Synthesis and herbicidal activity of 2-(Substituted phenoxyacetoxy)alkyl-5, 5-dimethyl-1,3,2-dioxaphosphinan-2-one

Article abstract of DOI:10.1021/jf301829m

A series of 2-(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2- dioxaphosphinan-2-ones IIa-s were designed and synthesized on the basis of the previous work for the modification of alkylphosphonates I, and their structures were confirmed by ¹H NMR, ³¹P NMR, ¹³C NMR, IR, MS, and elemental analysis. Their herbicidal activities against seven species of weeds were evaluated in a greenhouse. A part of the title compounds such as IIa-g, IIk, IIo, and IIr exhibited significant postemergence herbicidal activity against Abutilon theophrasti, Brassica juncea, Amaranthus retroflexus, and Eclipta prostrate at a dosage of 150 g ai/ha. Structure-activity relationship analyses indicated that the introduction of a phosphorus-containing heterocyclic ring had a favorable effect on herbicidal activity, and their herbicidal activity could be further increased by a reasonable combination of X, Y, and R in parent structure II. It could be found that the title compounds IIa 2-[(2,4-dichlorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-1,3, 2-dioxaphosphinan-2-one and IIr 2-[(4-chloro-2-methyl-phenoxy)acetoxy](methyl) methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one possess high activity and a broad spectrum against all of the test broadleaf weeds with 70-100% inhibition effect at a dosage of 75 g ai/ha, and the title compounds IIa and IIr are safe for corn and wheat at a dosage of 150 g ai/ha. Furthermore, the title compound IIa possesses low rat toxicity. These results suggest that the title compounds IIa and IIr could be potential and selective postemergence herbicides for further development.

Full text of DOI:10.1021/jf301829m

Article
pubs.acs.org/JAFC
Synthesis and Herbicidal Activity of 2‑(Substituted
phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one
Wei Wang, Hong-Wu He,* Na Zuo, Hai-Feng He, Hao Peng,* and Xiao-Song Tan
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, Institute of Pesticide Chemistry, College of Chemistry,
Central China Normal University, Wuhan 430079, People’s Republic of China
ABSTRACT: A series of 2-(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-ones IIa−s were designed
and synthesized on the basis of the previous work for the modification of alkylphosphonates I, and their structures were
confirmed by 1H NMR, 31P NMR, 13C NMR, IR, MS, and elemental analysis. Their herbicidal activities against seven species of
weeds were evaluated in a greenhouse. A part of the title compounds such as IIa−g, IIk, IIo, and IIr exhibited significant
postemergence herbicidal activity against Abutilon theophrasti, Brassica juncea, Amaranthus retroflexus, and Eclipta prostrate at a
dosage of 150 g ai/ha. Structure−activity relationship analyses indicated that the introduction of a phosphorus-containing
heterocyclic ring had a favorable effect on herbicidal activity, and their herbicidal activity could be further increased by a
reasonable combination of X, Y, and R in parent structure II. It could be found that the title compounds IIa 2-[(2,4-
dichlorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one and IIr 2-[(4-chloro-2-methyl-phenoxy)-
acetoxy](methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one possess high activity and a broad spectrum against all of the
test broadleaf weeds with 70−100% inhibition effect at a dosage of 75 g ai/ha, and the title compounds IIa and IIr are safe for
corn and wheat at a dosage of 150 g ai/ha. Furthermore, the title compound IIa possesses low rat toxicity. These results suggest
that the title compounds IIa and IIr could be potential and selective postemergence herbicides for further development.
KEYWORDS: synthesis, herbicidal activity, cyclophosphonate, phosphonate
herbicide was further developed and has got temporary
registration from ICAMA in China.18,19
INTRODUCTION
■
Reduced crop yield can be a major consequence of weeds in
agriculture due mainly to the strong competition they pose for
crops in obtaining light, water, nutrients, and physical space.1−3
As the main weed control tool, herbicides play a very important
role in modern agriculture. Unfortunately, an inevitable
problem associated with the use of herbicides is the occurrence
of herbicide-resistant weeds. Therefore, it is necessary to
develop efficient herbicides with novel structures and modes of
action to overcome the resistance of weeds.
As an important class of pesticides, organic phosphorus
compounds display a wide range of biological activities and
have attracted considerable attention as the main source of lead
compounds in agrochemicals.4−7 A detailed study of
acylphosphinates and acylphosphonates revealed that these
analogues of pyruvate could be designed as mechanism-based
inhibitors of pyruvate dehydrogenase complex (PDHc).8
However, they are not active enough for full development as
herbicides.8−10 These findings prompted us to perform our
own study for novel PDHc inhibitors as potential herbicides.
In our previous work,11−17 a series of alkylphosphonate
derivatives with general structure I (Scheme 1) were designed
and synthesized, and the ensuing bioassay results exhibited
higher herbicidal activities in some cases. SAR analyses
indicated that chlorine or fluorine atoms as X and Y at the 2-
and 4-positions on a phenoxy ring and a smaller group (MeO)
attached to the phosphorus as R1 and R2 in general structure I
were beneficial to herbicidal activity. Among these alkylphosph-
onates I, the compound I-1 (HW02) as a competitive inhibitor
of PDHc was found to be the most effective compound against
broadleaf weeds. The compound I-1 as a novel postemergence
On the other hand, a variety of the reports regarding
synthetic studies of cyclophosphonate analogues have been
presented because phosphorus-containing heterocyclic moiety
can increase bioactivity20 and stability21 through replacement of
simple phosphonate. This encouraged us to design a series of
cyclophosphonates (Scheme 1) on the basis of the
alkylphosphonates I and further study the relationship of
structure−herbicidal activity. It is very interesting to examine
the effect on herbicidal activity by introduction of a
phosphorus-containing heterocyclic ring. Here, we report the
synthesis of a series of 2-(substituted phenoxyacetoxy)alkyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-ones IIa−s and evaluation
for their herbicidal activity.
MATERIALS AND METHODS
■
Synthesis Procedures. Chemicals and reagents were obtained
from commercial sources, and all of the solvents were dried and
purified by standard tecniques prior to use. Column chromatography
was carried out with Merck silica gel (200−300 mesh). Melting points
(mp) were measured on a Buchi B-545 melting point apparatus and
were uncorrected. IR spectra were recorded as KBr pellets on a Perkin-
1
Elmer Fourier transform infrared spectrophotometer. H NMR were
recorded on Varian XL-400 spectrometer at 400 MHz or Varian XL-
600 spectrometer at 600 MHz using tetramethylsilane as internal
standard (solvent CDCl3). 13C and 31P NMR were recorded on a
Received: April 27, 2012
Revised: July 10, 2012
Accepted: July 20, 2012
Published: July 20, 2012
© 2012 American Chemical Society
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Scheme 1. Chemical Modification of Lead Structure I
Varian XL-400 spectrometer at 400 MHz (solvent CDCl3). 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 Finnigen
TRACE spectrometer and API2000LC/MS. Elemental analyses were
performed by a Vario EL III elemental analyzer.
