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

Article abstract of DOI:10.1016/j.jfluchem.2012.06.020

A series of novel 2-(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2- dioxaphosphinan-2-one bearing fluorine 5a-n and fluorine free 5o-q were designed and synthesized. The results of bioassay showed that some of the target compounds exhibited excellent herbicidal activities to Abutilon theophrasti, Brassica juncea, Amaranthus retroflexus and Eclipta prostrata in post-emergence treatment at a dosage of 150 g ai/ha. It could be found that the type and position of fluorine-containing group as X or Y on benzene ring had a very important effect on herbicidal activity. Compound 5l 2-[(2-chloro-4- fluorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one showed notable herbicidal activity, with 100% inhibition against A. theophrasti and A. retroflexus; and compound 5m 2-(3-trifluoromethylphenoxyacetoxy)(methyl) methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one with 100% inhibition against A. theophrasti even at a dosage of 75 g ai/ha. Additional crop selectivity testing showed that compounds 5g 2-(3-trifluoromethylphenoxyacetoxy)(phenyl)methyl-5,5- dimethyl-1,3,2-dioxaphosphinan-2-one and 5l are safe to rice, corn, cotton, rape and wheat.

Full text of DOI:10.1016/j.jfluchem.2012.06.020

Journal of Fluorine Chemistry 142 (2012) 24–28
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis and herbicidal activity of 2-(substituted phenoxyacetoxy)alkyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one containing fluorine
*
*
Wei Wang, Hong-Wu He , Na Zuo, Xin Zhang, Ji-Sheng Lin, Wei Chen, Hao Peng
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education; Institute of Pesticide Chemistry, College of Chemistry, Central China Normal University, Wuhan 430079,
PR China
A R T I C L E I N F O
A B S T R A C T
series of novel 2-(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one
Article history:
A
Received 26 April 2012
Received in revised form 5 June 2012
Accepted 12 June 2012
Available online 23 June 2012
bearing fluorine 5a-n and fluorine free 5o-q were designed and synthesized. The results of bioassay
showed that some of the target compounds exhibited excellent herbicidal activities to Abutilon
theophrasti, Brassica juncea, Amaranthus retroflexus and Eclipta prostrata in post-emergence treatment at a
dosage of 150 g ai/ha. It could be found that the type and position of fluorine-containing group as X or Y
on benzene ring had a very important effect on herbicidal activity. Compound 5l 2-[(2-chloro-4-
fluorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one showed notable
herbicidal activity, with 100% inhibition against A. theophrasti and A. retroflexus; and compound 5m
2-(3-trifluoromethylphenoxyacetoxy)(methyl)methyl-5,5-dimethyl-1,3,2-dioxaphosphinan-2-one
with 100% inhibition against A. theophrasti even at a dosage of 75 g ai/ha. Additional crop selectivity
testing showed that compounds 5g 2-(3-trifluoromethylphenoxyacetoxy)(phenyl)methyl-5,5-dimeth-
yl-1,3,2-dioxaphosphinan-2-one and 5l are safe to rice, corn, cotton, rape and wheat.
Keywords:
Synthesis
Herbicidal activity
Fluorine
Phosphonate
ß 2012 Elsevier B.V. All rights reserved.
1. Introduction
by the replacement of simple phosphonate moiety in parent
compound [9]. However, our previous work was not devoted to the
Due to unique properties of fluorine, such as the highest
electronegativity, smallest size next to hydrogen, high thermal
stability and lipophilicity, the substitution of hydrogen by fluorine
has become a common strategy in drug development [1,2]. A
variety of the reports regarding synthetic studies of organofluorine
compounds have been presented because they can increase the
herbicidal activity [3], fungicidal activity [4] and insecticidal
activity [5] of certain compounds. And a number of fluorinated
products (such as the herbicides flumioxazin, haloxyfop, flufenatet,
tritosulfuron, carfentrazone-ethyl and flumetsulam etc.) have been
launched into the market during the past decade (Scheme 1).
In our previous work, a series of 1-(substituted phenoxyace-
toxy)alkylphosphonates I (Scheme 2) have been synthesized,
which was confirmed as competitive inhibitors of pyruvate
dehydrogenase complex with notable herbicidal activities [2,6–
8]. The bioassay results showed that inhibitory potency of these
compounds could be greatly affected by the chemical modification
of R1, R2, R3, X and Y in structure I (Scheme 2). On the other hand, it
is well known that the introduction of cyclophosphonate may
improve the properties and biological activities of the compounds
synthesis of fluorine substituted cyclophosphonate analogs, which
encourage us to design a series of 2-phenoxyacetoxymethyl-1,3,2-
dioxaphosphinan-2-one derivatives. Based on the results of our
previous work [6–8], the 2-Cl-4-F, 2-F-4-Cl, 2-F, 4-F and 3-CF3
groups were introduced as X or Y. In this paper, fourteen novel 2-
(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-1,3,2-dioxapho-
sphinan-2-one containing fluorine 5a-n and three fluorine free
derivatives 5o-q were conveniently synthesized. The results of
bioassay showed that some of the target compounds display
promising herbicidal activity and are safe to some tested crops.
