The synthesis and herbicidal evaluation of fluorine-containing phenoxyacetoxyalkylphosphonate derivatives

Article abstract of DOI:10.1080/10426500600614253

To investigate the influence of a fluorine moiety on the biological activity of phenoxyacetoxyalkylphosphonates, a series of fluorine-containing phenoxyacetoxyalkylphosphonates were synthesized and screened for herbicidal activity in a greenhouse. The majority of the title compounds showed better preemergence activity than postemergence activity against the test plants, especially on monocotyledon. Compound 5l exhibited notable activity. Results showed that by introducing a fluorine moiety to the parent structure of phenoxyacetoxyalkylphosphonates, a series of new compounds with satisfactory herbicidal activity could be synthesized. A reasonable combination of a fluorine moiety and other substituents on the benzene ring had a great influence on the herbicidal activity. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500600614253

Phosphorus, Sulfur, and Silicon, 181:2135–2145, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600614253
The Synthesis and Herbicidal Evaluation
of Fluorine-Containing Phenoxyacetoxyalkylphosphonate
Derivatives
Ting Chen
Ping Shen
Yanjun Li
Hongwu He
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education,
Institute of Pesticide Chemistry, Central China Normal University,
Wuhan, People’s Republic of China
To investigate the influence of a fluorine moiety on the biological activity of phenoxy-
acetoxyalkylphosphonates, a series of fluorine-containing phenoxyacetoxyalkylphos-
phonates were synthesized and screened for herbicidal activity in a greenhouse. The
majority of the title compounds showed better preemergence activity than postemer-
gence activity against the test plants, especially on monocotyledon. Compound 5l ex-
hibited notable activity. Results showed that by introducing a fluorine moiety to the
parent structure of phenoxyacetoxyalkylphosphonates, a series of new compounds
with satisfactory herbicidal activity could be synthesized. A reasonable combina-
tion of a fluorine moiety and other substituents on the benzene ring had a great
influence on the herbicidal activity.
Keywords 1-hydroxyl alkylphosphonate; fluorophenoxyacetic acid; herbicidal activity;
synthesis
INTRODUCTION
Fluorine is a very unique element with special biomimetic, high thermal
stability and lipophilicity, which endows various prominent functional-
ity in the organofluorine compounds. By introducing a fluorine atom
into organic molecules, we can get compounds with improved physical,
Received November 20, 2005; accepted December 20, 2005
We gratefully acknowledge financial support of this work by the National Basic Re-
search Program of China (2003CB114400) and the National Natural Science Foundation
of China (Project No. 20372023).
Address correspondence to Hongwu He, Institute of Pesticide Chemistry, Central
China Normal University, Wuhan, 430079, People’s Republic of China. E-mail: he1208@
mail.ccnu.edu.cn
2135

2136
T. Chen et al.
FIGURE 1 The general structure of 1-substituted phenoxyacetoxyalkylphos-
phonates.
chemical, and biological properties.1−3 So the application of fluorides in
pharmaceuticals and pesticides attracted more and more attention.
In our group, a recent study on 1-oxophosphonic acid derivatives
revealed that 1-oxophosphonic acid derivatives, which possessed good
herbicidal activities, could act as a leading structure for herbicide de-
signing. The general structure (1) is shown in Figure 1. Structure mod-
ification has been attempted by introducing different substituents X
and Y to the benzene ring.4,5 But none of our previous work was de-
voted to the synthesis of fluorosubstituted phenoxyacetoxyalkylphos-
phonates, neither systematic structure-activity study of the this kind
of compounds. So the fluorine moiety was introduced to the core struc-
ture (1) as a continued research of our previous work, and a novel series
of O,O-dialkyl 1-(fluorophenoxyacetoxy)alkylphosphonates 5a–m were
synthesized and screened for herbicidal activity.
RESULTS AND DISCUSSION
Chemistry
Compound 1 could be easily synthesized starting from fluorophenol and
bromoacetic ester.6 Dimethyl phosphite and diethyl phosphite were ob-
tained by the reported method,7 and compound 4 could be prepared by
the reaction of compound 3 and several kinds of aldehydes using potas-
sium fluoride and alumina (mass ratio was 1:1) as a catalyst in a yield
of 65–94% according to the literature.8,9
The preparation of title compounds involved the condensation
of fluorophenoxyacetyl chloride 2 and O,O-dimethyl 1-hydroxylal-
kylphosphonates or O,O-diethyl 1-hydroxylalkylphosphonates 4. The
synthetic pathway is outlined in Scheme 1, and the structures of 5a–m
are given in Table I.