2-[(2,4-Dichlorophenoxy)acetoxy](furan-2-yl)methyl-5,5-dimeth-
yl-1,3,2-dioxaphosphinan-2-one (IIb). White solid; yield 72%; mp,
110−113 °C. IR (KBr, cm−1): ν 3114, 2966, 1769, 1483, 1282, 1194,
1072, 1009, 857, 805. 1H NMR (400 MHz, CDCl3): δ 7.47 (s, 1H, 5-
furanyl-H), 7.37 (d, J = 2.4 Hz, 1H, 3-phenyl-H), 7.13−6.43 (m, 4H),
6.42 (d, J = 12.8 Hz, 1H, PCHO), 4.79 (s, 2H, OCH2CO), 4.14−4.05
(m, 4H, 2 × (OCH2)), 1.23 (s, 3H), 0.94 (s, 3H). 13C NMR (100
MHz, CDCl3): 167.01, 156.11, 145.34, 145.01, 129.75, 127.61, 125.83,
Phosphorus trichloride, triethyl amine, and thionyl chloride were
distilled before the reaction.
1
123.79, 113.70, 113.10, 111.36, 65.29, 63.27 (d, JC−P = 168.99 Hz),
General Procedure for the Synthesis of Compounds 2a−g.
Compounds 2a−g could be prepared by the reaction of the
intermediate 1 (10 mmol) and several kinds of aldehydes (10
mmol) in chloroform (10 mL) using triethylamine (5 mmol) as a
catalyst in yield of 60−90%. Also, the intermediate 1 was synthesized
from neopentyl glycol, which was used directly as obtained
commercially.
32.43, 21.55, 20.60. 31P NMR (160 MHz, CDCl3): δ 6.16. EI-MS m/z
(%): 449 (M+, 1), 245 (25), 229 (40), 175 (29), 147 (21), 133 (70),
111 (22), 95 (34), 81 (41), 69 (100). Anal. Calcd for C18H19Cl2O7P:
C, 48.13; H, 4.26. Found: C, 48.67; H, 3.87.
2-[(2,4-Dichlorophenoxy)acetoxy](phenyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIc). White solid; yield 67%; mp,
150−151 °C. IR (KBr, cm−1): ν 3092, 2963, 1770, 1485, 1274, 1193,
1072, 1070, 864, 800. 1H NMR (400 MHz, CDCl3): δ 7.44−6.73 (m,
8H, −C6H5, −C6H3), 6.36 (d, J = 12.4 Hz, 1H, PCHO), 4.82 (s, 2H,
OCH2CO), 4.07−4.04 (m, 4H, 2 × (OCH2)), 1.16 (s, 3H), 0.90 (s,
3H). 13C NMR (100 MHz, CDCl3): 167.21, 152.09, 132.96, 130.35,
129.31, 128.73, 127.95, 127.67, 127.29, 123.86, 114.53, 71.12 (d, 1JC−P
= 165.40 Hz), 66.17, 32.43, 21.60, 20.78. 31P NMR (160 MHz,
CDCl3): δ 8.38. EI-MS m/z (%): 458 (M+ + 1, 13), 311 (9), 245 (11),
229 (28), 177 (43), 175 (77), 162 (11), 147 (16), 137 (15), 136 (26),
135 (90), 121 (100), 90 (90). Anal. Calcd for C20H21Cl2O6P: C,
52.30; H, 4.61. Found: C, 52.79; H, 4.47.
All of the intermediates 2a−g were synthesized according to the
methods described in the literature,22−24 in which the compounds
2b,23,24 2c,22 2d,22 2e,22 and 2g22 have been reported.
1
Data for 2a (R = Me). Yield, 65%; mp, 94−96 °C. H NMR (400
MHz, CDCl3): δ 1.00 (s, 3H), 1.16 (s, 3H), 1.59−1.61 (m, 3H), 3.92−
4.15 (m, 4H), 5.50−5.52 (m, 1H). 31P NMR (160 MHz, CDCl3): δ
19.39. Anal. Calcd for C7H15O4P: C, 43.30; H, 7.79. Found: C, 43.41;
H, 7.99.
1
Data for 2f (R = n-Bu). Yield, 68%; mp, 120−121 °C. H NMR
(400 MHz, CDCl3): δ 0.91−0.86 (m, 3H), 1.02 (s, 3H), 1.15 (s, 3H),
1.35−1.31 (m, 4H), 1.94−1.93 (m, 2H), 4.16−3.91 (m, 4H), 5.58−
5.59 (m, 1H). 31P NMR (160 MHz, CDCl3) δ 21.09. Anal. Calcd for
C10H21O4P: C, 50.84; H, 8.96. Found: C, 51.20; H, 9.23.
2-[(2,4-Dichlorophenoxy)acetoxy](2,4-dichlorophenyl)methyl-
5,5-dimethyl-1,3,2-dioxaphosphinan-2-one (IId). White solid; yield
65%; mp, 169−170 °C. IR (KBr, cm−1): ν 3102, 2974, 1772, 1480,
General Procedure for the Synthesis of Compounds 3 and 4.
Compound 3 could be prepared from substituted phenol and
chloroacetic acid according to the methods given in ref 25. A mixture
containing substituted phenoxyacetyl acid 3 (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 4 was obtained with a yield of 85−90%.
General Procedure for the Synthesis of the Title Compounds IIa−
s. A solution of substituted phenoxyacetyl chlorides 4 (3.3 mmol) in
trichloromethane (15 mL) was added to a stirred mixture of α-
hydroxyalkylphosphonates 2 (3 mmol) and triethylamine (3.3 mmol)
in chloroform (20 mL) at 0−5 °C. The resultant mixture was stirred
for 3−5 h at room temperature and then for 1−2 h at 40 °C. 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 (2:1, v/v) to
give the corresponding pure title compounds IIa−s. Their structures
were confirmed by 1H NMR, 13C NMR, 31P NMR, IR, MS, and
elemental analysis. The physicochemical properties and spectroscopic
data for all of the title compounds IIa−s are as follows.
1
1288, 1179, 1057, 1006, 840, 813. H NMR (400 MHz, CDCl3): δ
7.63−6.82 (m, 6H, −C6H3, −C6H3), 6.73 (d, J = 8.8 Hz, 1H, PCHO),
4.81 (d, J = 4.0 Hz, 2H, OCH2CO), 4.17−4.01 (m, 4H), 1.21 (s, 3H),
0.95 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.31, 152.01, 138.62,
133.53, 132.89, 132.41, 131.64, 130.73, 130.29, 127.81, 126.64, 123.65,
1
114.38, 71.36 (d, JC−P = 165.90 Hz), 65.59, 32.24, 21.60, 20.78. 31P
NMR (160 MHz, CDCl3): δ 5.84. EI-MS m/z (%): 528 (M+, 5), 491
(5), 308 (28), 175 (57), 145 (23), 133 (100), 69 (71). Anal. Calcd for
C20H19Cl4O6P: C, 45.48; H, 3.63. Found: C, 45.94; H, 3.44.
