,O-dimethyl 1-(substi-
tuted phenoxyacetoxy)-1-(pyridn-2-yl or thien-2-yl) methyl-
phosphonates 6a–n and 7a–d were designed and
synthesized. The results of preliminary bioassays showed
that most of the title compounds exhibited moderate to good
herbicidal activity at the dosage of 1500 g ai/ha. In addition,
the compounds 6b, 6g, 6h, and 6n also possessed high
fungicidal activity and broad spectrum against all the tested
fungi with 90–100% inhibition effect. These results indicated
that the title compounds 6 and 7 could be modified and used
as lead compounds for further study.
especially for post-emergence.
Fungicidal activity. The fungicidal activities of 6a–n and
7a–d 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 3, most of compounds display moderate to good
fungicidal activity against the aforementioned six fungi.
For example, the compounds 6b, 6g, 6h, and 6n possessed
high fungicidal activity and broad spectrum against all the
target fungi with 90–100% inhibition effect. It was found
that the X and Y groups on the phenoxy ring had great
impact on the fungicidal activity. The 2,3-Cl2 and 2,6-Cl2
di-substitution on the phenoxy ring was the most
promotive, followed by 2-Cl-5-CH3, 3-CH3-4-Cl, 2,4-F2,
and 2-Cl-4-F. The fungicidal activity could also be greatly
EXPERIMENTAL
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
silica gel (200–300 mesh). Melting points (mp) were measured on a
X-4 melting point apparatus (Beijing, China) and were uncorrected.
IR spectra were recorded as KBr pellets on a Perkin-Elmer Fourier
transform infrared spectrophotometer (USA). 1H NMR was recorded
on Varian XL-300 spectrometer at 300 MHz or Varian XL-400 spec-
trometer (Salt Lake City, USA) at 400 MHz using tetramethylsilane
as internal standard (solvent CDCl3). Chemical shifts (d) are given
in parts per million, coupling constants (J) are in Hertz, and
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

176
T. Wang, W. Wang, H. Peng, and H. He
Vol 52
Table 3
Fungicidal activity of compounds 6 and 7.
50 mg/L
aBC
Compound
X
Y
aFO
22
aPG
aGZ
aSS
aCB
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
7a
7b
7c
7d
2-Cl
3-CF3
4-Cl
4-F
2-Cl
3-CH3
2-Cl
2-Cl
2-F
2-F
4-Cl
H
38
96
46
65
97
64
100
57
84
99
100
100
100
99
100
100
100
91
53
100
26
53
79
70
95
98
91
88
84
95
51
97
71
56
68
65
74
100
72
26
100
37
55
84
98
94
100
94
100
94
100
39
100
67
56
59
93
44
33
79
96
96
92
58
92
92
88
58
96
59
52
70
48
H
H
99
5-CH3
4-Cl
3-Cl
6-Cl
H
4-F
H
4-F
4-Cl
H
100
100
100
100
100
93
100
100
95
100
98
98
97
98
97
100
100
94
97
97
100
71
100
62
69
69
3-F
2-Cl
2-CH3
4-CF3
3-CF3
3-CH3
2-F
100
98
98
95
95
H
4-Cl
H
4-F
2-Cl
42
44
aFO for Fusarium oxysporum; PG for Phyricularia grisea; BC for Botrytis cinereapers; GZ for Gibberella zeae; SS for Sclerotinia sclerotiorum; CB for
Cercospora beticola.
105–106ꢀC; IR (KBr, cmÀ1): n 3056, 2963, 2852, 1766,
multiplicities are implicated by s (singlet), d (doublet), t (triplet), q
(quartet), and m (multiplet). MS spectra were analyzed on a Finnigan
1591, 1478, 1451, 1265, 1190, 1027, 926, 755. 1H NMR
(300 MHz, CDCl3) d 3.72 (d, 3H, –OCH3, J = 9.9 Hz), 3.80
(d, 3H, –OCH3, J = 9.9 Hz), 4.88 (s, 2H, –OCH2CO–), 6.36
(d, 1H, –OCHP, J = 13.8 Hz), 6.81 (d, 1H, 6-phenyl-H,
J = 8.8 Hz), 7.14 (dd, 1H, 5-phenyl-H, J = 2.5 Hz, J = 2.5 Hz),
7.27 (d, 1H, 5-pyrinyl-H, J = 8.3 Hz), 7.38 (d, 1H, 3-phenyl-H,
J = 2.5 Hz), 7.45 (d, 1H, 3-pyrinyl-H, J = 7.7 Hz), 7.69–7.75
(m, 1H, 4-pyrinyl-H), 8.63 (s, 1H, 6-pyrinyl-H); 31P NMR
(120 MHz CDCl3): d 8.5; EI-MS m/z (%): 419 (M+, 13.91),
220 (65.58), 216 (36.89), 203 (7.56), 200 (60.25), 175 (60.80),
162 (100), 146 (27.15), 109 (50.31), 94 (6.68), 93 (40.49), 79
(18.54). Anal. Calcd for C16H16Cl2NO6P: C, 45.74; H, 3.84;
N, 3.33. Found: C, 45.97; H, 3.79; N, 2.94.