The title compounds contained carboxylic ester bond which was sen-
sitive to acid, base, and water, so the reaction required a temperature
near r.t. and the reagent in anhydrous chloroform or dichoromethane.
All new compounds were identified by 1H NMR, IR, MS, and elemen-
tal analysis. All the main functional groups were characterized in IR

Phenoxyacetoxyalkylphosphonate Derivatives
2137
SCHEME 1
spectra. A strong absorption near 1760 cm−1 was identified for the ab-
sorption C O. A sharp and weak band at 3050–3100 cm−1 accounted for
the C H stretching of the benzene ring and a strong peak at 1260 cm−1
for P O stretching. Another strong peak at 1330 cm−1 was the evidence
for the Ar-CF3 symmetry stretching. Doublets near 6.40 ppm confirmed
the existence of O-CHP. The coupling constant of J was 13.2 Hz.
PH
Biological Assays
Herbicidal Activity Tests in Greenhouse
The herbicidal activities of title compounds 5a–m were evaluated
at a rate of 1.5 a.i. kg/ha in a set of an experiment in a greenhouse.
TABLE I The Preparation of O,O-Dialkyl 1-(Fluorophenoxyacetoxy)
alkylphosphonates 5a–m
Compound
X
Y
R1
R2
Condition
Yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
H
H
H
H
H
H
H
H
H
H
H
2-Cl
2-Cl
3-CF3
3-CF3
3-CF3
3-CF3
3-CF3
3-CF3
3-CF3
4-F
CH3
C2H5
CH3
C2H5
C2H5
C2H5
C2H5
CH3
CH3
CH3
CH3
CH3
CH3
2,4-2ClPh
2,4-2ClPh
3,4-2ClPh
3,4-2ClPh
2-ClPh
3-NO2Ph
Ph
3-NO2Ph
Ph
CH3
2 h/20◦C
3 h/20◦C
2 h/20◦C
3 h/20◦C
3 h/20◦C
3 h/20◦C
3 h/20◦C
2 h/20◦C
2 h/20◦C
2 h/20◦C
2 h/20◦C
2 h/20◦C
2 h/20◦C
65.3
52.8
73.2
79.2
65.4
78.5
76.1
63.5
73.1
69.0
66.5
86.5
72.5
4-F
5j
5k
5l
4-CF3
4-CF3
4-F
CCl3
CH3
CCl3
5m
4-F

2138
T. Chen et al.
They were tested for a preemergence and postemergence inhibitory
effect against Echinochloa Crusgalli Beava (barngard grass), Dig-
itaria Sanguinalis scop (ascendant crabgrass), Brassica napus L.
(rape), Amaranthus retroflerus L. (amaranth), and Medicago sativa
L. (clover). Plastic pots were packed with sandy clay loam soil, and
water was added up to 3 cm in depth. Fifteen to twenty seeds were
sown in the soil at a depth of 5 mm and grown at 20–25◦C for a
few days. At the preemergence and postemergence, the diluted for-
mulation of each compound containing acetone and Tween 80 were
applied into the pots at 1.5 a.i. kg/ha. Twenty days later, the pre-
emergence herbicidal activity against each weed was visually evalu-
ated. At the postemergence, the solution of the chemicals tested was
applied to the foliage of plants grown at 2 to 3 leaves stage with a
sprayer at the rate of 1.5 a.i. kg/ha and with a spelling volume of
1000 L/ha. All treatments were replicated three times in a completely
randomized design. Test plants were harvested 20 days after sowing,
were determined for fresh weight, and were evaluated for postemer-
gence herbicidal activity. The percentage growth inhibition of roots
and aerial parts were calculated in relation to the mass of the roots
and aerial parts of the control, respectively. The results are listed in
Table II.
TABLE II The Herbicidal Activity of Title Compounds (1.5 a.i. kg/ha,
Relative Inhibition of Growth %)
Ech.a
Dig.