2-[(2,4-Dichlorophenoxy)acetoxy](4-chlorophenyl)methyl-5,5-di-
methyl-1,3,2-dioxaphosphinan-2-one (IIe). White solid; yield, 70%;
mp, 120−121 °C. IR (KBr, cm−1): ν 3090, 2978, 1768, 1484, 1273,
1
1189, 1073, 1020, 830, 815. H NMR (400 MHz, CDCl3): δ 7.41−
6.72 (m, 7H, −C6H4, −C6H3), 6.30 (d, J = 12.4 Hz, 1H, PCHO), 4.80
(s, 2H, OCH2CO), 4.10−3.91 (m, 4H, 2 × (OCH2)), 1.16 (s, 3H),
0.92 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.28, 152.55, 141.90,
133.66, 131.82, 130.99, 128.07, 127.63, 127.15, 113.99, 69.98 (d, 1JC−P
= 165.80 Hz), 66.01, 32.09, 21.56, 20.33. 31P NMR (160 MHz,
CDCl3): δ 7.48. EI-MS m/z (%): 494 (M+ + 1, 5), 274 (24), 175 (29),
133 (100), 69 (63). Anal. Calcd for C20H20Cl3O6P: C, 48.66; H, 4.08.
Found: C, 48.89; H, 3.83.
2-[(2,4-Dichlorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIa). White solid; yield, 64%; mp, 62−
64 °C. IR (KBr, cm−1): ν 3091, 2967, 1764, 1483, 1237, 1197, 1053,
2-[(2,4-Dichlorophenoxy)acetoxy](i-propyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIf). White solid; yield, 86%; mp,
120−121 °C. IR (KBr, cm−1): ν 3076, 2971, 1759, 1480, 1282, 1205,
1057, 1012, 834, 808. 1H NMR (400 MHz, CDCl3): δ 7.42 (d, 1H, J =
2.4 Hz, 3-phenyl-H), 7.19−7.16 (dd, 1H, J = 2.4 Hz, J = 2.4 Hz, 5-
phenyl-H), 6.78 (d, 1H, J = 8.8 Hz, 6-phenyl-H), 5.31−5.27 (t, 1H, J =
7.2 Hz, PCHO), 4.80 (d, J = 4.8 Hz, 2H, OCH2CO), 4.15−3.92 (m,
4H, 2 × (OCH2)), 2.37−2.33 (m, 1H), 1.15 (s, 3H), 1.13−1.01 (m,
6H), 0.99 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.65, 152.01,
1
1000, 844, 805. H NMR (400 MHz, CDCl3): δ 7.41−6.78 (m, 3H,
−C6H3), 5.50 (m, 1H, PCHO), 4.76 (d, J = 4.0 Hz, 2H,
−OCH2CO−), 4.15−3.92 (m, 4H, 2 × (OCH2)), 1.61−1.59 (m,
3H), 1.16 (s, 3H), 1.00 (s, 3H). 13C NMR (100 MHz, CDCl3):
167.07, 153.97, 129.95, 127.82, 126.03, 123.75, 114.03, 65.50, 65.35
1
(d, JC−P = 165.30 Hz), 32.09, 21.07, 20.18, 14.37. 31P NMR (160
MHz, CDCl3): δ 12.35. EI-MS m/z (%): 397 (M+, 6), 178 (30), 133
(32), 111 (39), 95 (14), 69 (100). Anal. Calcd for C15H19Cl2O6P: C,
45.36; H, 4.82. Found: C, 45.11; H, 4.89.
1
133.73, 130.34, 127.51, 123.99, 114.38, 72.70 (d, JC−P = 159.60 Hz),
65.87, 32.36, 28.95, 21.51, 20.95, 18.13. 31P NMR (160 MHz, CDCl3):
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δ 20.13. EI-MS m/z (%): 426 (M+ + 1, 4), 263 (14), 206 (36), 191
(100), 175 (34), 133 (71), 69 (72). Anal. Calcd for C17H23Cl2O6P: C,
48.02; H, 5.45. Found: C, 48.26; H, 5.04.
(79). Anal. Calcd for C19H22ClO7P: C, 53.22; H, 5.17. Found: C,
53.32; H, 5.34.
2-[(2-Chlorophenoxy)acetoxy](phenyl)methyl-5,5-dimethyl-1,3,2-
dioxaphosphinan-2-one (IIl). Yellow solid; yield, 82%; mp, 87−88
°C. IR (KBr, cm−1): ν 3014, 2968, 1752, 1590, 1493, 1293, 1190,
1056, 837. 1H NMR (400 MHz, CDCl3): δ 7.43−6.79 (m, 9H,
−C6H5, −C6H4), 6.37 (d, 1H, J = 12.4 Hz, PCHO), 4.84 (s, 2H,
OCH2CO), 4.16−3.96 (m, 4H, 2 × (OCH2)), 1.17 (s, 3H), 0.90 (s,
3H). 13C NMR (100 MHz, CDCl3): 166.96, 156.02, 132.05, 129.15,
128.88, 128.73, 128.67, 127.90, 127.83, 122.87, 113.68, 71.45 (d, 1JC−P
= 164.60 Hz), 66.06, 32.30, 21.67, 20.71. 31P NMR (160 MHz,
CDCl3): δ 8.24. EI-MS m/z (%): 424 (M+, 3), 240 (22), 141 (34), 133
(86), 105 (45), 91 (14), 77 (51), 69 (100). Anal. Calcd for
C20H22ClO6P: C, 56.55; H, 5.22. Found: C, 56.74; H, 5.46.