2. Results and discussions
2.1. Synthesis
According to the reported method [10], substituted phenox-
yacetic acids 1 were prepared starting from the substituted
phenols and ethyl bromoacetate in good yields. Treatment of the
1,3,2-dioxaphosphinane 3 [11] with aldehydes in the presence of
triethylamine readily led to the corresponding 1-hydroxycyclo-
phosphonates 4. The title compounds
5 were prepared by
condensation of the intermediates 4 with substituted phenox-
yacetyl chorides in chloroform at room temperature. The synthetic
pathway is outlined in Scheme 3 and the structures of title
compounds 5a–q are given in Table 1.
* Corresponding author. Tel.: +86 27 67867960; fax: +86 27 67867960.
E-mail addresses: he1208@mail.ccnu.edu.cn (H.-W. He),
penghao@mail.ccnu.edu.cn (H. Peng).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.06.020

W. Wang et al. / Journal of Fluorine Chemistry 142 (2012) 24–28
25
O
N
F
N
N
O
F3C
Cl
O
O
N
F
F3C
O
N
O
S
H
N
O
O
O
flumioxazin
flufenatet
haloxyfop
CF2H
N
O
F
F
O
S
O
N
N
N
CF3
H
N
CF3
N
N
N
N
N
Cl
SO2NHCNH
O
F
CO2Et
N
OCH3
Cl
flumetsulam
carfentrazone-ethyl
tritosulfuron
Scheme 1.
R1O
R2O
O
Structure-activity relationship analysis indicated that the struc-
ture and position of substituents X, Y in benzene ring had great
influence on the herbicidal activity. The compounds 5b, 5g and 5m
with 3-CF3 on the phenoxy-benzene ring showed better herbicidal
activities compared to the unsubstituted compounds 5o–5q that
are almost inactive. And the compounds 5e, 5j, 5l with 2-Cl-4-F
substitution as X and Y showed higher herbicidal activities even
than those of compounds 5b, 5g and 5m. However, the
introduction of 2-F-4-Cl as X and Y, resulted in the compound
5d, 5i and 5k, with some decrease in herbicidal activity. These
results indicated that fluorine moiety introduced to the core
cyclophosphonate structure was useful for the improvement of
herbicidal activity. Especially, the introducing of 2-Cl-4-F groups
made prominent enhancement on inhibitory activity.
As seen from Table 1, compounds 5a–q displayed much higher
herbicidal activity against dicotyledonous plants than monocoty-
ledons ones. Especially compounds with 2-Cl, 4-F as X and Y, such as
5e, 5j and 5l exhibited high and broad spectrum herbicidal activity
(ꢀ90% inhibition) at a dosage of 150 g ai/ha against dicotyledonous
weeds such as A. theophrasti, B. juncea, A. retroflexus and E. prostrate.
And the compounds with 3-CF3 on the phenoxy-benzene ring, such
X
P
O
O
R3
Y
O
I
Scheme 2.
2.2. Greenhouse herbicidal activity and crop selectivity
The herbicidal activities of compounds 5a–q were evaluated at
a dosage of 150 g ai/ha in greenhouse using the previously reported
procedure [6–8]. They were tested for post-emergence inhibitory
effect against seven weeds. Monocotyledonous weeds such as
Digitaria sanguinalis, Echinochloa crusgalli, Setaira viridis and
dicotyledonous weeds such as Abutilon theophrasti, Brassica juncea,
Amaranthus retroflexus and Eclipta prostrate.
Their herbicidal activities are summarized in Tables 1 and 2.
And the results of the crop selectivity are shown in Table 3.
X
X
EtO
O
Br
OH-
H+
K2CO3
Me2SO
HO
O
O
HO
+
Y
Y
1
X
SOCl2
Cl
O
Y
O
2
O
O
OH
OH
O
PH
O
O
RCHO
Et3N
EtOH
PCl3
P
OH
O
R
4
3
O
O
O
X
P
(C2H5)3N
O
O
+
4
2
Y
R
O
5
Scheme 3.

26
W. Wang et al. / Journal of Fluorine Chemistry 142 (2012) 24–28
Table 1
their structure-activity relationships were studied. All of these
compounds exhibited moderate to good herbicidal activities.
Especially, compound 5l showed good herbicidal activities even at
a dose of 75 g ai/ha. It was found that a suitable group at the 2,4-
positions of phenoxy-benzene ring was essential for high
herbicidal activity. Furthermore, compound 5l also showed good
selectivity between weeds and crops, which could be a lead
compound for further development. Our result showed fluorine or
trifluoromethyl group as X or Y on benzene ring had a very
important effect on herbicidal activity, however a satisfactory
herbicidal activity of title compound 5 required a reasonable
combination both type and position of fluorine – containing group
as X or Y on benzene ring.
Structures and herbicidal activity of compounds 5a–q (150 g ai/ha).