O,O-Dimethyl 1-[(3-trifluoromethylphenoxy)acetoxy]-1-
(pyridin-2-yl)methylphosphonate (6b). White solid; yield, 71%;
mp, 79–80ꢀC; IR (KBr, cmÀ1): n 3076, 2964, 2852, 1784,
1608, 1495, 1441, 1248, 1178, 1030, 938, 754. 1H NMR
(300 MHz, CDCl3) d 3.65 (d, 3H, –OCH3, J = 11.3 Hz), 3.80
(d, 3H, –OCH3, J = 11.3 Hz), 4.87 (s, 2H, –OCH2CO–), 6.38
(d, 1H, –OCHP, J = 13.8 Hz), 7.08–7.46 (m, 6H, 2, 4, 5 and
6-phenyl-H, 3 and 5- pyrinyl-H), 7.71–7.72 (m, 1H, 4-pyrinyl-H),
8.61–8.64 (m, 1H, 6-pyrinyl-H); EI-MS m/z (%): 419 (M+ +1,
16.56), 244 (72.49), 216 (12.52), 201 (27.18), 175 (56.34), 145
(100), 127 (23.75), 109 (61.20), 94 (8.12), 93 (68.93), 79 (50.46),
75 (11.22), 63 (15.56). Anal. Calcd for C17H17F3NO6P: C, 48.70;
H, 4.09; N, 3.34. Found: C, 48.61; H, 4.04; N, 3.39.
TRACE spectrometer (Ramsey, USA) and API2000LC/MS
(Framingham, USA). Elemental analyses were performed by a Vario
EL III elemental analyzer (Hanau, Germany).
General procedure for the synthesis of 2a–b. O,O-Dimethyl
1-hydroxy-1-(pyridin-2-yl)methylphosphonate 2a and 1-hydroxy-
1-(thien-2-yl)methylphosphonate 2b could be prepared by the
reaction of dimethyl phosphite 1 and pyridin-2-carbaldehyde or
thien-2-carbaldehyde in chloroform using triethylamine as catalyst
in yields of 80–90% according to literatures [23–26].
General procedure for the synthesis of 4 and 5.
The
substituted phenoxyacetic acid 4 was synthesized by a standard
method [23,27]. A mixture containing substituted phenoxyacetyl
acid 4 (4.0 mmol) and thionyl chloride (3 mL) was added into a
25 mL flask and refluxed for 5–6 h. Excess thionyl chloride was
evaporated off under reduced pressure, and a light yellow oil 5
was obtained with a yield of 85–90%.
General procedure for the synthesis of 6a–n and 7a–d.
A
solution of substituted phenoxyacetyl chlorides 5 (3.3 mmol) in
chloroform (15 mL) was added to a stirred mixture of 2a or 2b
(3 mmol) and triethylamine (3.3 mmol) in chloroform (20 mL) at
0–5ꢀC. The resultant mixture was stirred for 3–5 h at room
temperature and then for 1–2 h at 40ꢀC. The chloroform 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 6a–n and 7a–d. Their
O,O-Dimethyl1-[(4-chlorophenoxy)acetoxy]-1-(pyridin-2-yl)
methylphosphonate (6c). White solid; yield, 76%; mp, 124–125ꢀC;
IR (KBr, cmÀ1): n 3069, 2955, 2850, 1777, 1589, 1495, 1447,
1255, 1172, 1038, 945, 772. 1H NMR (300 MHz, CDCl3) d
3.65 (d, 3H, –OCH3, J= 10.7 Hz), 3.80 (d, 3H, –OCH3, J= 10.7 Hz),
4.80 (s, 2H, –OCH2CO–), 6.37 (d, 1H, –OCHP, J = 13.8 Hz),
6.85 (dd, 2H, 2 and 6-phenyl-H, J = 2.5 Hz, J = 6.8 Hz), 7.21
(dd, 2H, 3 and 5-phenyl-H, J = 2.5 Hz, J = 6.8 Hz), 7.27 (d, 1H,
1
structures were confirmed by H NMR, IR, MS, and elemental
analysis. And the physicochemical properties and spectroscopic
data for compounds 6a–n and 7a–d are as follows.