Pre
Bra.
Ama.
Post
Med.
Pre
Compound Pre Post
Post Pre Post
Pre
Post
16.2
100
76.6
100
100
83.3
100
38.9
49.4
26.0
14.3
92.2
88.3
5a
5b
5c
5d
5e
5f
5g
5h
5i
34.7
9.9
56.7
63.8
6.4
97.9
97.9
97.9
4.4 55.1 75.0
25.3
86.4
100
24.1
89.9
100
93.2
100
100
100
52.1
60.4
8.3
0
97.9
95.8
21.6 30.6
54.9 25.0
48.0 30.6
75.5 8.3
88.3
90.2 51.4 100
0
0
44.0
88.5
92.3
96.2
16.0 80.3 36.2 100
20.0 37.4 49.6
36.0 16.1 43.3
72.3
68.2
100
0
32.0 33.9 61.7 100
84.6
84.6
79.1
77.5
63.1
71.1
16.0 43.3 83.7
55.2 16.6 44.8
45.1 48.3 56.7
12.6 17.9 28.8
91.0
64
31.0
76.7
84.5
10.1
14.7
38.9
63.9
0
0
97.2
86.1
55.9 50.7
0
0
94.8 76.1 100
87.5 68.5 95.4
5j
5k
5l
34.3
10.3
0
15.9 21.0
67.5 96.9 82.4
60.8 95.9 79.4
100
100
5m
aEch: Echinochloa Crusgalli Beava; Dig: Digitaria Sanguinalis scop; Bra: Brassica
napus L. Ama: Amaranthus retroflerus L.; Med: Medicago sativa
Post: postemergence; Pre: preemergence.

Phenoxyacetoxyalkylphosphonate Derivatives
2139
IC50 Values Test
Based on the preliminary bioassays, title compounds were tested
for IC50 values against the preemergence growth of Cucumis sativa
L. at different concentrations by the following method. A compound
with a certain concentration was dissolved in acetone and placed on a
filter paper (5.5 cm diameter) in Petri dishes (9 cm), and 10 cucumber
(Cucumis sativa L.) seeds (Jinyan 4) were placed on the filter paper
after soaking in water for 6 h. The Petri dishes with cucumber seeds
were placed in a LRH-250-G lighting culture tank at 28◦C for 3 days
with 10 h of lighting and 14 h in the dark. After 3 days of cultivation,
the inhibition percentage was calculated by the corresponding control
using the length of the taproot as an indicator. The concentrations were
24.0, 12.0, 6.0, 3.0, and 1.5 µg g−1 for compounds 5b, 5c, 5d, and 5e;
18.0, 7.2, 2.88, and 1.152 µg g−1 for compounds 5f and 5g; 4.0, 2.0, 1.0,
0.5, and 0.25 µg g−1 for compound 5h; 2.0, 1.0, 0.5, 0.25, and 0.125 µg
g−1 for compound 5i; 240.0, 160.0, 106.67, 71.11, and 47.41 µg g−1 for
compound 5j; 800.0, 400.0, 200.0, 100.0, and 50.0 µg g−1 for compound
5k; 0.5, 0.25, 0.125, 0.0625, and 0.01325 µg g−1 for compound 5l; and 1.0,
0.5, 0.25, 0.125, and 0.0625 µg g−1 for compound 5m. Three replications
per concentration were performed. According to the average inhibition
of cucumber root at five concentration for each test compound, IC50 was
estimated by regression analysis using a logarithm of concentration and
a probit of corresponding inhibition percentage. The results of bioassay
are listed in Table III. As there was not enough sample for compound
5a, only 12 results were listed.
As Table II indicates, there were remarkable differences among the
herbicidal activity of the title compounds, and they showed accept-
able herbicidal activity except for compounds 5h, 5i, 5j, and 5k.
The majority of title compounds showed better preemergence activity
TABLE III The IC50 of Title Compounds Against Cucumis sativa L.
Regression
Equation
Regression
Equation
No.
IC50 (µg g−1
)
No.