Compd
R
X
Y
Post-emergence activity (%)
aDS
EC
SV
AT
45
BJ
AR
40
EP
5a
5b
5c
5d
5e
5f
2-furyl
2-furyl
2-furyl
2-furyl
2-furyl
Ph
2-F
3-CF3
4-F
2-F
2-Cl
2-F
3-CF3
4-F
2-F
2-Cl
2-F
2-Cl
3-CF3
4-F
H
H
0
0
0
0
0
0
45
90
70
70
95
40
95
55
70
95
75
95
85
75
40
30
10
30
50
40
70
90
30
60
70
75
90
60
95
50
70
10
10
10
H
85
80
70
30
H
70
40
70
0
50
30
75
0
30
0
4-Cl
4-F
H
70
70
50
0
100
40
100
30
5g
5h
5i
Ph
H
0
0
0
100
40
70
Ph
H
0
0
0
70
Ph
4-Cl
4-F
4-Cl
4-F
H
40
30
0
40
70
0
40
60
0
75
80
5j
Ph
100
75
100
60
5k
5l
CH3
CH3
70
0
85
60
40
0
70
0
100
100
75
100
50
4. Experimental
5m
5n
5o
5p
5q
CH3
CH3
H
50
0
30
0
70
Mass spectra were measured on a Finnigan TraceMS 2000
spectrometer. Infrared spectra were recorded in potassium
bromide disks on a Nicolet Avatar360 FTIR spectrometer. 1H,
13C, 31P and 19F NMR spectra were recorded on a Varian Mercury-
Plus400 or 600 spectrometer with CDCl3 as the solvent and TMS as
the internal standard. Elemental analysis was performed by
Elementar Vario EL III elementary analyzer. Melting points (mp)
were measured on an electrothermal melting point apparatus and
temperature uncorrected. All of the solvents were anhydrous.
Phosphorous trichloride, triethyl amine and thionyl chloride were
distilled before the reaction. Samples were purified by flash
chromatography with silica gel.
2-furyl
Ph
H
10
30
H
H
0
0
0
10
30
CH3
H
H
0
0
0
10
10
a
DS for Digitaria sanguinalis; EC for Echinochloa crusgalli; SV for Setaira viridis; AT
for Abutilon theophrasti; BJ for Brassica juncea;AR for Amaranthus retroflexus; EP for
Eclipta prostrate.
Table 2
Further herbicidal testing of compounds 5g, 5l and 5m.
Compd
Dosage (g ai/ha)
Post-emergence activity (%)
aEC
SV
DS
AT
BJ
AR
EP
b
5g
5l
37.5
75
0
0
0
/
30
60
/
30
40
60
100
/
0
0
0
0
/
0
4.1. Synthesis of compounds 1 and 2
37.5
75
40
75
/
70
60
/
30
60
/
60
100
/
60
85
/
/
5m
37.5
75
/
The substituted phenoxyacetic acid 1 was synthesized by a
standard method [2]. The corresponding substituted phenoxya-
cetyl chloride 2 could be easily obtained as a yellow liquid in 90%
yield by treated compound 1 with thionyl chloride.
40
0
0
100
/
0
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.
b
Not test.
4.2. Synthesis of 1-hydroxylcyclophosphonate 4
Table 3
1-Hydroxycyclophosphonate
reaction of 1,3,2-dioxaphosphinane
4
could be prepared by the
and several kinds of
Crop Selectivity of Compound 5g and 5l post-emergence activity (%) 150 g ai/ha.
3
aldehydes using triethylamine as catalyst in yield of 65–94%
according to literatures [12,13].
Compd
Crops
Rice
Corn
Cotton
Soybean
Rape
Wheat
5g
5l
0
0
10
10
20
20
10
10
0
0
4.3. General synthesis of title compounds 5a–q
10
10
>10% not safe to crops; 0–10% be safe to crops.
A solution of substituted phenoxyacetyl chloride 2 (0.011 mol)
in chloroform (15 mL) was added to stirred mixture of 1-
as 5b, 5g and 5m, showed high herbicidal activities (>85%
inhibition) at a dosage of 150 g ai/ha against A. theophrasti and B.
juncea.
hydroxycyclophosphonate
4
(0.01 mol) and triethylamine
(0.011 mol) in chloroform (15 mL) at 2–4 8C. The resulting mixture
was stirred at ambient temperature for 2–3 h, then washed with
0.1 mol/L HCl, saturated NaHCO3 and brine separately, dried and
evaporated. The residue was chromatographed on silica gel using
acetone-petroleum ether (1:4) as the eluent to afford the
compounds 5a–q as a yellow oil or white solid.
In addition, compounds 5g, 5l and 5m were selected for further
herbicidal evaluation and the results are listed in Table 2, which
indicate that compound 5l exhibited high herbicidal activity (100%
inhibition) against A. theophrasti and B. juncea, and compound 5m
showed high herbicidal activity (100% inhibition) against A.
theophrasti at a dosage of 75 g ai/ha. Even at a dosage as low as
37.5 g ai/ha, compound 5l still exhibited broad herbicidal activity.
Furthermore, compounds 5g and 5l were selected to evaluate their
crop selectivity at a dosage of 150 g ai/ha. As shown in Table 3,
compounds 5g and 5l are safe to rice, corn, cotton, rape and wheat,
and compound 5g has no injury to rice, corn and wheat.