O,O-Dimethyl 1-[(2,4-dichlorophenoxy)acetoxy]-1-(pyridin-2-
yl)methylphosphonate (6a). White solid; yield, 88%; mp,
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Synthesis and Biological Activity of 1-(Substituted phenoxyacetoxy)-1-(pyridin-2-yl or
thien-2-yl)methylphosphonates
177
5-pyrinyl-H, J = 8.4 Hz), 7.45 (d, 1H, 3-pyrinyl-H, J = 7.9 Hz),
7.68–7.75 (m, 1H, 4-pyrinyl-H), 8.62 (d, 1H, 6-pyrinyl-H,
J = 4.8 Hz); EI-MS m/z (%): 385 (M+ + 1, 7.52), 258 (16.56),
244 (61.27), 216 (7.05), 201 (25.40), 140 (37.78), 127 (5.05),
109 (73.14), 94 (7.19), 93 (100), 79 (52.33), 75 (34.88), 63
(20.18). Anal. Calcd for C16H17ClNO6P: C, 49.82; H, 4.44; N,
3.63. Found: C, 49.90; H, 4.21; N, 3.66.
(26.52), 109 (67.98), 94 (6.31), 93 (71.43), 79 (41.83), 75 (13.80),
63 (19.00); Anal. Calcd for C16H16Cl2NO6P: C, 45.47; H, 3.84;
N, 3.33. Found: C, 45.80; H, 3.63; N, 3.38.
O,O-Dimethyl 1-[(2,6-dichlorophenoxy)acetoxy]-1-(pyridin-2-
yl)methylphosphonate (6h).
White solid; yield, 68%;
mp,125–126ꢀC; IR (KBr, cmÀ1): n 3074, 2947, 2849, 1738,
1630, 1512, 1458, 1222, 1156, 1048, 939, 785; 1H NMR
(400 MHz, CDCl3) d 3.72 (d, 3H, –OCH3, J = 10.8 Hz), 3.81
(d, 3H, –OCH3, J = 10.8 Hz), 4.92 (s, 2H, –OCH2CO–), 6.37
(d, 1H, –OCHP, J = 14.0 Hz), 6.78 (dd, 1H, 4-phenyl-H,
J = 2.8 Hz, J = 2.8 Hz), 7.11–7.13 (m, 2H, 3 and 5-phenyl-H),
7.28–7.29 (m, 1H, 5-pyrinyl-H), 7.45–7.47 (m, 1H, 3-pyrinyl-H),
7.72–7.73 (m, 1H, 4-pyrinyl-H), 8.63 (d, 1H, 6-pyrinyl-H,
J = 4.4 Hz); EI-MS m/z (%): 419 (M++1, 1.05), 258 (23.60), 244
(62.50), 216 (7.49), 201 (16.83), 200 (5.30), 182 (4.64), 175
(27.45), 162 (16.04), 145 (34.46), 109 (100), 94 (7.74), 93
(70.77), 79 (58.37), 75 (22.27), 63 (38.56); Anal. Calcd for
C16H16Cl2NO6P: C, 45.47; H, 3.84; N, 3.33. Found: C, 45.82; H,
3.65; N, 3.38.
O,O-Dimethyl 1-[(4-fluorophenoxy)acetoxy]-1-(pyridin-2-yl)
methylphosphonate (6d).
Yellow solid; yield, 67%; mp,
68–70ꢀC; IR (KBr, cmÀ1): n 3059, 2959, 2857, 1767, 1630,
1507, 1440, 1254, 1179, 1050, 933, 775. 1H NMR (300 MHz,
CDCl3) d 3.65 (d, 3H, –OCH3, J = 10.7Hz), 3.80 (d, 3H, –OCH3,
J = 10.7 Hz), 4.79 (s, 2H, –OCH2CO–), 6.37 (d, 1H, –OCHP,
J = 13.8 Hz), 6.84–6.88 (m, 2H, 2 and 6-phenyl-H), 6.89–6.99
(m, 2H, 3 and 5-phenyl-H), 7.25–7.30 (m, 1H, 5-pyrinyl-H), 7.45
(d, 1H, 3-pyrinyl-H, J = 7.9 Hz), 7.68–7.72 (m, 1H, 4-pyrinyl-H),
8.60–8.63 (m, 1H, 6-pyrinyl-H); EI-MS m/z (%): 369 (M+ +1,
1.10), 244 (7.12), 216 (1.23), 201 (3.36), 170 (52.30), 148 (2.27),
125 (45.29), 109 (8.43), 95 (100), 93 (20.33), 79 (20.25), 75
(31.95), 63 (17.03). Anal. Calcd for C16H17FNO6P: C, 52.04; H,
4.64; N, 3.79. Found: C, 51.88; H, 4.61; N, 3.68.