IC50 (µg g−1
)
5b Y = 4.44 + 0.91x 4.14 (4.01–4.27) 5h Y = 5.15 + 0.10x 0.73 (0.60–0.86)
5c Y = 4.46 + 0.89x 4.04 (3.93–4.15) 5i Y = 5.15 + 1.22x 0.75 (0.68–0.82)
5d Y = 4.28 + 0.82x 7.58 (7.40–7.70) 5j Y = 0.85 + 2.14x 87.94 (87.81–88.07)
5e Y = 4.47 + 0.94x 3.68 (3.56–3.76) 5k Y = 1.18 + 1.83x 119.92 (119.02–119.28)
5f
Y = 4.53 + 0.72x 4.56 (4.35–4.64) 5l Y = 6.45 + 1.43x 0.10 (0.02–0.21)
5g Y = 4.59 + 0.81x 3.19 (3.00–3.25) 5m Y = 5.99 + 1.10x 0.13 (0.055–0.20)
aIC50 value is defined as the micromolar concentration required for 50% inhibition in
the growth of a root length of Cucumber (Cucumis sativa L.)
bThe fiducial limit was 95%.

2140
T. Chen et al.
than postemergence activity against the test plants especially on mono-
cotyledon, such as compounds 5l, and 5m, 5f, and 5g exhibited no-
table preemergence inhibitory effects against 5 plants species and
4 plants species, except Brassica napus L., respectively, and com-
pounds 5d and 5e also exhibited good preemergence inhibitory ef-
fects against Digitaria Sanguinalis scop. On the other hand, the title
compounds showed better postemergence activity on dicotyledon than
monocotyledon. Compounds 5a, 5b, 5c, 5g, and 5m exhibited ob-
vious postemergence inhibitory effects (>90%) against Amaranthus
retroflerus L. or Medicago sativa, especially compounds 5d, 5e, and
5l, which exhibited 92–100% inhibitory effects against both Amaran-
thus retroflerus L. and Medicago sativa. According to the IC50 value
shown in Table III, compounds 5l and 5m, for which the IC50 were
0.10 and 0.13 µg g−1, respectively, displayed higher inhibitory ac-
tivity, whereas 5j and 5k, for which the IC50 were 87.94 µg g−1
and 119.92 µg g−1, respectively, displayed lower inhibitory activity
against the growth of the root of Cucumis sativa L. The IC50 results
well corresponded to the results in Table II except for compounds
5h and 5i, which showed much better inhibitory activity against the
growth of Cucumis sativa L. than other test dicotyledon. As seen
from Table II, compounds 5l and 5m exhibited higher inhibitory ac-
tivity, whereas 5j and 5k exhibited lower inhibitory activity, of only
0–28% against the test plants except for the postemergence inhibition
against Amaranthus retroflerus in 63.1% and 71.3%, respectively, in the
greenhouse.
Among all the compounds, compound 5l showed the highest activity,
which exhibited 94.8–100% preemergence inhibitory activity against
all the test plants, 92.2–100% post-emergence inhibition against both
Amaranthus retroflerus L. and Medicago sativa, and 67–82% post-
emergence inhibition against other test plants. Its IC50 value also
showed the highest activity against the growth of the root of Cucumis
sativa L.
We found the structure of substituents X and Y in the benzene ring
had great influence on the herbicidal activity: such herbicidal activity
could be enhanced by introducing 2-Cl-4-F to the benzene ring, whereas
the introduction of X and Y as 1-H-4-CF3 resulted in a sharp decrease
in their herbicidal activity toward test plants. As a typical example, the
herbicidal activity of compounds 5l and 5m (X and Y as 2-Cl-4-F, R1 as
CH3, R2 as CH3 or CCl3) was much higher than that of compounds 5j
and 5k (X and Y as 1-H-4-CF3, R1 as CH3, R2 as CH3 or CCl3) and also
higher than others. So we can conclude that the herbicidal activity of
title compounds highly depends upon the structure of the substituents
on the benzene ring.

Phenoxyacetoxyalkylphosphonate Derivatives
2141
In conclusion, a series of new compounds with satisfactory herbici-
dal activity could be attained by the introduction of a fluorine moiety. A
reasonable combination of a fluorine moiety and other substituents had
great influence on their herbicidal activity. These results provided some
interesting hints for further study of the structure modification and
structure-activity relationship of this kind of phenoxyacetoxyalkylphos-
phate derivatives.
