Synthesis and herbicidal activity of novel pyrimidinyl derivatives containing an α-amino phosphonate moiety

Article abstract of DOI:10.1080/10426501003598663

In order to find novel pyrimidinyl carboxylic acid analogs with high activity and low toxicity, a series of novel pyrimidinyl derivatives containing an -amino phosphonate moiety 5 was synthesized by the condensation of 4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxyacetic 3a or propionic acids 3b with dialkyl -amino substitutedbenzyl phosphonates 4. Their structures were characterized by spectroscopic data (IR, ¹H NMR, ³¹P NMR, MS) and elemental analyses. The results of preliminary herbicidal activities (in vitro) showed that most of these compounds exhibited higher herbicidal activities against dicotyledonous weeds (Brassica campestris L) than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays (in vivo) indicated that some of compounds 5 possessed selective herbicidal activity against amaranth pigweed (A. retroflexus) in post-emergence treatment. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426501003598663

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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Synthesis and Herbicidal Activity of
Novel Pyrimidinyl Derivatives Containing
an α-Amino Phosphonate Moiety
Zhi-Hua Yu a & De-Qing Shi a
a Key Laboratory of Pesticide and Chemical Biology , Ministry of
Education, College of Chemistry, Central China Normal University ,
Wuhan , Hubei , People's Republic of China
Published online: 05 Nov 2010.
To cite this article: Zhi-Hua Yu & De-Qing Shi (2010) Synthesis and Herbicidal Activity of Novel
Pyrimidinyl Derivatives Containing an α-Amino Phosphonate Moiety, Phosphorus, Sulfur, and Silicon
and the Related Elements, 185:11, 2316-2323, DOI: 10.1080/10426501003598663
To link to this article: http://dx.doi.org/10.1080/10426501003598663
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Phosphorus, Sulfur, and Silicon, 185:2316–2323, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003598663
SYNTHESIS AND HERBICIDAL ACTIVITY OF NOVEL
PYRIMIDINYL DERIVATIVES CONTAINING AN α-AMINO
PHOSPHONATE MOIETY
Zhi-Hua Yu and De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education,
College of Chemistry, Central China Normal University, Wuhan, Hubei,
People’s Republic of China
In order to find novel pyrimidinyl carboxylic acid analogs with high activity and low toxicity,
a series of novel pyrimidinyl derivatives containing an α-amino phosphonate moiety 5 was
synthesized by the condensation of 4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxyacetic 3a or
propionic acids 3b with dialkyl α-amino substitutedbenzyl phosphonates 4. Their structures
were characterized by spectroscopic data (IR, 1H NMR, 31P NMR, MS) and elemental
analyses. The results of preliminary herbicidal activities (in vitro) showed that most of these
compounds exhibited higher herbicidal activities against dicotyledonous weeds (Brassica
campestris L) than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays
(in vivo) indicated that some of compounds 5 possessed selective herbicidal activity against
amaranth pigweed (A. retroflexus) in post-emergence treatment.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords α-Amino phosphonate; aryloxyphenoxy carboxylic acid; herbicidal activity; pyrim-
idinylcarboxylic acid
INTRODUCTION
Since the late 1990s, pyrimidinyl carboxylic acid derivatives have been found to
be effective herbicides against barnyard grass in different growth stages including pre-
emergence treatment and excellent safety on transplanted rice crops, animals, fish, etc.
These herbicides, known as inhibitors of branched chain amino acids (ALS or AHAS)
synthase, have attracted considerable attention from pesticide scientists.1–5 To date, several
pyrimidyl carboxylic acid derivatives, such as bispyribac-sodium and pyriminobac-methyl,
have been used as commercial herbicides (Figure 1). Aryloxyphenoxypropionate (APP)
derivatives have been found to be the inhibitor of acetyl-coacarboxylase (ACCase) and they
have acted as an important class of herbicides in plant protection.6,7
Received 24 November 2009; accepted 6 January 2010.
This work was supported by the National Natural Science Foundation of China (20872046) and the Natural
Science Foundation of Hubei Province (2008CDB086).
Address correspondence to De-Qing Shi, Key Laboratory of Pesticide and Chemical Biology, Ministry of
Education, College of Chemistry, Central China Normal University, Wuhan 430079, Hubei, People’s Republic of
China. E-mail: chshidq@yahoo.com.cn
2316