O,O-Dimethyl 1-[(2-fluorophenoxy)acetoxy]-1-(pyridin-2-yl)
methylphosphonate (6i).
Yellow oil; yield, 63%; n2D0 1.5062;
IR (KBr, cmÀ1): n 3070, 2959, 2855, 1771, 1591, 1505, 1437,
O,O-Dimethyl 1-[(2-chloro-5-methylphenoxy)acetoxy]-1-
(pyridin-2-yl)methylphosphonate (6e). White solid; yield, 78%;
mp, 76–77ꢀC; IR (KBr, cmÀ1): n 3049, 2952, 2853, 1754, 1629,
1493, 1441, 1222, 1182, 1054, 936, 778. 1H NMR (300 MHz,
CDCl3) d 2.27 (s, 3H, CH3Ph), 3.72 (d, 3H, –OCH3, J = 9.0 Hz),
3.80 (d, 3H, –OCH3, J = 9.0 Hz), 4.88 (s, 2H, –OCH2CO–), 6.38
(d, 1H, –OCHP, J= 13.5 Hz), 6.67 (d, 1H, 6-phenyl-H, J=1.2Hz),
6.74–6.77 (m, 1H, 4-phenyl-H), 7.23–7.30 (m, 2H, 3-phenyl-H,
5-pyrinyl-H), 7.44 (d, 1H, 3-pyrinyl-H, J = 8.0 Hz), 7.68–7.74
(m, 1H, 4-pyrinyl-H), 8.60–8.63 (m, 1H, 6-pyrinyl-H); EI-MS
m/z (%): 399 (M+ + 1, 0.82), 216 (1.51), 200 (8.69), 183 (1.64),
155 (8.17), 125 (8.54), 109 (9.44), 95 (36.66), 93 (23.52), 79
(100), 75 (9.49), 63 (19.17). Anal. Calcd for C17H19ClNO6P: C,
1
1263, 1182, 1036, 942, 754; H NMR (400 MHz, CDCl3) d 3.72
(d, 3H, –OCH3, J = 9.6Hz), 3.81 (d, 3H, –OCH3, J = 9.6Hz), 4.82
(s, 2H, –OCH2CO–), 6.39 (d, 1H, –OCHP, J = 14.0 Hz),
6.63–6.71 (m, 3H, 3, 4 and 6-phenyl-H), 7.21–7.29 (m, 2H,
3-phenyl-H, 5-pyrinyl-H), 7.44–7.47 (m, 1H, 3-pyrinyl-H),
7.72–7.73 (m, 1H, 4-pyrinyl-H), 8.63 (d, 1H, 6-pyrinyl-H,
J = 4.4 Hz); EI-MS m/z (%): 369 (M+ + 1, 1.52), 216 (2.44), 201
(4.98), 148 (7.10), 125 (52.34), 109 (76.83), 94 (12.68), 93
(100), 79 (54.16), 75 (29.13), 63 (17.20); Anal. Calcd for
C16H17FNO6P: C, 52.04; H, 4.64; N, 3.79. Found: C, 51.89; H,
4.39; N, 3.83.
O,O-Dimethyl 1-[(2,4-difluorophenoxy)acetoxy]-1-(pyridin-
2-yl)methylphosphonate (6j).
Yellow oil; yield, 67%; nD20
51.08; H, 4.79; N, 3.50. Found: C, 50.94; H, 4.93; N, 3.25.
O,O-Dimethyl 1-[(4-chloro-5-methylphenoxy)acetoxy]-1-
1.5183; IR (KBr, cmÀ1): n 3059, 2960, 2856, 1771, 1590, 1515,
1
(pyridin-2-yl)methylphosphonate (6f). White solid; yield, 74%;