EXPERIMENTAL
Mass spectra were measured on a Finnigan Trace MS 2000 spectrom-
eter. Infrared spectra were recorded in potassium bromide disks on a
Nicolet Avatar360 FTIR spectrometer. 1H NMR was recorded in deute-
rocholroform solution at 400 MHz using tetramethysilane as internal
standard on Varian Mercury-Plus 400 spectrometer. Elemental analy-
sis was performed by an Elementar Vario EL III elementary analyzer.
Melting points (m.p.) were measured on an electrothermal melting-
point apparatus, and the temperature was uncorrected.
The General Synthetic Procedure for 1 and 2
To a three-neck boiling flask, fluorophenol (40 mmol), bromoacetic es-
ter (7.01 g, 42 mmol), and potassium carbonate (6.0 g, 43.5 mmol) were
added by order; then anhydrous DMSO (150 mL) was added. The mix-
ture was stirred and kept at 70–80◦C for 5 h and then was treated with
ice water immediately. After the yellow solid was filtered off and dis-
solved in acetone (20 mL), sodium hydrate (2 mol/L, 30 mL) was added
and then stirred for another 2 h at r.t. Then hydrochloric acid (2 mol/L,
30 mL) was added, and the fluorophenoxyacetic acid 1 formed. The solid
can be recrystalized as a white crystal in a yield of 70%. The correspond-
ing fluorophenoxyacetyl chloride 2 can be easily obtained as a yellow
liquid in a 90% yield by treating compound 1 with thionyl chloride.
The General Synthetic Procedure for 4
Dimethyl phosphite (1.38 g, 10 mmol) or diethyl phosphite 3 (1.10 g,
10 mmol) and several kinds of aldehydes (10 mmol) were stirred at r.t.
for 10 min; then potassium fluoride and alumina (mass ratio was 1:1,
3 g) were added. The mixture was stirred for another 30 min, dissolved
in dichoromethane (15 mL), and filtered. Dichoromethane was evapo-
rated under reduced pressure, and the products were formed as white
solids or a colorless liquid in a yield of 65–94%.

2142
T. Chen et al.
The General Synthetic Procedure for 5a–m
solution of fluorophenoxyacetyl chloride
A
2
(5.2 mmol) in
trichloromethane (10 mL) was added dropwise to stirred mixture
of 1-hydroxyalkylphosphonate 4 (5 mmol) and triethylamine (0.53 g,
5 mmol) in trichloromethane (15 mL) at 2∼4◦C. The resultant mixture
was stirred at an ambient temperature for 2∼3 h, washed with hy-
drochloric acid (0.1 mol/L, 25 mL), saturated sodium hydrate solution
(25 mL) and brine (25 mL) separately; dried; and evaporated. The
residue was chromatographed on silica with 20% acetone in petroleum
ether as an eluent to give 5a–m as a yellow liquid or white solid.
O,O-Dimethyl1-(3-trifluoromethylphenoxyacetoxy)2,4-
dichlorobenzylphosphonate (5a)
Yellow liquid, n2D0 1.5221; H NMR (400 MHz, CDCl3): δ 3.58–3.71
1
(d, 6H, J = 9.7 Hz, 2OCH3), 4.74 (s, 2H, OCH2CO), 6.40–6.42 (d,
HP
1H, J = 13.3 Hz, OCHP), 7.01–7.40 (m, 7H, C6H4, C6H3); IR (νmax
,
HP
cm−1): 3076 (Ar-H), 1754 (C O), 1330 (Ar-CF3), 1265 (P O), 742 (P C);
EIMS (probe) 70 eV, m/z (rel. int.): 93 (76), 125 (42), 127 (43), 175 (94),
255 (100), 487 (33); anal. calcd. for C18H16O6PF3Cl2: C, 44.35; H, 3.29.
Found: C, 44.60; H, 3.31%.