4.3.1. 2-[(2-Fluorophenoxy)acetoxy](furan-2-yl)methyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one (5a)
Yellow oil; yield 75%; n2D0 1.5051; IR (KBr):
n
3124, 2973, 1765,
1H NMR (400 MHz,
7.47–6.70 (m, 6H, –C6H4, 5 and 4-furanyl-H), 6.53–6.49
1506, 1288, 1173, 1062, 1012, 831 cmÀ1
CDCl3):
;
d
(d, J = 14.4 Hz, PCHO), 6.42 (s, 1H, 3-furanyl-H), 4.79 (s, 2H,
OCH2CO), 4.25–4.05 (m, 4H, 2 Â (OCH2)), 1.28 (s, 3H), 0.93 (s, 3H);
3. Conclusion
19F NMR (376 MHz, CDCl3): -134.56; 13C NMR (100 MHz, CDCl3):
d d
167.07, 152.47 (d, 1JC-F = 243.5 Hz), 149.67, 145.16, 144.11, 124.42,
122.82, 116.60 (d, J = 17.9 Hz), 115.74 (d, J = 19.5 Hz), 113.05,
A series of 2-(substituted phenoxyacetoxy)alkyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one derivatives were synthesized, and
1
111.04, 66.38, 64.07 (d, JC-P = 170.7 Hz), 32.39, 21.69, 20.43; 31P

W. Wang et al. / Journal of Fluorine Chemistry 142 (2012) 24–28
27
NMR (160 MHz, CDCl3):
d
5.85; EI-MS (70 eV): m/z 398 (M+); Anal.
4.3.6. 2-[(2-Fluorophenoxy)acetoxy](phenyl)methyl-5,5-dimethyl-
Calcd for C18H20FO7P: C, 54.28; H, 5.06; Found: C, 53.89; H, 4.73.
1,3,2-dioxaphosphinan-2-one (5f)
Yellow solid; yield 77%; mp 70–71 8C; IR (KBr):
1751, 1613, 1505, 1291, 1190, 1055, 1005, 836 cmÀ1
(400 MHz, CDCl3): 7.44–6.89 (m, 9H), 6.36 (d, 1H, J = 12.4 Hz,
n
3068, 2972,
;
4.3.2. 2-[(3-Trifluoromethylphenoxy)acetoxy](furan-2-yl)methyl-
1H NMR
5,5-dimethyl-1,3,2-dioxaphosphian-2-one (5b)
d
Yellow oil; yield 75%; n2D0 1.5612; IR (KBr):
n
2972, 1742, 1596,
1H NMR (400 MHz,
7.46 (s, 1H, 5-furanyl-H), 7.32–6.70 (m, 5H, –C6H4, 4-
PCHO), 4.83 (d, 2H, J = 3.6 Hz, OCH2CO), 4.16–4.04 (m, 4H,
1492, 1261, 1170, 1062, 1008, 827 cmÀ1
CDCl3):
;
2 Â (OCH2)), 1.18 (s, 3H), 0.91 (s, 3H); 19F NMR (376 MHz, CDCl3):
1
d
d
-134.72; 13C NMR (100 MHz, CDCl3):
d
166.75, 152.06 (d, JC-
furanyl-H), 6.53–6.49 (d, 1H, J = 13.2 Hz, PCHO), 6.42 (s, 1H, 3-
furanyl-H), 4.78 (s, 2H, OCH2CO), 4.20–4.01 (m, 4H, 2 Â (OCH2)),
F = 244.20 Hz), 145.09 (d, J = 10.30 Hz), 131.99, 128.81, 128.37,
127.44 (d, J = 5.30 Hz), 126.66, 122.41 (d, J = 6.50 Hz), 116.29 (d,
1
1.22 (s, 3H), 0.92 (s, 3H); 19F NMR (376 MHz, CDCl3):
d
-63.69; 13
C
J = 17.90 Hz), 115.12, 71.33 (d, JC-P = 164.60 Hz), 65.99, 32.08,
NMR (100 MHz, CDCl3):
d
166.92, 157.33, 144.93, 144.02, 131.70
21.29, 20.07; 31P NMR (160 MHz, CDCl3):
d 7.94; EI-MS (70 eV): m/
2
1
(q, JC-F = 30.76 Hz), 130.12, 123.49 (q, JC-F = 270.80 Hz), 118.50,
117.71, 111.45, 111.39, 110.94, 64.93, 63.42 (d, 1JC-P = 170.70 Hz),
32.23, 21.39, 20.33; 31P NMR (160 MHz, CDCl3):
z 408 (M+); Anal. Calcd for C20H22FO6P: C, 58.82; H, 5.43. Found: C,
58.81; H, 5.15.
d 5.94; EI-MS
(70 eV): m/z 448 (M+); Anal. Calcd for C19H20F3O7P: C, 50.90; H,
4.3.7. 2-[(3-Trifluoromethylphenoxy)acetoxy](phenyl)methyl-5,5-
4.50; Found: C, 50.68; H, 4.16.