mp, 83–85ꢀC; IR (KBr, cmÀ1): n 3058, 2957, 2854, 1776, 1593,
1482, 1435, 1258, 1167, 1035, 935, 772. 1H NMR (300MHz,
CDCl3) d 2.31 (s, 3H, kCH3Ph), 3.71 (d, 3H, –OCH3, J= 10.8 Hz),
3.83 (d, 3H, –OCH3, J= 10.8 Hz), 4.79 (s, 2H, –OCH2CO–), 6.37
(d, 1H, –OCHP, J= 13.8 Hz), 6.66–6.70 (m, 1H, 6-phenyl-H), 6.79
(d, 1H, 2-phenyl-H, J = 3.1 Hz), 7.19–7.30 (m, 2H, 3-phenyl-H,
5-pyrinyl-H), 7.40–7.44 (m, 1H, 3-pyrinyl-H), 7.68–7.74
(m, 1H, 4-pyrinyl-H), 8.61–8.63 (m, 1H, 6-pyrinyl-H); EI-MS
m/z (%): 399 (M+, 33.17), 258 (41.95), 244 (99.57), 216 (17.44),
201 (47.25), 200 (20.85), 182 (10.15), 155 (38.74), 125 (75.49),
109 (81.07), 94 (10.36), 93 (100), 79 (67.15), 75 (8.30), 63
(34.44). Anal. Calcd for C17H19ClNO6P: C, 51.08; H, 4.79; N,
3.50. Found: C, 50.83; H, 4.54; N, 3.52.
1437, 1267, 1174, 1036, 965, 753; H NMR (400 MHz, CDCl3)
d 3.71 (d, 3H, –OCH3, J = 10.8 Hz), 3.80 (d, 3H, –OCH3,
J = 10.8 Hz), 4.85 (s, 2H, –OCH2CO–), 6.36 (d, 1H, –OCHP,
J = 13.6 Hz), 6.76–6.98 (m, 3H, 3, 5 and 6-phenyl-H), 7.28–7.29
(m, 1H, 5-pyrinyl-H), 7.45–7.48 (m, 1H, 3-pyrinyl-H), 7.70–7.75
(m, 1H, 4-pyrinyl-H), 8.61 (d, 1H, 6-pyrinyl-H, J = 4.8 Hz);
EI-MS m/z (%): 387 (M+ + 1, 5.12), 244 (28.45), 201 (10.73),
143 (59.47), 113 (46.76), 109 (69.39), 94 (10.67), 93 (100), 79
(51.89), 75 (6.92), 63 (31.99); Anal. Calcd for C16H16F2NO6P: C,
49.62; H, 4.16; N, 3.62. Found: C, 49.67; H, 4.18; N, 3.53.
O,O-Dimethyl 1-[(3-fluorophenoxy)acetoxy]-1-(pyridin-2-yl)
methylphosphonate (6k).
Yellow solid; yield, 66%;
mp,79–80ꢀC; IR (KBr, cmÀ1): n 3072, 2962, 2850, 1774, 1591,
1493, 1450, 1254, 1188, 1054, 940, 771; 1H NMR (400MHz,
CDCl3) d 3.71 (d, 3H, –OCH3, J =10.4 Hz,), 3.79 (d, 3H, –OCH3,
J = 10.4Hz,), 4.81 (s, 2H, –OCH2CO–), 6.39 (d, 1H, –OCHP,
J = 13.6Hz), 6.63–6.71 (m, 3H, 2, 4 and 6-phenyl-H), 7.21–7.29
(m, 2H, 5-phenyl-H, 5-pyrinyl-H), 7.44–7.47 (m, 1H, 3-pyrinyl-H),
7.71–7.72 (m, 1H, 4-pyrinyl-H), 8.63 (d, 1H, 6-pyrinyl-H,
J= 4.8 Hz); EI-MS m/z (%): 369 (M+ + 1, 4.64), 258 (10.51), 244
(88.45), 216 (11.62), 201 (24.99), 170 (11.29), 148 (8.17), 125
(54.51), 109 (59.36), 95 (100), 93 (80.93), 79 (49.99), 75 (31.87),
63 (14.67); Anal. Calcd for C16H17FNO6P: C, 52.04; H, 4.64; N,
3.79. Found: C, 51.66; H, 4.40; N, 3.79.
O,O-Dimethyl 1-[(2,3-dichlorophenoxy)acetoxy]-1-(pyridin-2-
yl)methylphosphonate (6g). White solid; yield, 66%; mp, 115–
116ꢀC; IR (KBr, cmÀ1): n 3077, 2957, 2852, 1779, 1586, 1468,
1
1443, 1252, 1173, 1053, 946, 773; H NMR (400MHz, CDCl3)
d
3.71 (d, 3H, –OCH3, J = 11.2 Hz), 3.80 (d, 3H, –OCH3,
J = 11.2 Hz), 4.92 (s, 2H, –OCH2CO–), 6.37 (d, 1H, –OCHP,
J = 14.0 Hz), 6.78 (dd, 1H, 6-phenyl-H, J = 2.4Hz, J = 2.4 Hz),
7.11–7.13 (m, 2H, 4 and 5-phenyl-H), 7.28–7.29 (m, 1H,
5-pyrinyl-H), 7.45–7.48 (m, 1H, 3-pyrinyl-H), 7.70–7.74 (m, 1H,
4-pyrinyl-H), 8.63 (d, 1H, 6-pyrinyl-H, J = 4.4Hz); EI-MS m/z
(%): 419 (M++1, 5.85), 258 (18.10), 244 (100), 216 (12.35), 201
(18.31), 200 (7.69), 182 (4.07), 175 (30.65), 162 (5.65), 145
O,O-Dimethyl 1-[(2-chloro-4-fluorophenoxy)acetoxy]-1-
(pyridin-2-yl)methylphosphonate (6l).