O,O-Diethyl 1-(3-trifluoromethylphenoxyacetoxy)2,4-
dichlorobenzylphosphonate (5b)
Yellow liquid, n2D0 1.5139; H NMR (400 MHz, CDCl3): δ 1.18–1.30
1
(m, 6H, J = 7.0 Hz, 2OCH2CH3), 3.94–4.10 (m, 4H, J = 7.2 Hz,
HH
2O CH2CH3), 4.78 (s, 2H, OCH2CO), 6.60–6.63 (d, 1H, JHH= 13.3 Hz,
HP
OCHP), 7.04–7.47 (m, 7H, C6H4, C6H3); IR (νmax, cm−1): 3079 (Ar-H),
1758 (C O), 1331 (Ar-CF3), 1266 (P O), 742 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 93 (82), 121 (100), 145 (94), 173 (96), 231 (65), 516 (5.8);
anal. calcd. for C20H20O6PF3Cl2: C, 46.60; H, 3.88. Found: C, 46.50; H,
3.99%.
O,O-Dimethyl 1-(3-trifluoromethylphenoxyacetoxy)
3,4-dichlorobenzy phosphonate (5c)
Yellow liquid, n2D0 1.5320; H NMR (400 MHz, CDCl3): δ 3.50–3.58
1
(d, 6H, J = 10.2 Hz, 2OCH3), 4.49 (s, 2H, OCH2CO), 6.50–6.64 (d,
HP
1H, J = 13.2 Hz, OCHP), 7.04–7.42 (m, 7H, C6H4, C6H3); IR (νmax
,
HP
cm−1): 3079 (Ar-H), 1775 (C O), 1333 (Ar-CF3), 1267 (P O), 742 (P C);
EIMS (probe) 70 eV, m/z (rel. int.): 93 (95), 109 (74), 127 (47), 145 (81),
175 (100), 486 (2.6); anal. calcd. for C18H16O6PF3Cl2: C, 44.35; H, 3.29.
Found: C, 44.85; H, 3.48%.

Phenoxyacetoxyalkylphosphonate Derivatives
2143
O,O-Diethyl 1-(3-trifluoromethylphenoxyacetoxy)
3,4-dichlorobenzylphosphonate (5d)
Yellow liquid, n2D0 1.5159; H NMR (400 MHz, CDCl3): δ 1.10–1.30
(m, 6H, J = 7.2 Hz, 2OCH2CH3), 3.99–4.22 (m, 4H, J = 7.0 Hz,
1
HH
HH
2O CH2CH3), 4.78 (2H, OCH2CO), 6.09–6.10 (d, 1H, J = 13.3 Hz,
HP
OCHP), 7.00–7.40 (m, 7H, C6H4, C6H3); IR (νmax, cm−1): 3075 (Ar-H),
1777 (C O), 1330 (Ar-CF3), 1264 (P O), 740 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 121 (100), 145 (92), 175 (83), 516 (80); anal. calcd. for
C20H20O6PF3Cl2: C, 46.60; H, 3.88. Found: C, 46.58; H, 3.93%.
O,O-Diethyl 1-(3-trifluoromethylphenoxyacetoxy)
2-chlorobenzylphosphonate (5e)
Yellow liquid, n2D0 1.4932; H NMR (400 MHz, CDCl3): δ 1.28–1.30
1
(m, 6H, J = 6.9 Hz, 2OCH2CH3), 3.91–4.20 (m, 4H, J = 7.0 Hz,
HH
HH
2O CH2CH3), 4.75 (2H, OCH2CO), 6.71–6.73 (d, 1H, J = 13.3 Hz,
HP
OCHP), 7.02–7.54 (m, 8H, 2C6H4); IR (νmax, cm−1): 3070 (Ar-H), 1750
(C O), 1333 (Ar-CF3), 1263 (P O), 742 (P C); EIMS (probe) 70 eV, m/z
(rel. int.): 108.9 (82), 121 (100), 138 (98), 175 (94), 197 (85), 480 (4.5);
anal. calcd. for C20H21O6PF3Cl: C, 49.95; H, 4.37. Found: C, 49.392; H,
4.42%.
O,O-Diethyl 1-(3-trifluoromethylphenoxyacetoxy)3-
nitrobenzylphosphonate (5f)
1
Yellow solid, m.p. 86.7–87.7◦C; H NMR (400 MHz, CDCl3): δ 1.23–
1.30 (m, 6H, JHH = 7.0 Hz, 2OCH2CH3), 3.80–4.20 (m, 4H, J = 7.2 Hz,
2OCH2CH3), 4.77 (s, 2H, OCH2CO), 6.50–6.60 (d, 1H, J H=H 13.3 Hz,
HP
OCHP), 7.05–7.36 (m, 8H, 2C6H4); IR (νmax, cm−1): 3074 (Ar-H), 1761
(C O), 1335 (Ar-CF3), 1250 (P O), 742 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 121 (100), 145 (91), 175 (98), 491 (49); anal. calcd. for
C20H21O8PF3N: C, 48.88; H, 4.28; N, 2.85. Found: C, 48.55; H, 4.06; N,
2.63%.