dimethyl-1,3,2-dioxaphosphinan-2-one (5g)
White solid; yield 75%; mp 101–102 8C; IR (KBr):
1594, 1494, 1771, 1288, 1171, 1063, 1012, 836 cmÀ1; 1H NMR (400
MHz, CDCl3): 7.45–7.05 (m, 9H), 6.37 (d, 1H, J = 12.8 Hz, PCHO),
n 3066, 2972,
4.3.3. 2-[(4-Fluorophenoxy)acetoxy](furan-2-yl)methyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one (5c)
d
White solid; yield 76%; mp 67–70 8C; IR (KBr):
1770, 1506, 1290, 1173, 1061, 1012, 947,830, 761 cmÀ1
(400 MHz, CDCl3): 7.47 (s, 1H, 5-furanyl-H), 6.99–6.95 (m, 2H, 3
n
3077, 2972,
;
4.81 (d, 2H, J = 4.8 Hz, OCH2CO), 4.09–3.94 (m, 4H, 2 Â (OCH2)),
1H NMR
1.26 (s, 3H), 0.92 (s, 3H); 19F NMR (376 MHz, CDCl3):
NMR (100 MHz, CDCl3):
d
-63.69; 13
C
2
d
d
166.90, 157.41, 131.97, 131.60 (q, JC-
1
and 5-phenyl-H), 6.84–6.80 (m, 2H, 2 and 6-phenyl-H), 6.73–6.71
(m, 1H, 4-furanyl-H), 6.53–6.49 (d, 1H, J = 12.0 Hz, PCHO), 6.42–
6.41 (m, 1H, 3-furanyl-H), 4.69 (s, 1H, OCH2CO), 4.16–4.01 (m, 4H,
F = 32.33 Hz), 130.18, 129.13, 128.61, 127.75, 123.47 (q, JC-
F = 268.30 Hz), 118.53, 117.70, 111.57, 70.83 (d, 1JC-
P = 165.00 Hz), 65.09, 32.27, 21.37, 20.53; 31P NMR (160 MHz,
2 Â (OCH2)), 1.22 (s, 3H), 0.94 (s, 3H); 19F NMR (376 MHz, CDCl3):
CDCl3):
C21H22F3O6P: C, 55.03; H, 4.84. Found: C, 55.35; H, 4.55.
d
8.57; EI-MS (70 eV): m/z 458 (M+); Anal. Calcd for
1
d
-123.12; 13C NMR (100 MHz, CDCl3):
d
165.18, 157.15 (d, JC-
F = 236.30 Hz), 154.74, 146.16, 143.82, 115.70 (d, J = 22.90 Hz),
1
115.29 (d, J = 8.10 Hz), 112.04, 110.87, 65.78, 63.38 (d, JC-
4.3.8. 2-[(4-Fluorophenoxy)acetoxy](phenyl)methyl-5,5-dimethyl-
P = 172.30 Hz), 32.42, 21.65, 20.71; 31P NMR (160 MHz, CDCl3):
d
1,3,2-dioxaphosphinan-2-one (5h)
6.45; EI-MS (70 eV): m/z 398 (M+); Anal. Calcd for C18H20FO7P: C,
Yellow solid; yield 77%; mp 110–113 8C; IR (KBr):
1769, 1603, 1507, 1387, 1287, 1191, 1058, 997, 836 cmÀ1; 1H NMR
(400 MHz, CDCl3): 7.45–6.81 (m, 9H, –C6H5, –C6H3), 6.38–6.34 (d,
n 3073, 2969,
54.28; H, 5.06; found: C, 54.48; H, 5.39.
d
4.3.4. 2-[(4-Chloro-2-fluorophenoxy)acetoxy](furan-2-yl)methyl-
1H, J = 12.0 Hz, PCHO), 4.78–4.68 (dd, 2H, J = 16.8 Hz, J = 16.4 Hz,
OCH2CO), 4.11–3.93 (m, 4H, 2 Â (OCH2)), 1.15 (s, 3H), 0.91 (s, 3H);
5,5-dimethyl-1,3,2-dioxaphosphinan-2-one (5d)
White solid; yield 80%; mp 78–80 8C; IR (KBr):
1502, 1289, 1174, 1061, 1013, 947, 861, 799 cmÀ1
(400 MHz, CDCl3): 7.44 (s, 1H, 5-furanyl-H), 7.15–6.78 (m, 3H,
n
3070, 2979,
;
19F NMR (376 MHz, CDCl3):
d
-123.15; 13C NMR (100 MHz, CDCl3):
d
1H NMR
167.31, 157.66 (d, JC-F = 238.20 Hz), 153.45, 132.01, 129.07,
128.46 (d, J = 19.00 Hz), 127.76 (d, J = 6.10 Hz), 115.91 (d,
1
d
1
3,5,6-phenyl-H), 6.71 (s, 1H, 4-furanyl-H), 6.50–6.45 (d, 1H,
J = 14.0 Hz, PCHO), 6.41 (s, 1H, 3-furanyl-H), 4.78 (s, 1H, OCH2CO),
4.19–4.00 (m, 4H, 2 Â (OCH2)), 1.21 (s, 3H), 0.93 (s, 3H); 19F NMR
J = 23.30 Hz), 115.64 (d, J = 8.00 Hz), 70.80 (d, JC-P = 165.00 Hz),
65.51, 32.27, 21.41, 20.55; 31P NMR (160 MHz, CDCl3):
d 8.55; EI-
MS (70 eV): m/z 408 (M+); Anal. Calcd for C20H22FO6P: C, 58.82; H,
(376 MHz, CDCl3):
152.30 (d, JC-F = 248 Hz), 146.13, 145.54 (d, J = 10.30 Hz), 143.82,
125.40, 124.14, 116.87 (d, J = 21.70 Hz), 115.55, 112.02 (d,
d
-131.19; 13C NMR (100 MHz, CDCl3):
d
165.07,
5.43. Found: C, 59.01; H, 5.65.
1
4.3.9. 2-[(2-Fluoro-4-chlorophenoxy)acetoxy](phenyl)methyl-5,5-
1
J = 6.10 Hz), 110.87, 65.63, 63.30 (d, JC-P = 172.30 Hz), 32.12,
dimethyl-1,3,2-dioxaphosphinan-2-one (5i)
21.23, 20.41; 31P NMR (160 MHz, CDCl3):
d
6.11; EI-MS (70 eV):
Yellow solid; yield 75%; mp 117–119 8C; IR (KBr):
2895, 1753, 1604, 1494, 1275, 1188, 1057, 943, 745 cmÀ1; 1H NMR
(600 MHz, CDCl3): 7.43–6.82 (m, 8H, –C6H5, –C6H3), 6.36–6.33 (d,
n 3067, 2974,
m/z 432 (M+); Anal. Calcd for C18H19ClFO7P: C, 49.96; H, 4.43;
Found: C, 50.11; H, 4.49.