White solid; yield, 74%;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

178
T. Wang, W. Wang, H. Peng, and H. He
Vol 52
mp,124–126ꢀC; IR (KBr, cmÀ1): n 3073, 2963, 2851, 1775,
1592, 1493, 1449, 1254, 1188, 1054, 967, 771; 1H NMR
(400 MHz, CDCl3) d 3.71 (d, 3H, –OCH3, J = 11.8 Hz), 3.81
(d, 3H, –OCH3, J = 11.8 Hz), 4.92 (s, 2H, –OCH2CO–), 6.36
(dd, 1H, –OCHP, J = 1.6 Hz, J = 1.6 Hz), 6.81 (dd, 1H,
6-phenyl-H, J=1.2Hz, J= 1.2 Hz), 7.13–7.16 (m, 1H, 5-phenyl-H),
7.29 (s, 1H, 5-pyrinyl-H), 7.39 (s, 1H, 3-phenyl-H), 7.44–7.46
(m, 1H, 3-pyrinyl-H), 7.72 (t, 1H, 4-pyrinyl-H, J = 7.6 Hz),
8.62 (s, 1H, 6-pyrinyl-H); EI-MS m/z (%): 403 (M+, 0.65), 204
(17.61), 159 (27.85), 146 (69.10), 129 (44.29), 109 (18.59), 94
(23.37), 93 (23.49), 79 (2.73), 75 (17.70), 63 (19.17); Anal.
Calcd for C16H16ClFNO6P: C, 47.60; H, 3.99; N, 3.47. Found:
OCH2O, J= 16.5 Hz), 6.53 (d, 1H, –OCHP, J= 13.6 Hz), 6.62–6.66
(m, 1H, 6-phenyl-H), 6.74 (d, 1H, 2-phenyl-H, J = 2.7 Hz),
7.00–7.04 (m, 1H, 3-thienyl-H), 7.20 (d, 1H, 3-phenyl-H,
J = 8.7 Hz), 7.26–7.29 (m, 1H, 4-thienyl-H), 7.37–7.39 (m, 1H,
5-thienyl-H); EI-MS m/z (%): 404 (M+, 13.21), 369 (25.58),
325 (60.90), 250 (25.94), 219 (45.97), 205 (100), 200 (44.18),
155 (86.48), 142 (37.21), 125 (74.54), 109 (60.10), 94 (17.03),
93 (99.00), 75 (8.28), 63 (49.59), 44 (22.09); Anal. Calcd for
C16H18ClO6PS: C, 47.47; H, 4.48; Found: C, 47.19; H, 4.46.
O,O-Dimethyl 1-[(2-fluorophenoxy)acetoxy]-1-(thien-2-yl)
methylphosphonate (7c). White solid; yield, 72%; mp, 73–74ꢀC;
IR (KBr, cmÀ1): n 3082, 2954, 2846, 1763, 1613, 1510, 1433,
1
1261, 1180, 1025, 929, 756; H NMR (400 MHz, CDCl3) d 3.66
C, 47.29; H, 4.26; N, 3.30.