O,O-Diethyl 1-(3-trifluoromethylphenoxyacetoxy)
benzylphosphonate (5g).
1
White solid, m.p. 92.5–93.6◦C; H NMR (400 MHz, CDCl3): δ 1.18–
1.24 (m, 6H, JHH = 7.4 Hz, 2OCH2CH3), 3.90–4.07 (m, 4H, J = 7.2 Hz,
2OCH2CH3), 4.74 (s, 2H, OCH2CO), 6.70–6.74 (d, 1H, J H=H 13.2 Hz,
HP
OCHP), 7.04–7.30 (m, 9H, C6H4, C6H5); IR (νmax, cm−1): 3076 (Ar-H),
1770 (C O), 1330 (Ar-CF3), 1267 (P O), 743 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 121 (100), 145 (85), 175 (98), 446 (15); anal. calcd. for
C20H22O6PF3: C, 53.81; H, 4.93. Found: C, 53.59, H, 4.61%.

2144
T. Chen et al.
O,O-Dimethyl 1-(4-fluorophenoxyacetoxy)
3-nitrobenzylphosphonate (5h)
Yellow liquid (63.5% yield): n2D0 1.5225; 1H NMR (400 MHz, CDCl3):
δ 3.70–3.81 (d, 6H, J = 9.7 Hz, 2OCH3), 4.78 (s, 2H, OCH2CO), 6.32–
HP
6.34 (d, 1H, J = 13.1 Hz, OCHP), 6.85–7.42 (m, 8H, C6H4); IR (νmax
,
HP
cm−1): 3080 (Ar-H), 1767 (C O), 1260 (P O), 742 (P C); EIMS (probe)
70 eV, m/z (rel. int.): 93 (100), 109 (98), 151 (63), 170 (97), 261 (66), 413
(6); anal. calcd. for C17H17O8PNF: C, 49.40; H, 4.15; N, 3.39, Found: C,
50.08; H, 4.35; N, 3.18%.
O,O-Dimethyl 1-(4-fluorophenoxyacetoxy)
benzylphosphonate (5i).
Yellow solid, m.p. 131.1–131.3◦C; 1H NMR (400 MHz, CDCl3): δ 3.62–
3.72 (d, 6H, J = 10.4 Hz, 2OCH3), 4.72 (s, 2H, OCH2CO), 6.26–6.34
HP
(d, 1H, JHP = 13.2 Hz, OCHP), 6.88–7.42 (m, 9H, C6H5, C6H4); IR (νmax
,
cm−1): 3077 (Ar-H), 1770 (C O), 1263 (P O), 735 (P C); EIMS (probe)
70 eV, m/z (rel. int.): 93 (99), 109 (100), 151 (11), 170 (98), 199 (80), 216
(27), 368 (18); anal. calcd. for C17H18O6PF: C, 55.44; H, 4.93. Found: C,
55.12; H, 4.70%.
O,O-Dimethyl 1-(4-trifluoromethylphenoxyacetoxy)
ethylphosphonate (5j)
‘Yellow liquid, n2D0 1.4609; 1H NMR (400 MHz, CDCl3): δ 1.50–
1.51 (dd, 3H, J = 7.1 Hz, J = 13.3 Hz, CH3), 3.76–3.84 (d, 6H,
HH
HP
J
= 10.0 Hz, 2OCH3), 4.75 (s, 2H, OCH2CO), 5.39–5.43 (m, 1H, J
=
HP
HH
7.1 Hz, J = 13.3 Hz, OCHP), 6.97–7.58 (m, 4H, C6H4); IR (νmax, cm−1):
HP
3087 (Ar-H), 1769 (C O), 1330 (Ar-CF3), 1271 (P O), 742 (P C); EIMS
(probe) 70 eV, m/z (rel. int.): 79 (45), 93 (98), 109 (100), 138 (98), 195
(62), 356 (40); anal. calcd. for C13H16O6PF3: C, 43.83; H, 4.53. Found:
C, 43.97; H, 4.28%.