d
1H, J = 12.0 Hz, PCHO), 4.80 (s, 2H, OCH2CO), 4.10–3.96 (m, 4H,
4.3.5. 2-[(2-Chloro-4-fluorophenoxy)acetoxy](furan-2-yl)methyl-
2 Â (OCH2)), 1.16 (s, 3H), 0.90 (s, 3H); 19F NMR (376 MHz, CDCl3):
1
5,5-dimethyl-1,3,2-dioxaphosphinan-2-one (5e)
d
-131.03; 13C NMR (100 MHz, CDCl3):
d
166.33, 151.75 (d, JC-
White solid; yield 78%; mp 58–61 8C; IR (KBr):
1771, 1499, 1292, 1174, 1059, 947, 861, 801 cmÀ1
(400 MHz, CDCl3): 7.46 (s, 1H, 5-furanyl-H), 7.16–7.13 (dd, 1H,
n
3076, 2972,
;
F = 249.20 Hz), 143.90 (d, J = 9.90 Hz), 131.69, 128.80, 128.27,
127.42 (d, J = 5.30 Hz), 126.63 (d, J = 8.80 Hz), 124.01, 116.89 (d,
1H NMR
1
d
J = 21.70 Hz), 116.01, 70.85 (d, JC-P = 164.60 Hz), 66.05, 31.97,
J = 3.2 Hz, J = 3.2 Hz, 3-phenyl-H), 6.92–6.87 (m, 1H, 5-phenyl-H),
6.83–6.79 (dd, 1H, J = 4.8 Hz, J = 4.8 Hz, 6-phenyl-H), 6.71 (s, 1H, 4-
furanyl-H), 6.52-6.48 (d, 1H, J = 14.0 Hz, PCHO), 6.42 (s, 1H, 3-
furanyl-H), 4.76 (s, 1H, OCH2CO), 4.18–4.02 (m, 4H, 2 Â (OCH2)),
21.14, 20.13; 31P NMR (160 MHz, CDCl3):
d 8.25; EI-MS (70 eV): m/
z 442 (M+); Anal. Calcd for C20H21ClFO6P: C, 54.25; H, 4.78; Found:
C, 54.55; H, 4.98.
1.22 (s, 3H), 0.93 (s, 3H); 19F NMR (376 MHz, CDCl3):
d
-120.30; 13
C
4.3.10. 2-[(2-Chloro-4-fluorophenoxy)acetoxy](phenyl)methyl-5,5-
1
NMR (100 MHz, CDCl3):
d
165.13, 156.38 (d, JC-F = 240.10 Hz),
dimethyl-1,3,2-dioxaphosphinan-2-one (5j)
150.70, 146.09, 143.80, 117.53, 117.27, 114.17 (d, J = 8.80 Hz),
113.88 (d, J = 22.10 Hz), 111.99 (d, J = 6.10 Hz), 110.83, 65.61, 63.29
Yellow solid; yield 77%; mp 110–112 8C; IR (KBr):
1753, 1623, 1500, 1281, 1189, 1048, 995, 839 cmÀ1
(400 MHz, CDCl3): 7.45–6.81 (m, 8H, Phenyl-H), 6.38–6.34 (d, 1H,
J = 12.4 Hz, PCHO), 4.80 (s, 2H, OCH2CO), 4.11–3.92 (m, 4H,
2 Â (OCH2)), 1.16 (s, 3H), 0.90 (s, 3H); 19F NMR (376 MHz, CDCl3):
n
3078, 2971,
;
1H NMR
1
(d, JC-P = 172.30 Hz), 32.11, 21.22, 20.40; 31P NMR (160 MHz,
d
CDCl3):
d
6.24; EI-MS (70 eV): m/z 432 (M+); Anal. Calcd for
C18H19ClFO7P: C, 49.96; H, 4.43; Found: C, 50.05; H, 4.59.

28
W. Wang et al. / Journal of Fluorine Chemistry 142 (2012) 24–28
1
d
-120.36; 13C NMR (100 MHz, CDCl3):
d
166.46, 156.79 (d, JC-
4.3.15. 2-phenoxyacetoxy(furan-2-yl)methyl-5,5-dimethyl-1,3,2-
F = 242.30 Hz), 149.30, 131.74, 128.66, 128.43, 127.75, 123.42,
dioxaphosphinan-2-one (5o)
117.38, 114.72 (d, J = 8.30 Hz), 113.79, 70.75 (d, 1JC-P = 164.60 Hz),
yellow oil; yield, 78%; n2D0 1.5169; IR (KBr, cmÀ1):
n 3060, 2970,
66.31, 31.98, 21.13, 20.22; 31P NMR (160 MHz, CDCl3):
d
8.48; EI-
1744, 1600, 1494, 1264, 1174, 1060, 1009, 833. 1H NMR (400 MHz,
CDCl3): d 7.48–6.72 (m, 7H, –C6H5, 5 and 4-furanyl-H), 6.55–6.51
MS (70 eV): m/z 442 (M+); Anal. Calcd for C20H21ClFO6P: C, 54.25;
H, 4.78; Found: C, 54.55; H, 4.98.