O,O-Dimethyl 1-[(4-chloro-2-methylphenoxy)acetoxy]-1-
(d, 3H, –OCH3, J= 10.8 Hz), 3.78 (d, 3H, –OCH3, J= 10.8 Hz),
4.73, 4.79 (q, AB system, 2H, OCH2O, J= 16.5 Hz), 6.51 (d, 1H,
–OCHP, J= 13.8 Hz), 6.82–7.10 (m, 5H, 3, 4, 5 and 6-phenyl-H,
3-thienyl-H), 7.23–7.24 (m, 1H, 4-thienyl-H), 7.34 (d, 1H,
5-thienyl-H, J = 5.2 Hz); EI-MS m/z (%): 374 (M+, 27.44), 221
(46.69), 205 (54.49), 170 (37.80), 125 (100), 112 (68.67), 109
(21.14), 94 (6.10), 93 (98.49), 75 (17.29), 63 (14.08), 44
(13.56); Anal. Calcd for C15H16FO6PS: C, 48.13; H, 4.31;
(pyridin-2-yl)methylphosphonate (6m). White solid; yield, 77%;
mp, 75–77ꢀC; IR (KBr, cmÀ1): n 3013, 2963, 2850, 1767, 1592,
1493, 1432, 1264, 1177, 1047, 939, 755; 1H NMR (400 MHz,
CDCl3) d 2.26 (s, 3H, CH3Ph), 3.71 (d, 3H, –OCH3, J= 10.4 Hz),
3.80 (d, 3H, –OCH3, J= 10.4 Hz), 4.82 (s, 2H, –OCH2CO–), 6.37
(d, 1H, –OCHP, J= 14.0 Hz), 6.63 (d, 1H, 6-phenyl-H, J=8.8Hz),
7.05 (d, 1H, 5-phenyl-H, J = 8.4 Hz), 7.13 (s, 1H, 5-pyrinyl-H),
7.28 (s, 1H, 3-phenyl-H), 7.39–7.41 (m, 1H, 3-pyrinyl-H), 7.72
(t, 1H, 4-pyrinyl-H, J = 7.6 Hz), 8.62 (d, 1H, 6-pyrinyl-H,
J = 4.4 Hz); EI-MS m/z (%): 399 (M+ + 1, 31.22), 216 (21.72),
201 (77.68), 182 (5.68), 155 (35.00), 141 (43.45), 125 (72.49),
109 (78.91), 108 (100), 94 (12.15), 93 (98.32), 79 (74.73), 75
(8.92), 63 (31.67); Anal. Calcd for C17H19ClNO6P: C, 51.08;
H, 4.79; N, 3.50. Found: C, 50.78; H, 4.99; N, 3.28.
O,O-Dimethyl 1-[(4-trifluoromethylphenoxy)acetoxy]-1-
(pyridin-2-yl)methylphosphonate (6n). White solid; yield, 68%;
mp, 73–74ꢀC; IR (KBr, cmÀ1): n 3081, 2964, 2859, 1784, 1593,
1494, 1441, 1248, 1177, 1052, 940, 754; 1H NMR (400 MHz,
CDCl3) d 3.71 (d, 3H, –OCH3, J = 11.2Hz), 3.80 (d, 3H, –OCH3,
J = 11.2 Hz), 4.88 (s, 2H, –OCH2CO–), 6.38 (d, 1H, –OCHP,
J = 13.6 Hz), 7.09–7.47 (m, 6H, 2, 3, 5 and 6-phenyl-H, 3 and
5-pyrinyl-H), 7.73 (t, 1H, 4-pyrinyl-H, J = 7.6 Hz), 8.64 (d, 1H,
6-pyrinyl-H, J = 4.4 Hz); EI-MS m/z (%): 419(M+ + 1, 0.71),
244 (19.55), 220 (16.39), 216 (4.54), 201 (27.32), 175 (41.83),
162 (25.40), 145 (100), 127 (27.99), 109 (34.71), 94 (8.17), 93
(32.41), 79 (49.51), 75 (33.08), 63 (36.80); Anal. Calcd for
C17H17F3NO6P: C, 48.70; H, 4.09; N, 3.34. Found: C, 48.42;
Found: C, 48.32; H, 4.16.
O,O-Dimethyl 1-[(2-chloro-4-fluorophenoxy)acetoxy]-1-
(thien-2-yl)methylphosphonate (7d).
Yellow solid; yield,
78%; mp, 68–70ꢀC; IR (KBr, cmÀ1): n 3086, 2962, 2857,
1
1762, 1603, 1494, 1450, 1249, 1188, 1026, 938, 746; H NMR
(400MHz, CDCl3) d 3.70 (d, 3H, –OCH3, J = 10.8Hz), 3.81
(d, 3H, –OCH3, J= 10.8 Hz), 4.74, 4.78 (q, AB system, 2H,
OCH2O, J= 16.5 Hz), 6.54 (d, 1H, –OCHP, J= 13.6 Hz), 6.80–6.82
(m, 1H, 6-phenyl-H), 6.87–6.88 (m, 1H, 3-thienyl-H), 7.01–7.03
(m, 1H, 5-phenyl-H), 7.12–7.39 (m, 3H, 4 and 5-thienyl-H,
3-phenyl-H,); EI-MS m/z (%): 408 (M+, 29.31), 271 (8.29), 221
(34.20), 205 (98.18), 159 (89.16), 129 (74.48), 111 (100), 93
(95.69), 79 (39.73), 75 (9.63), 63 (21.54), 45 (20.46); Anal. Calcd
for C15H15ClFO6PS: C, 44.07; H, 3.70; Found: C, 43.90; H, 3.56.
Biological activity testing.
The preliminary herbicidal
activity of title compounds 6a–n and 7a–d was measured
according to the modified method described previously [12]. 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 = 5.5cm) in Petri dishes
(diameter = 9.0cm), and 10 rape seeds were placed on the filter
paper after soaking in water for 6 h. The Petri dishes were kept
at 28ꢀC for 3 days with 10h of lighting and 14h 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.