NOVEL PYRIMIDINYL DERIVATIVES
2317
H CO
3
OCH
3
H C
NOCH
3
3
N
N
H CO
3
OCH
COOCH
N
3
3
O
COONa
O
N
N
N
N
OCH
3
H
N
O
O
H CO
3
N
OCH
3
CO Pr-n
2
OCH
3
Pyriminobac-methyl
Bispyribac-sodium
ZJ 0273
Figure 1 Structures of some commercial pyrimidinyl carboxylic acid and pyrimidinyl benzylamine herbicides.
When heterocyclic units were introduced to the APP skeleton, some efficient herbi-
cides were developed. Recently, α-amino phosphonic acid and their ester derivatives, as
bioisosteres of natural amino acids, have been receiving an increasing amount of attention
in medicinal chemistry and pesticide science due to their wide biological activities such as
enzyme inhibition, antibiotics, and haptens of catalytic antibodies, fungicides, herbicides,
plant regulators, and plant virucides.8–14 In order to find potent and selective herbicide
lead structures, we have synthesized a series of novel pyrimidinyl derivatives bearing an
α-amino phosphonate moiety 5 (Scheme 1), which are similar to APP inhibitor in some
extents, and compounds 5 were evaluated for herbicidal activities in this study.
H3CO
H3CO
K2CO3/THF
N
N
N
N
HO
O
OC2H5
O
O
O
R
OC2H5
O
SO2CH3
+
R
H3CO
H3CO
2
1
O
OR'
P
Ar
OR'
H3CO
H3CO
O
P
OR'
OR'
4
N
N
N
NaOH/HCl
NH2
O
O
R
OH
O
O
O
R
HN
N
Ar
DCC/CH2Cl2
H3CO
H3CO
O
5
3
R = H, CH3; R' = CH3, C2H5; n-Bu;
Ar = Ph, 2-ClC6H4, 4-FC6H4, 4-ClC6H4, 4-BrC6H4,
4-CH3C6H4, 4-CH3OC6H4, 2,4-Cl2C6H3
Scheme 1 Synthetic route to title compounds 5.
RESULTS AND DISCUSSION
Synthesis
4-(4,6-Dimethoxypyrimidin-2-yloxy)phenoxyacetic or propionic acids (3a, 3b)
were prepared by the reaction of 2-(4-hydroxyphenoxy)-carboxylates with (4,6-
dimethoxypyrimidin-2-yl)methylsulfone in potassium carbonate and refluxing THF, fol-
lowed by saponification. Finally, 2-[4-(4,6-dimethoxypyrimidin-2-yloxy)phenoxy]acetic
or propionic acid 3 reacted with α-amino phosphonates 4 using DCC as the dehydration
reagent to obtain the target compounds 5 in good yields. The structures of target compounds
1
5 were confirmed from their spectroscopic data (IR, H NMR, 31P NMR, EI-MS, or
ESI-MS) and elemental analyses.