2-[(4-Chlorophenoxy)acetoxy](phenyl)methyl-5,5-dimethyl-1,3,2-
dioxaphosphinan-2-one (IIm). White solid; yield, 78%; mp, 59−60
°C. IR (KBr, cm−1): ν 3064, 2967, 1755, 1594, 1492, 1291, 1190,
2-[(2,4-Dichlorophenoxy)acetoxy](n-butyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIg). White solid; yield, 72%; mp, 75−
76 °C. IR (KBr, cm−1): ν 3070, 2953, 1755, 1478, 1281, 1198, 1068,
1
1009, 838, 799. H NMR (400 MHz, CDCl3): δ 7.41 (d, 1H, J = 2.4
Hz, 3-phenyl-H), 7.19−7.16 (dd, 1H, J = 2.4 Hz, J = 2.4 Hz, 5-phenyl-
H), 6.78 (d, 1H, J = 8.8 Hz, 6-phenyl-H), 5.50−5.47 (m, 1H, PCHO),
4.78−4.69 (s, 2H, OCH2CO), 4.16−3.91 (m, 4H, 2 × (OCH2)),
1.94−1.93 (m, 2H), 1.35−1.31 (m, 4H), 1.15 (s, 3H), 1.02 (s, 3H),
0.91−0.86 (m, 3H). 13C NMR (100 MHz, CDCl3): 167.81, 152.26,
1
132.99, 130.47, 127.29, 124.13, 113.75, 71.65 (d, JC−P = 162.40 Hz),
66.11, 32.39, 24.31, 21.70, 21.31, 20.95, 18.76, 15.11. 31P NMR (160
MHz, CDCl3): δ 14.55. Anal. Calcd for C18H25Cl2O6P: C, 49.22; H,
5.74. Found: C, 49.55; H, 5.39.
2-[(2-Chlorophenoxy)acetoxy](furan-2-yl)methyl-5,5-dimethyl-
1
1,3,2-dioxaphosphinan-2-one (IIh). Yellow oil; yield, 82%; n20
1057, 1008, 835. H NMR (400 MHz, CDCl3): δ 7.44−6.80 (m, 9H,
D
1.5211. IR (KBr, cm−1): ν 3124, 2971, 1765, 1596, 1492, 1291,
1170, 1061, 1011, 826. 1H NMR (400 MHz, CDCl3): δ 7.48−6.53 (m,
6H, C6H4, 5 and 4-furanyl-H), 6.49 (d, 1H, J = 14.4 Hz, PCHO), 6.42
(s, 1H, 3-furanyl-H), 4.71 (s, 2H, OCH2CO), 4.12−4.05 (m, 4H, 2 ×
(OCH2)), 1.23 (s, 3H), 0.94 (s, 3H). 13C NMR (100 MHz, CDCl3):
167.19, 155.08, 144.89, 143.91, 129.17, 128.82, 126.34, 115.72, 115.47,
−C6H5, −C6H4), 6.36 (d, 1H, J = 12.0 Hz, PCHO), 4.80−4.69 (m,
2H, OCH2CO), 4.11−3.92 (m, 4H, 2 × (OCH2)), 1.16 (s, 3H), 0.91
(s, 3H). 13C NMR (100 MHz, CDCl3): 167.30, 156.02, 129.73,
1
129.28, 128.85, 127.99, 127.93, 125.51, 115.85, 70.86 (d, JC−P
=
165.30 Hz), 65.40, 32.13, 21.59, 20.80. 31P NMR (160 MHz, CDCl3):
δ 8.72. EI-MS m/z (%): 424 (M+, 1), 240 (43), 172 (4), 141 (30), 133
(85), 105 (39), 91 (7), 77 (50), 69 (100). Anal. Calcd for
C20H22ClO6P: C, 56.55; H, 5.22. Found: C, 56.93; H, 5.51.
1
113.11, 111.33, 65.32, 63.41 (d, JC−P = 170.80 Hz), 32.37, 21.59,
20.21. 31P NMR (160 MHz, CDCl3): δ 6.08. EI-MS m/z (%): 414
(M+, 3), 245 (30), 229 (17), 141 (37), 133 (75), 113 (35), 95 (32), 81
(45), 69 (100). Anal. Calcd for C18H20ClO7P: C, 52.12; H, 4.86.
Found: C, 52.33; H, 4.52.
2-[(4-Chloro-3-methylphenoxy)acetoxy](phenyl)methyl-5,5-di-
methyl-1,3,2-dioxaphosphinan-2-one (IIn). Yellow solid; yield, 80%;
mp, 70−71 °C. IR (KBr, cm−1): ν 3065, 2966, 1766, 1607, 1479, 1277,
1165, 1059, 1008, 837. 1H NMR (400 MHz, CDCl3): δ 7.43−6.64 (m,
8H), 6.35 (d, 1H, J = 16.0 Hz, PCHO), 4.73 (d, 2H, J = 2.4 Hz,
OCH2CO), 4.08−3.97 (m, 4H, 2 × (OCH2)), 2.31 (s, 3H, PhCH3),
1.16 (s, 3H), 0.91 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.31,
155.63, 137.55, 132.33, 129.67, 128.83, 128.51, 127.39, 126.77, 117.03,
113.44, 71.71 (d, 1JC−P = 165.90 Hz), 65.29, 32.11, 21.49, 20.61, 20.38.
31P NMR (160 MHz, CDCl3): δ 8.89. EI-MS m/z (%): 438 (M+, 3),
2-[(4-Chlorophenoxy)acetoxy](furan-2-yl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIi). Yellow oil; yield, 80%; n20
D
1.5213. IR (KBr, cm−1): ν 3125, 2970, 1766, 1595, 1492, 1291,
1170, 1062, 1011, 826. 1H NMR (400 MHz, CDCl3): δ 7.47 (s, 1H, 5-
furanyl-H), 7.23 (d, 2H, J = 8.4 Hz, 3 and 5-phenyl-H), 6.81 (d, 2H, J
= 8.4 Hz, 2 and 6-phenyl-H), 6.72 (s, 1H, 4-furanyl-H), 6.50 (d, 1H, J
= 13.2 Hz, PCHO), 6.42 (s, 1H, 3-furanyl-H), 4.76 (s, 2H, OCH2CO),
4.14−4.02 (m, 4H, 2 × (OCH2)), 1.22 (s, 3H), 0.94 (s, 3H). 13C
NMR (100 MHz, CDCl3): 167.27, 155.90, 145.01, 144.11, 129.40,
295 (6), 241 (2), 240 (12), 175 (39), 145 (46), 133 (91), 105 (38), 91
(13), 77 (26), 69 (100). Anal. Calcd for C21H24ClO6P: C, 57.48; H,
5.51. Found: C, 57.39; H, 5.73.
1
115.79, 113.10, 113.05, 111.05, 65.20, 63.35 (d, JC−P = 170.80 Hz),
2-[(4-Chloro-2-methylphenoxy)acetoxy](phenyl)methyl-5,5-di-
methyl-1,3,2-dioxaphosphinan-2-one (IIo). Yellow solid; yield, 80%;
mp, 98−100 °C. IR (KBr, cm−1): ν 3124, 2975, 1770, 1601, 1494,
32.41, 21.57, 20.58. 31P NMR (160 MHz, CDCl3): δ 6.02. EI-MS m/z
(%): 414 (M+, 2), 245 (12), 229 (39), 175 (5), 141 (21), 133 (63),
111 (14), 95 (35), 81 (50), 69 (100). Anal. Calcd for C18H20ClO7P: C,
52.12; H, 4.86. Found: C, 52.46; H, 5.38.