Then some of the title compounds 6 and 7 were selected for
further test against dicotyledonous weeds such as B. napus, A.
mangostanus, and M. sativa and monocotyledonous weeds such
as E. crusgalli and D. sanguinalis at the dosage of 1500 g ai/ha
according to the method described in [21,23]. Plastic pots were
packed with sandy clay loam soil and water was added up to
3 cm in depth. About 15–20 seeds of plants were sown in the soil
at a depth of 5 mm and grown at 20–25ꢀC for a few days. The
diluted solution of each compound containing acetone and Tween
80 were applied into the pots at 1500 g ai/ha. Twenty days later,
H, 4.03; N, 3.35.
O,O-Dimethyl 1-[(3-trifluoromethylphenoxy)acetoxy]-1-
(thien-2-yl)methylphosphonate (7a). Yellow solid; yield,
72%; mp, 74–75ꢀC; IR (KBr, cmÀ1): n 3083, 2926, 2855,
1
1763, 1593, 1494, 1444, 1275, 1173, 1026, 936, 724; H NMR
(300 MHz, CDCl3) d 3.68 (d, 3H, –OCH3, J = 10.7 Hz), 3.81
(d, 3H, –OCH3, J = 10.7 Hz), 4.74, 4.79 (q, AB system, 2H,
OCH2O, J= 16.5 Hz), 6.54 (d, 1H, –OCHP, J= 13.5 Hz), 7.00–7.11
(m, 3H, 6-phenyl-H, 3 and 4-thienyl-H), 7.24–7.30 (m, 2H, 2
and 4-phenyl-H), 7.36–7.42 (m, 2H, 5-thienyl-H, 5-phenyl-H);
31P NMR(120 MHz CDCl3): d 6.3; EI-MS m/z (%): 424 (M+,
10.10), 220 (26.21), 205 (19.30), 175 (100), 162 (14.19), 145
(76.58), 133 (3.44), 109 (11.00), 94 (2.55), 93 (65.31), 75
(4.58), 63 (7.41), 44 (15.86); Anal. Calcd for C16H16F3O6PS:
C, 45.29; H, 3.80; Found: C, 45.06; H, 3.91.
O,O-Dimethyl 1-[(4-chloro-5-methylphenoxy)acetoxy]-1-
(thien-2-yl)methylphosphonate (7b). Yellow solid; yield, 88%;
mp, 74–75ꢀC; IR (KBr, cmÀ1): n 3076, 2931, 2852, 1766, 1599,
1489, 1435, 1249, 1174, 1027, 928, 725; 1H NMR (300 MHz,
CDCl3) d 2.30 (s, 3H, CH3Ph), 3.68 (d, 3H, –OCH3, J = 10.7 Hz),
3.81 (d, 3H, –OCH3, J = 10.7Hz), 4.66, 4.70 (q, AB system, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2015
Synthesis and Biological Activity of 1-(Substituted phenoxyacetoxy)-1-(pyridin-2-yl or
thien-2-yl)methylphosphonates
179
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the pre-emergence, the activity was visually evaluated. At the post-
emergence, the solution was applied to the foliage of plants grown
at two or three leaves with a sprayer at the rate of 1500 g ai/ha. All
the treatments were replicated three times in a completely random-
ized design. The test plants were harvested 20 days after sowing,
and determined for fresh weight. The post-emergence herbicidal
activity against each weed was evaluated.
The fungicidal activity measurement method was adapted
from [11]. The phosphonates were dissolved in DMF (0.5–1.0 mL)
to the concentration of 1000mg/L. The solutions (1mL) were
mixed rapidly with thawed potato glucose agar culture medium
(9 mL) under 50ꢀC. The mixtures were poured into Petri dish.
After the dishes were cooled, the solidified plates were incubated
with 4-mm mycelium disk, inverted, and incubated at 28ꢀC for
48h. Distilled water was used as the blank control. Three replicates
of each test were carried out. The mycelial elongation radius (mm)
of fungi settlements was measured after 48h of culture. The growth
inhibitory rates were calculated with the following equation: I = [(C
T)/C] Â 100%. Here, I is the growth inhibitory rate (%), T is the
treatment group fungi settlement radius (mm), and C is the radius
of the blank control.
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Acknowledgments. This research was supported in part by National
Basic Research Program of China (No. 2010CB126100), the
National Key Technologies
R & D Program of China
(No.2011BAE06B03) and the National Natural Science
Foundation of China (No. 21172090). The research was
supported in part by the PCSIRT (No. IRT0953). The author is
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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