(d, J = 14.4 Hz, PCHO), 6.42 (s, 1H, 3-furanyl-H), 4.74 (s, 2 H,
OCH2CO), 4.19–4.04 (m, 4H, 2 Â (OCH2)), 1.24 (s, 3H), 0.93 (s, 3H).
4.3.11. 2-[(4-Chloro-2-fluorophenoxy)acetoxy](methyl)methyl-5,5-
13C NMR (100 MHz, CDCl3):
d 167.42, 157.23, 145.22, 143.94,
1
dimethyl-1,3,2-dioxaphosphinan-2-one (5k)
129.47, 121.81, 114.35, 112.76, 110.93, 64.96, 63.72 (d, JC-
White solid; yield 80%; mp 107–109 8C; IR (KBr):
1775, 1494, 1287,1246, 1194, 1085, 1047, 1004, 975, 841,
798 cmÀ1 1H NMR (600 MHz, CDCl3):
7.15–6.82 (m, 3H, 3, 5
n
3079, 2974,
P = 169.90 Hz), 32.28, 21.51, 20.34; 31P NMR (160 MHz, CDCl3):
d
5.72; EI-MS m/z (%): 380 (M+, 7); Anal.Calcd for C18H21O7P: C,
;
d
56.84; H, 5.57. Found: C, 56.70; H, 5.18.
and 6-phenyl-H), 5.50–5.46 (q, 1H, J = 7.0 Hz, PCHO), 4.78–4.68 (s,
2H, OCH2CO), 4.14–3.99 (m, 4H, 2 Â (OCH2)), 1.60–1.55 (dd, 3H,
J = 7.2 Hz, J = 7.2 Hz, PCH(CH3)O), 1.17 (s, 3H), 0.99 (s, 3H); 19F
4.3.16. 2-phenoxyacetoxy(phenyl)methyl-5,5-dimethyl-1,3,2-
dioxaphosphinan-2-one (5p)
NMR (376 MHz, CDCl3):
d
-131.29; 13C NMR (100 MHz, CDCl3):
d
yellow solid; yield, 80%; mp, 80–81 8C; IR (KBr, cmÀ1):
n
3064,
2971, 1765, 1598, 1492, 1290, 1194, 1054, 1004, 830. 1H NMR (400
MHz, CDCl3): 7.44–6.87 (m, 10H, –C6H5, –C6H5), 6.38–6.34 (d, 1H,
1
167.22, 152.87 (d, JC-F = 248.40 Hz), 144.47 (d, J = 10.10 Hz),
125.61, 124.37 (d, J = 3.40 Hz), 117.73 (d, J = 21.7 Hz), 115.74,
d
1
66.59, 65.15 (d, JC-P = 165.80 Hz), 32.33, 21.30, 20.61 14.57; 31P
J = 12.0 Hz, PCHO), 4.77–4.76 (d, 2H, J = 3.6 Hz, OCH2CO), 4.13–3.98
(m, 4H, 2 Â (OCH2)), 1.17 (s, 3H), 0.91 (s, 3H). 13C NMR (100 MHz,
NMR (160 MHz, CDCl3):
d
12.36; EI-MS (70 eV): m/z 380 (M+);
Anal. Calcd for C15H19ClFO6P: C, 47.32; H, 5.03; Found: C, 47.65; H,
5.23.
CDCl3): d 167.58, 157.35, 132.32, 129.68, 129.10, 128.65, 127.83,
1
121.97, 114.42, 71.27 (d, JC-P = 163.80 Hz), 65.13, 32.34, 21.61,
20.56; 31P NMR (160 MHz, CDCl3): 7.97; EI-MS m/z (%): 390 (M+,
d
4.3.12. 2-[(2-Chloro-4-fluorophenoxy)acetoxy](methyl)methyl-5,5-
1); Anal. Calcd for C20H23O6P: C, 61.54; H, 5.94. Found: C, 61.25; H,
5.68.
dimethyl-1,3,2-dioxaphosphinan-2-one (5l)
White solid; yield 78%; mp 82–84 8C; IR (KBr):
1738, 1496, 1247, 1195, 1070, 1001, 965, 829, 800 cmÀ1; 1H NMR
(600 MHz, CDCl3): 7.17–7.15 (dd, 1H, J = 2.4 Hz, J = 2.4 Hz, 3-
n 3062, 2967,
4.3.17. 2-phenoxyacetoxy(methyl)methyl-5,5-dimethyl-1,3,2-
d
dioxaphosphinan-2-one (5q)
phenyl-H), 6.96-6.84 (m, 2H, 5 and 6-phenyl-H), 5.53–5.47 (m, 1H,
PCHO), 4.77–4.70 (dd, 2H, J = 16.8 Hz, J = 16.2 Hz, OCH2CO), 4.13–
3.97 (m, 4H, 2 Â (OCH2)), 1.60–1.56 (dd, 3H, J = 7.2 Hz, J = 6.6 Hz,
white oil; yield, 81%; n2D0 1.3690; IR (KBr, cmÀ1):
n
3091, 2967,
1764, 1483, 1237, 1197, 1053, 1000, 844, 805. 1H NMR (600 MHz,
CDCl3): 7.32–6.88 (m, 5H, –C6H5), 5.53–5.47 (m, 1H, PCHO), 4.71
d
PCH(CH3)O), 1.16 (s, 3H), 0.99 (s, 3H); 19F NMR (376 MHz, CDCl3):
(s, 2H, OCH2CO), 4.12–3.98 (m, 4H, 2 Â (OCH2)), 1.60–1.55 (dd, 3H,
1
d
-120.23; 13C NMR (100 MHz, CDCl3):
d
167.02, 157.04 (d, JC-
J = 7.2 Hz, J = 7.2 Hz, PCH(CH3)O), 1.17 (s, 3H), 0.97 (s, 3H); 13C
F = 240.80 Hz), 149.57, 123.70, 117.67 (d, J = 25.9 Hz), 114.98 (d,
NMR (100 MHz, CDCl3):
d
167.30, 156.89, 129.09, 121.43, 113.91,
64.87 (d, JC-P = 146.00 Hz), 64.73, 31.90, 20.04, 20.21, 14.25; 31P
NMR (160 MHz, CDCl3):
12.26; EI-MS m/z (%): 328 (M+, 5); Anal.