1
1276, 1177, 1071, 1012, 952, 837. H NMR (400 MHz, CDCl3): δ
7.45−6.56 (m, 8H, −C6H5, −C6H3), 6.36 (d, 1H, J = 12.0 Hz,
PCHO), 4.76 (s, 2H, OCH2CO), 4.11−3.86 (m, 4H, 2 × (OCH2)),
2.26 (s, 3H, PhCH3), 1.13 (s, 3H), 0.89 (s, 3H). 13C NMR (100 MHz,
CDCl3): 167.36, 154.27, 132.16, 130.71, 129.17, 128.94, 128.66,
2-[(4-Chloro-3-methylphenoxy)acetoxy](furan-2-yl)methyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one (IIj). Yellow oil; yield, 82%;
n20 1.5230. IR (KBr, cm−1): ν 3124, 2968, 1770, 1600, 1482, 1291,
D
1166, 1062, 1012, 828. 1H NMR (400 MHz, CDCl3): δ 7.47 (s, 1H, 5-
furanyl-H), 7.24−6.69 (m, 4H, 2, 5, and 6-phenyl-H, 4-furanyl-H),
6.50 (d, H, J = 14.4 Hz, PCHO), 6.42 (s, 1H, 3-furanyl-H), 4.70 (s,
2H), 4.16−4.03 (m, 4H), 2.32 (s, 3H), 1.23 (s, 3H), 0.96 (s, 3H). 13C
NMR (100 MHz, CDCl3): 167.31, 156.11, 145.30, 143.87, 137.23,
1
127.89, 126.31, 126.17, 117.16, 70.53 (d, JC−P = 164.60 Hz), 65.47,
32.33, 21.46, 20.61, 16.07. 31P NMR (160 MHz, CDCl3): δ 8.55. EI-
MS m/z (%): 438 (M+, 10), 288 (16), 244 (51), 241 (13), 240 (100),
173 (21), 155 (36), 133 (59), 125 (46), 105 (33), 91 (26), 77 (39), 69
(72). Anal. Calcd for C21H24ClO6P: C, 57.48; H, 5.51. Found: C,
57.59; H, 5.63.
129.80, 127.03, 117.01, 112.92, 112.74, 111.03, 65.07, 63.78 (d, 1JC−P
=
170.10 Hz), 32.19, 21.47, 20.61, 20.25. 31P NMR (160 MHz, CDCl3):
δ 6.11. EI-MS m/z (%): 428 (M+, 8), 278 (20), 234 (37), 230 (10),
155 (57), 125 (55), 81 (58), 69 (100). Anal. Calcd for C19H22ClO7P:
C, 53.22; H, 5.17. Found: C, 53.95; H, 6.15.
2-[(4-Chloro-3-methylphenoxy)acetoxy](methyl)methyl-5,5-di-
methyl-1,3,2-dioxaphosphinan-2-one (IIp). White solid; yield, 64%;
mp, 104−106 °C. IR (KBr, cm−1): ν 3077, 2970, 1764, 1485, 1285,
1206, 1060, 1009, 953, 839, 801. 1H NMR (600 MHz, CDCl3): δ 7.24
(d, 1H, J = 9.0 Hz, 5-phenyl-H), 6.78−6.64 (m, 2H, 2 and 6-phenyl-
H), 5.52−5.47 (m, 1H, PCHO), 4.67 (s, 2H, OCH2CO), 4.13−3.98
(m, 4H, 2 × (OCH2)), 2.33 (s, 3H, PhCH3), 1.60−1.56 (dd, 3H, J =
7.2 Hz, J = 7.2 Hz, PCH(CH3)O), 1.17 (s, 3H), 0.99 (s, 3H). 13C
NMR (100 MHz, CDCl3): 167.54, 155.83, 137.21, 129.62, 126.91,
2-[(4-Chloro-2-methylphenoxy)acetoxy](furan-2-yl)methyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one (IIk). White solid; yield,
80%; mp, 63−65 °C. IR (KBr, cm−1): ν 3122, 2971, 1771, 1492,
1291, 1171, 1063, 1012, 947, 918, 808. 1H NMR (400 MHz, CDCl3):
δ 7.47 (s, 1H, 5-furanyl-H), 7.13−7.03 (m, 2H, 3 and 5-phenyl-H),
6.72 (s, 1H, 6-phenyl-H), 6.57 (d, 1H, J = 8.4 Hz, 4-furanyl-H), 6.50
(d, 1H, J = 14.4 Hz, PCHO), 6.42 (s, 1H, 3-furanyl-H), 4.72 (s, 1H,
OCH2CO), 4.11−3.98 (m, 4H, 2 × (OCH2)), 2.25 (s, 3H, PhCH3),
1.21 (s, 3H), 0.93 (s, 3H). 13C NMR (100 MHz, CDCl3): 167.37,
156.99, 145.01, 143.73, 130.89, 129.24, 127.93, 126.55, 126.07, 113.11,
110.97, 65.13, 63.87 (d, 1JC−P = 170.60 Hz), 32.57, 21.39, 20.78, 16.09.
31P NMR (160 MHz, CDCl3): δ 6.23. EI-MS m/z (%): 428 (M+, 6),
1
117.02, 112.92, 65.23, 65.06 (d, JC−P = 165.30 Hz), 32.38, 21.44,
20.67, 20.21, 14.69. 31P NMR (160 MHz, CDCl3): δ 12.65. EI-MS m/
z (%): 376 (M+, 3), 178 (54), 158 (17), 155 (16), 150 (19), 133 (26),
124 (33), 111 (92), 88 (23), 69 (100). Anal. Calcd for C16H22ClO6P:
C, 51.01; H, 5.89. Found: C, 51.28; H, 6.03.
2-[(2-Chlorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIq). White solid; yield, 68%; mp, 99−
101 °C. IR (KBr, cm−1): ν 3098, 2974, 1775, 1493, 1286, 1194, 1066,
384 (1), 278 (11), 234 (37), 230 (10), 155 (57), 125 (55), 81 (58), 69
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Journal of Agricultural and Food Chemistry
Article
1
1003, 953, 799. H NMR (600 MHz, CDCl3): δ 7.27−6.81 (m, 4H,
containing test soil and grown in a greenhouse at 20−25 °C. After the
plants had reached the four-leaf stage, the spraying treatment was
conducted at different dosages by diluting the formulation of the
selected compounds. The visual injury and growth state of the
individual plant were observed at regular intervals. The final evaluation
for crops safety of the selected compounds was conducted by visual
observation in 30 days after treatment on the 0−100 scale (0 = no
injury, 10 = chlorosis, 100 = death).