O,O-Dimethyl 1-(4-trifluoromethylphenoxyacetoxy)
trichloromethylmethylphosphonate (5k)
Yellow liquid, n2D0 1.4850; H NMR (400 MHz, CDCl3): δ 3.76–3.91
1
(d, 6H, J = 10.0 Hz, 2OCH3), 4.90 (s, 2H, OCH2CO), 5.89–5.96 (d,
HP
1H, J = 13.2 Hz, OCHP), 6.94–7.56 (m, 4H, C6H4); IR (νmax, cm−1):
HP
3081 (Ar-H), 1786 (C O), 1330 (Ar-CF3), 1271 (P O), 742 (P C); EIMS
(probe) 70 eV, m/z (rel. int.): 79 (63), 93 (75), 109 (82), 139 (15), 175 (100),
458 (27); anal. calcd. for C13H13Cl3O6PF3: C, 33.98; H, 2.85. Found: C,
33.89; H, 2.76%.

Phenoxyacetoxyalkylphosphonate Derivatives
2145
O,O-Dimethyl 1-(2-chloro-4-fluorophenoxyacetoxy)
ethylphosphonate (5l)
White solid, m.p. 118.9–120.1◦C; 1H NMR (400 MHz, CDCl3): δ 1.48–
1.54 (dd, 3H, J = 7.1 Hz, J = 13.1 Hz, CH3), 3.78–3.86 (d, 6H, J
HH
HP
HP
= 10.4 Hz, 2OCH3), 4.72 (s, 2H, OCH2CO), 5.40–5.43 (m, 1H, J
=
HH
7.1 Hz, JHP =13.1 Hz, OCHP), 6.84–7.27 (m, 3H, C6H3); IR (νmax, cm−1):
3081(Ar-H), 1750 (C O), 1263 (P O), 742 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 79 (43), 93 (85), 109 (100), 138 (99), 195 (49), 340 (75);
anal. calcd. for C12H15ClO6PF: C, 42.31; H, 4.44. Found: C, 42.29; H,
4.44%.
O,O-Dimethyl 1-(2-chloro-4-fluorophenoxyacetoxy)
trichloromethylmethylphosphonate (5m)
White solid, m.p. 104–105.2◦C; 1H NMR (400 MHz, CDCl3): δ 3.86–
3.90 (d, 6H, J = 10.2 Hz, 2OCH3), 4.91 (s, 2H, OCH2CO), 5.40–5.44
HP
(d, 1H, JHP = 13.3 Hz, OCHP), 6.91–7.27 (m, 3H, C6H3); IR (νmax, cm−1):
3089 (Ar-H), 1779 (C O), 1266 (P O), 742 (P C); EIMS (probe) 70 eV,
m/z (rel. int.): 79 (56), 93 (82), 109 (100), 159 (94), 205 (57), 442 (17);
anal. calcd. for C12H12Cl4O6PF: C, 32.46; H, 2.72. Found: C, 32.65; H,
2.55%.
REFERENCES
[1] J. T .Welch, Tetrahedron. 43, 3123 (1987).
[2] M. Hudlicky, Chemistry of Organic Fluorine Compounds II, pp. 1119–1121 (American
Chemical Society, Washington, DC, 1995).
[3] V. P. Kukhar, J. Fluorine Chem., 69, 199 (1994).
[4] H. W. He and Z. J. Liu, Chin. J. Org. Chem., 21, 878 (2001).
[5] H. W. He, X. F. Liu, and Z. J. Liu, Phosphorus, Sulfur, and Silicon, 1, 144 (1999).
[6] J. L. Brayer, L. Talinani, and J. Tessier, Eur. Pat. Appl. (EP), 376819 (1990).
[7] H. Mccommbie and B. C. Sauaders, J. Chem. Soc., 2, 380 (1945).
[8] F. Texier-Boullet and M. Leouitte, Tetrahedron Lett., 27, 3515 (1986).
[9] F. Texier-Boullet and A. Foucaud, Synthesis, 11, 916 (1982).