1
1
J = 9.10 Hz), 114.08 (d, J = 22.9 Hz), 66.60, 65.15 (d, JC-
P = 166.10 Hz), 32.34, 21.31, 20.64 14.59; 31P NMR (160 MHz,
d
CDCl3):
d
12.22; EI-MS (70 eV): m/z 380 (M+); Anal. Calcd for
Calcd for C15H21O6P: C, 54.88; H, 6.45. Found: C, 55.23; H, 6.81.
C
15H19ClFO6P: C, 47.32; H, 5.03; Found: C, 47.41; H, 5.30.
Acknowledgements
4.3.13. 2-[(3-Trifluoromethylphenoxy)acetoxy](methyl)methyl-5,5-
dimethyl-1,3,2-dioxaphosphinan-2-one (5m)
We gratefully acknowledge financial support of this work 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).
White solid; yield 76%; mp 69–71 8C; IR (KBr):
1767,1594, 1494, 1331, 1171, 1065, 1012, 947, 877, 800 cmÀ1; 1H
NMR (400 MHz, CDCl3): 7.45–7.06 (m, 4H, –C6H4), 5.55–5.47 (m,
n 3094, 2974,
d
1H, PCHO), 4.75 (s, 2H, OCH2CO), 4.16–3.95 (m, 4H, 2 Â (OCH2)),
1.61–1.55 (dd, 3H, J = 7.2 Hz, J = 7.2 Hz, PCH(CH3)O), 1.15 (s, 3H),
1.02 (s, 3H); 19F NMR (376 MHz, CDCl3):
d
-63.72; 13C NMR
2
(100 MHz, CDCl3):
d
166.51, 158.63, 131.43 (q, JC-F = 32.00 Hz),
References
129.79, 123.73 (q, 1JC-F = 270.50 Hz), 117.66, 117.14, 110.91, 65.32,
1
64.35 (d, JC-P = 145.98 Hz), 31.51, 20.53, 19.78, 14.09; 31P NMR
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291–295.
(160 MHz, CDCl3):
d
12.50; EI-MS (70 eV): m/z 396 (M+); Anal.
Calcd for C16H20F3O6P: C, 48.49; H, 5.09; Found: C, 48.71; H, 5.38.
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(2005) 297–300.
4.3.14. 2-[(4-Fluorophenoxy)acetoxy](methyl)methyl-5,5-dimethyl-
1,3,2-dioxaphosphinan-2-one (5n)
White solid; yield 75%; mp 67–69 8C; IR (KBr):
1768, 1508, 1272, 1207, 1065, 1006, 952, 833, 799 cmÀ1; 1H NMR
(600 MHz, CDCl3): 7.01–6.83 (m, 4H, –C6H4), 5.53–5.49 (m, 1H,
n 3117, 2972,
[5] X.M. Zheng, Z. Li, Y.L. Wang, W.D. Chen, Q.C. Huang, C.X. Liu, G.H. Song, Journal of
Fluorine Chemistry 123 (2003) 163–169.
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[11] H. McCombie, B.C. Saunders, G.J. Stacey, Journal of the Chemical Society (1945)
380–382.
d
PCHO), 4.67 (s, 2H, OCH2CO), 4.11–4.00 (m, 4H, 2 Â (OCH2)), 1.60–
1.56 (q, 3H, J = 7.8 Hz, PCH(CH3)O), 1.16 (s, 3H), 1.00 (s, 3H); 19F
NMR (376 MHz, CDCl3): d d
-120.09; 13C NMR (100 MHz, CDCl3):
1
167.31, 157.30 (d, JC-F = 238.20), 153.21, 115.59 (d, J = 23.20 Hz),
1
115.38 (d, J = 8.00 Hz), 65.61, 64.69 (d, JC-P = 146.30 Hz), 31.99,
21.01, 20.27, 14.29; 31P NMR (160 MHz, CDCl3):
d 12.42; EI-MS
(70 eV): m/z 346 (M+); Anal. Calcd for C15H20FO6P: C, 52.03; H,
[12] F. Texier-Boullet, M. Lequitte, Tetrahedron Letters 27 (1986) 3515–3516.
[13] F. Texier-Boullet, A. Foucaud, Synthesis (1982) 916.
5.82; Found: C, 52.43; H, 5.95.