C6H4), 5.50−5.48 (m, 1H, PCHO), 4.68 (s, 2H, OCH2CO), 4.14−
3.97 (m, 4H, 2 × (OCH2)), 1.60−1.56 (q, 3H, J = 7.8 Hz,
PCH(CH3)O), 1.16 (s, 3H), 1.01 (s, 3H). 13C NMR (100 MHz,
CDCl3): 167.17, 155.71, 129.15, 128.92, 126.42, 115.60, 115.53, 65.04,
64.81 (d, JC−P = 165.30 Hz), 32.11, 21.13, 20.46, 14.41. 31P NMR
1
(160 MHz, CDCl3): δ 13.53. EI-MS m/z (%): 362 (M+, 3), 178 (33),
150 (11), 141 (17), 133 (23), 111 (100), 96 (9), 75 (24), 69 (80).
Anal. Calcd for C15H20ClO6P: C, 49.67; H, 5.56. Found: C, 50.03; H,
5.83.
Toxicity. Mammalian toxicity was performed according to the
Chinese standard procedure. The title compound IIa was selected for
mammalian toxicity testing.
2-[(4-Chloro-2-methylphenoxy)acetoxy](methyl)methyl-5,5-di-
methyl-1,3,2-dioxaphosphinan-2-one (IIr). White solid; yield, 68%;
mp, 82−84 °C. IR (KBr, cm−1): ν 3079, 2972, 1768, 1491, 1231, 1184,
RESULTS AND DISCUSSION
■
1
1056, 1010, 947, 877, 805. H NMR (600 MHz, CDCl3): δ 7.14 (s,
Synthesis of the Title Compounds IIa−s. The title
compounds IIa−s were prepared by condensation of
intermediates 2a−g with substituted phenoxyacetyl chlorides
4 in the presence of triethylamine or pyridine as a base and
chloroform as a solvent (Scheme 2). The intermediates 2a−g
1H, 3-phenyl-H), 7.10−7.07 (m, 1H, 5-phenyl-H), 6.61 (d, 1H, J = 8.4
Hz, 6-phenyl-H), 5.50−5.46 (m, 1H, PCHO), 4.69 (d, 2H, J = 4.2 Hz,
OCH2CO), 4.14−3.91 (m, 4H, 2 × (OCH2)), 2.25 (s, 3H, PhCH3),
1.60−1.55 (q, 3H, J = 8.4 Hz, PCH(CH3)O), 1.14 (s, 3H), 1.00 (s,
3H). 13C NMR (100 MHz, CDCl3): 167.44, 153.99, 136.56, 130.11,
1
127.05, 117.23, 113.04, 65.49, 65.30 (d, JC−P = 164.90 Hz), 32.31,
21.43, 20.66, 20.37, 14.88. 31P NMR (160 MHz, CDCl3): δ 12.33. EI-
MS m/z (%): 376 (M+, 5), 236 (4), 193 (16), 178 (38), 155 (28), 133
(49), 111 (43), 77 (37), 69 (100). Anal. Calcd for C16H22ClO6P: C,
51.01; H, 5.89. Found: C, 51.08; H, 6.23.
Scheme 2. Synthetic Route of 2-[(Substituted
phenoxyacetoxy)alkyl]-5,5-dimethyl-1,3,2-dioxaphosphinan-
2-one IIa−s
2-[(4-Chlorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (IIs). White solid; yield, 74%; mp, 62−
64 °C. IR (KBr, cm−1): ν 3093, 2976, 1776, 1495, 1286, 1191, 1070,
1004, 952, 838, 798. 1H NMR (600 MHz, CDCl3): δ 7.26 (d, 2H, J =
8.4 Hz, 3 and 5-phenyl-H), 6.83 (d, 2H, J = 8.4 Hz, 2 and 6-phenyl-H),
5.52−5.47 (m, 1H, PCHO), 4.68 (s, 2H, OCH2CO), 4.14−3.97 (m,
4H, 2 × (OCH2)), 1.60−1.56 (dd, 3H, J = 7.2 Hz, J = 7.2 Hz,
PCH(CH3)O), 1.16 (s, 3H), 1.01 (s, 3H). 13C NMR (100 MHz,
CDCl3): 167.19, 153.91, 129.55, 125.38, 114.01, 66.70, 65.55 (d, 1JC−P
= 165.60 Hz), 32.12, 21.18, 20.33, 14.75. 31P NMR (160 MHz,
CDCl3): δ 12.14. EI-MS m/z (%): 362 (M+, 5), 178 (40), 150 (11),
141 (25), 133 (33), 111 (91), 99 (6), 77 (13), 74 (18), 69 (100). Anal.
Calcd for C15H20ClO6P: C, 49.67; H, 5.56. Found: C, 49.81; H, 5.76.
Greenhouse Herbicidal Activity. The herbicidal activities of the
title compounds IIa−s against monocotyledonous weeds such as
Echinochloa crusgalli, Setaira viridis, and Digitaria sanguinalis and
dicotyledonous weeds such as Abutilon theophrasti, Brassica juncea,
Amaranthus retroflexus, and Eclipta prostrate were evaluated at 150 g ai/
ha using the compounds I-1 (HW02) and I-2 as references according
to a previous reported procedure.18,19 Some of the title compounds
IIa-g and IIr were then selected for further test at 75 and 37.5 g ai/ha
using the compound I-1 (HW02) as a positive control, and the weed
species were the same as the first test except for Abutilon theophrasti.
Finally, a broad spectrum test was made using more weed species such
as Amaranthus retroflexus, Brassica chinensis, Pharbitis nil, Raphanus
sativus, Ammannia baccifera, Monochoia vaginalis, Brassica oleracea,
Brassica campestris, Chenopodium album, and Brassica juncea for the
title compounds IIa and IIb at 150 and 75 g ai/ha. Glyphosate was
selected as a positive control.
Weed seeds were planted in 9 cm-diameter plastic boxes containing
artificial mixed soil. Before plant emergence, the boxes were covered
with plastic film to keep moist. Plants were grown in the greenhouse.
Fresh weight of the above ground tissues was measured 10 days after
treatment. The inhibition percent is used to describe the control
efficiency of compounds. All test compounds were dissolved in N,N-
dimethylformamide with the addition of a little Tween 20 and then
were sprayed using a laboratory belt sprayer delivering at 750 L/ha-
spray-volume. The mixture of the same amount of water, N,N-
dimethylformamide, and Tween 20 was sprayed as control. Activity
numbers represent percent displaying herbicidal damage as compared
to control. The diluted formulation solutions were applied for
postemergence treatment,; dicotyledon weeds were treated at the
two-leaf stage, and monocotyledon weeds were treated at the one-leaf
stage, respectively.
were prepared according to existing methods.22−24 The
substituted phenoxyacetic acids 3 were prepared by con-
densation of corresponding substituted phenols with chloro-
acetic acid in the presence of alkali such as sodium hydroxide.
The structures of the title compounds IIa−s were characterized
1
by H NMR, 13C NMR, 31P NMR, IR, MS, and elemental
analysis. The title compounds IIa−s exhibit some characteristic
peakes at δ = 0.89−1.23 (2s, 6H, 2CH3) and δ = 5.45−6.74 (d
1
or t or m, 1H, PCHO), respectively, in the H NMR. The
typical carbon resonance at δC 166−168 in the 13C NMR
spectra of IIa−s also confirms the presence of a carbon−oxygen
double bond. The typical phosphorus resonance at δP 5.85−
13.09 in the 31P NMR spectra of IIa−s reveals the presence of a
phosphorus center coupled to an adjacent CH.
Greenhouse Herbicidal Activity and Crop Selectivity.
The herbicidal activities of title compounds IIa−s were
evaluated at different doses in a set of experiments in a
greenhouse. As an initial evaluation, all of the title compounds
were tested at a dosage of 150 g ai/ha for postemergence
herbicidal activity on E. crusgalli, S. viridis, D. sanguinalis, A.
theophrasti, B. juncea, A. retroflexus, and E. prostrate.
Compounds I-1 (HW02) and I-2 (R1 and R2 = MeO, R =
Me, R3 = H in structure I) were selected as control. The results
Crop Selectivity. Conventional rice, corn, cotton, soybean, rape,
and wheat were respectively planted in plots (diameter = 12 cm)
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Journal of Agricultural and Food Chemistry
Article
Table 1. Structures and Herbicidal Activity of the Title Compounds IIa−s (Percent Inhibition)
post-emergence, 150 g ai/ha
a
a
a
a
a
a
a
compound
R
X
Y
EC
30 3.5
SV
DS
AT
BJ
AR
EP
IIa
IIb
IIc
IId
IIe
IIf
CH3
2-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
H
30
0
30 1.0
95 2.0
90 3.0
95 5.0
95 5.0
95 1.0
80 1.0
90 2.5
85 2.0
80 3.5
80 2.0
70 1.0
2-furyl
Ph
2-Cl
30
0
0
30 2.5
40 1.5
2-Cl
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
98
0
100
2,4-Cl2−Ph
4-Cl−Ph
i-Pr
2-Cl
0
95 1.0
90 1.0
95 1.0
100
98
80
0
2-Cl
0
0
80 1.5
85 2.5
85 1.0
70
0
2-Cl
0
100
100
75 2.0
75 1.5
70 3.5
50 1.0
55 2.0
70 3.0
65 3.0
50 2.0
60 3.5
75 2.5
IIg
IIh
IIi
n-Bu
2-furyl
2-furyl
2-furyl
2-furyl
Ph
2-Cl
0
90
70 2.0
70
70 4.0
100
0
2-Cl
0
90 1.5
70 2.5
85
0
4-Cl
H
0
0
55 5.0
60 1.0
IIj
3-CH3
2-CH3
2-Cl
4-Cl
4-Cl
H
0
65
90 1.0
75
0
IIk
IIl
60 4.0
100
75 1.0
60
65 1.5
100
0
0
0
70 1.5
65 1.0
0
IIm
IIn
IIo
IIp
IIq
IIr
IIs
I-1
I-2
Ph
4-Cl
H
70 2.5
65 1.0
90 1.0
70 1.0
0
Ph
3-CH3
2-CH3
4-Cl
4-Cl
4-Cl
3-CH3
H
65
0
Ph
40
0
0
100
CH3
70 2.5
70 3.0
60 2.0
90 1.5
60
75
0
0
CH3
2-Cl
20 5.0
30 1.5
10 2.5
0
90
0
CH3
2-CH3
4-Cl
4-Cl
H
100
70
100
82 2.0
100
100
90 2.5
60 2.0
90 2.0
30 5.0
CH3
0
75 1.5
85 2.0
20 5.0
70 1.0
96 2.0
10 2.0
CH3
2-Cl
4-Cl
4-Cl
CH3
2-CH3
0
a
EC for Echinochloa crusgalli; SV for Setaira viridis; DS for Digitaria sanguinalis; AT for Abutilon theophrasti; BJ for Brassica juncea; AR for
Amaranthus retroflexus; EP for Eclipta prostrate.
Table 2. Further Herbicidal Testing of the Title Compounds IIa−g and IIr (Percent Inhibition)
a
a
a
a
a
a
compound
dosage (g ai/ha)
EC
SV
DS
BJ
AR
EP
50 1.5
70
IIa
37.5
75
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
90 2.0
95 5.0
85 5.0
90 3.0
90 2.0
70 1.5
75 3.0
50 2.5
70 2.0
0
IIb
37.5
75
60 2.0
62 3.0
50 1.0
55 2.0
30 1.0
34 2.0
0
IIc
37.5
75
50
0
95
0
80 2.0
IId
37.5
75
50 2.5
55 2.0
80 2.0
20
20
0
0
IIe
37.5
75
30 1.5
50 2.0
30 5.0
80 1.0
50 3.5
70 1.5
90
90 1.0
100
90
100
80 2.0
100
90 2.0
95
0
0
IIf
37.5
75
30
0
35 2.0
30 2.0
40 2.5
80 1.5
85 1.0
60 1.0
80 2.0
IIg
37.5
75
0
IIr
37.5
75
80
0
100
I-1 HW02
37.5
75
70 1.5
95 1.0
0
a
EC for Echinochloa crusgalli; SV for Setaira viridis; DS for Digitaria sanguinalis; BJ for Brassica juncea; AR for Amaranthus retroflexus; EP for Eclipta
prostrate.
are listed in Table 1. All of the title compounds displayed much
higher herbicidal activity against dicotyledonous plants than
against monocotyledons plants. A part of the title compounds
such as IIa−g, IIk, IIo, and IIr exhibited significant herbicidal
activity against A. theophrasti, B. juncea, A. retroflexus, and E.
prostrate. Especially, the title compounds IIa and IIr displayed
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Journal of Agricultural and Food Chemistry
Article
Table 3. Broad Spectrum Testing of the Title Compounds IIa,b and IIr
postemergence
a
a
a
a
a
a
a
a
a
a
compound
dosage (g ai/ha)
AR
BR
PN
100
RS
AB
MV
BO
BC
90 1.0
100
CA
BJ
IIa
75
150
75
75 3.0
95 1.0
70 2.0
80 1.0
80 1.0
85 2.0
70 2.0
80 3.0
70 1.0
80 1.0
70 2.0
80 1.0
90 2.0
95 1.0
80 1.0
85 3.0
80 1.0
80 1.0
60 2.0
65 3.0
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80 2.0
90 1.0
80 1.0
85 1.5
/
80 1.0
85 1.0
70 3.0
80 2.0
70 1.5
75 1.0
70 2.0
90 1.0
95 2.0
95 2.0
90 3.0
95 5.0
100
100
100
100
100
60
IIb
80 2.5
150
75
95 1.0
IIr
100
100
90 3.0
90 2.0
/
/
100
100
30 1.0
80 2.0
150
75
/
glyphosate
0
0
70 2.0
80 2.5
100
100
150
60
a
AR for Amaranthus retroflexus; BR for Brassica chinensis; PN for Pharbitis nil; RS for Raphanus sativus; AB for Ammannia baccifera; MV for
Monochoia vaginalis; BO for Brassica oleracea; BC for Brassica campestris; CA for Chenopodium album; BJ for Brassica juncea; /, not tested.
Table 4. Crop Selectivity of the Title Compounds IIa−g and IIr
a
crops (percent inhibition, postemergence)
compound
dosage (g ai/ha)
rice
corn
cotton
soybean
rape
wheat
IIa
IIb
IIc
IId
IIe
IIf
150
150
150
150
150
150
150
150
10 1.5
0
30 2.0
30 1.0
40 1.0
20 5.0
20 3.5
30 1.0
30 2.5
40 2.5
0
40
0
0
40
40 2.5
40
0
10 1.0
10 2.0
10 1.0
0
30
0
10
0
0
10 2.0
30 3.0
20 2.5
30 1.5
30 2.0
20 5.0
0
10
20 1.0
30
10 2.0
0
0
0
0
0
40 4.0
50 2.5
0
20
0
10
10
0
0
0
IIg
IIr
0
20 1.5
20 3.0
40
0
40 5.0
a
>10%, not safe to crops; 0−10%, safe to crops.
notable herbicidal activity against all tested broadleaf weeds
with 85−100% inhibition effect. However, they were almost
inactive against monocot weeds.
Comparing herbicidal activity among the title compounds
IIa−s in Table 1, the title compounds with 2,4-Cl2 or 2-CH3, 4-
Cl as X and Y (such as IIa−g, IIk, IIo, and IIr), exhibit
significant herbicidal activity against tested dicotyledons for
postemergence at a dosage of 150 g ai/ha, irrespective of
different substituents in the R moiety (such as CH3, 2-furyl, Ph,
2,4-Cl2−Ph, 4-Cl−Ph, i-Pr, and n-Bu).
On the basis of the preliminary bioassays, the title
compounds with 2,4-Cl2 and 2-CH3, 4-Cl as X and Y were
selected for further bioassay at lower dose for postemergence
herbicidal activity. The subsequent results in Table 2 show that
the title compounds IIa-c, IIf, IIg, and IIr have an herbicidal
activity comparable to that of compound I-1 (HW02) against
B. juncea with >90% inhibition in a dosage of 75 g ai/ha, and it
can be found that the title compound IIr with 2-CH3, 4-Cl as X
and Y has the most effective inhibition against all tested
broadleaf weeds, even at a dosage as low as 37.5 g ai/ha.
Comparing the title compound IIr with compound I-2, both
with 2-CH3, 4-Cl as X and Y, however, the title compound IIr
containing phosphorus-heterocyclic ring exhibits much higher
herbicidal activity than that of compound I-2. From the data in
Table 1, the compound I-2 displays very poor herbicidal
activity against B. juncea, A. retroflexus, and E. prostrate at a dose
of 150 g ai/ha, and it has almost no herbicidal activity at a lower
dose. This finding illustrates that the herbicidal activity of the
compound can be greatly enhanced by replacement of MeO
group attached to phosphorus moiety in the structure I with a
phosphorus-containing heterocyclic ring when keeping 2-CH3,
4-Cl as X and Y. Also, it has come to our notice that the
herbicidal activity of the title compound IIr against A.
retroflexus and E. prostrate seems also better than the compound
I-1 (HW02). Besides, the introduction of 2,4-Cl2−Ph or 4-Cl−
Ph as R results in a decrease in herbicidal activity when 2,4-Cl2
is kept constant as X and Y; for example, the title compounds
IId and IIe are very weak or inactive against tested broadleaf
weeds at a dosage of 37.5 or 75 g ai/ha.
Structure−activity relationship analysis indicates that the
introduction of a phosphorus-containing heterocyclic ring
seems to have a favorable effect on herbicidal activity, and
substituents X and Y on the benzene ring still greatly affect
activity. However, it is noteworthy that the title compounds II
with 2-CH3, 4-Cl as X and Y show higher or the same herbicidal
activity as compared to those of compounds containing 2,4-Cl2
as X and Y, such as compound I-1 (HW02) and the title
compound IIa. This finding is much different from SAR
analyses for compounds I.19
Novel herbicides must possess broad spectrum and high
activities against weeds. Hereby, some of the title compounds
IIa, IIb, and IIr were chosen for a broad spectrum test to
confirm their activity and potential application as novel
herbicides using A. retroflexus, B. chinensis, P. nil, R. sativus, A.
baccifera, M. vaginalis, B. oleracea, B. campestris, C. album, and B.
juncea. The results in Table 3 show the herbicidal activity and
spectrum of the title compounds IIa, IIb, and IIr are
comparable with glyphosate. Especially, the title compounds
IIa, IIb, and IIr show higher herbicidal activity than glyphosate
against P. nil, R. sativus, B. oleracea, and B. juncea at a dosage of
75 g ai/ha.
In addition, we also tested the crop selectivity of the title
compounds (IIa−g and IIr) as shown in Table 4. The title
compounds IIa, IIe, and IIr have a higher level of selectivity for
corn and wheat by postemergence application at the dosages of
150 g ai/ha among the eight tested compounds, thus indicating
that further development could be carried out for purposes of
weed control in corn or wheat fields.
7586
dx.doi.org/10.1021/jf301829m | J. Agric. Food Chem. 2012, 60, 7581−7587

Journal of Agricultural and Food Chemistry
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AUTHOR INFORMATION
■
Corresponding Author
*Tel./fax: +86-27-67867960. E-mail: he1208@mail.ccnu.edu.cn
(H.-W.H.), penghao@mail.ccnu.edu.cn (H.P.).
(18) Peng, H.; Wang, T.; Xie, P.; Chen, T.; He, H. W.; Wan, J.
Molecular docking and three-dimensional quantitative structure−
activity relationship studies on the binding modes of herbicidal 1-
(substituted phenoxyacetoxy)alkylphosphonates to the E1 component
of pyruvate dehydrogenase. J. Agric. Food Chem. 2007, 55, 1871−1880.
(19) 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. Studies of O,O-dimethyl
α-(2,4-dichlorophenoxyacetoxy)ethylphosphonate (HW02) as a new
herbicide. 1. synthesis and herbicidal activity of HW02 and analogues
as novel inhibitors of pyruvate dehydrogenase complex. J. Agric. Food
Chem. 2011, 59, 4801−4813.
Funding
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
(No.2011BAE06B03), and the National Natural Science
Foundation of China (No. 21172090). This research was
supported in part by the PCSIRT (No. IRT0953).
Notes
The authors declare no competing financial interest.
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