2318
Z.-H. YU AND D.-Q. SHI
Herbicidal Activities
The preliminary herbicidal activity (in vitro) of the title compounds 5 against Brassica
campestris L. (rape) and Echinochloa crus-galli (barnyard grass) has been investigated at
the dosages of 100 mg/L and 10 mg/L, compared with the commercially available herbicide,
bispyribac-sodium, and is listed in Table S1 (Supplemental Materials, available online).
CONCLUSIONS
In summary, we have synthesized a series of novel pyrimidinyl derivatives containing
an α-amino phosphonate moiety 5. Their structures were clearly confirmed by spectroscopic
1
data (IR, H NMR, 31P NMR, MS) and elemental analyses. The results of preliminary
herbicidal activity of compounds 5 showed that some of the target compounds displayed
good herbicidal activity against the root of Brassica campestris L at the concentration of
100 mg/L. Further bioassays (in vivo) indicated some of compounds 5 showed selective
herbicidal activity against amaranth pigweed (A. retroflexus) in post-emergence treatments.
EXPERIMENTAL
Instruments
1H and 31P NMR spectra were performed on a Varian Mercury Plus-400 (400 MHz) or
Varian Mercury Plus-600 (600 MHz) spectrometer at room temperature in CDCl3 with TMS
and 85% H3PO4 as the internal and external standards, respectively; chemical shift values
(δ) were given in ppm. Elemental analyses were taken on a Germany Elementar Vario EL III
elemental analyses instrument. Mass spectra were measured on a Finnigan TraceMS 2000
spectrometer at 70 eV using EI method or Applied Biosystems API 2000 LC/MS/MS (ESI-
MS) spectrometer. The IR spectra were recorded on a Nicolet NEXUS470 spectrometer
as KBr pellets with absorption given in cm−1. The melting points were determined on an
X-4 binocular microscope melting point apparatus (Beijing Tech. Instruments Co., Beijing,
China) and were uncorrected. Analytical TLC was performed on silica gel GF254. Column
chromatographic purification was carried out using silica gel. Yields were not optimized.
Unless otherwise noted, all materials were commercially available and were used directly
without further purification. All solvents were dried and redistilled before use. Ethyl 2-
(4-hydroxyphenoxy)-acetate or -propionate were prepared from hydroquinone and ethyl
2-chloroacetate or 2-bromopropionate in sodium ethoxide ethanol solution according to the
reported methods.15 For acetate, yield 66%, mp 124.3–125.8◦C; and for propionate, yield
58%, mp 120.5–121.9◦C. Dialkyl α-amino phosphonates 4 were synthesized from aromatic
aldehyde, ammonium hydroxide, and dialkyl phosphites in moderate yields according to
the reported synthetic protocols.16,17
Synthesis of 4-(4,6-Dimethoxypyrimidin-2-yloxy)phenoxyacetic
or -propionic Acids (3a, 3b)
Ethyl 2-(4-hydroxyphenoxy)-propionate (2.10 g, 10 mmol), 4,6-dimethoxypyrimidin-
2-yl-methylsulfone (2.18 g, 10 mmol), and anhydrous potassium carbonate (2.07 g,
15 mmol) in dry THF (30 mL) were stirred under reflux for 5 h (monitored by TLC).
The solid was filtered off, and the liquid was poured into ice water (50 mL). The
crude product was collected by filtration. After recrystallization from ethyl acetate, ethyl
4-(4,6-dimethoxypyrimidin-2-yloxy)propionate was obtained as a light yellow crystals

NOVEL PYRIMIDINYL DERIVATIVES
2319
(2.68 g), yield: 77%, mp: 83.2–84.4◦C, which can be used for the next step without further
purification.
Ethyl 4-(4,6-dimethoxypyrimidin-2-yloxy)propionate (3.48 g, 10 mmol), sodium hy-
droxide (0.64 g, 16 mmol), water (10 mL), and ethanol (10 mL) were stirred at 80–90◦C for
1–2 h (monitored by TLC). The solution was acidified by dilute hydrochloride. The crude
product was collected by filtration, washed by ethyl ether, and 3b was obtained as a yellow
solid, yield: 92%, mp: 153.2–154.6◦C. 1H NMR (CDCl3, 600 MHz): δ 1.67 (d, J = 7.2 Hz,
3H, CH3), 3.82 (s, 6H, 2OCH3), 4.77 (q, J = 7.2 Hz, 1H, CH), 5.76 (s, 1H, pyrimidine-H),
6.90 (d, J = 8.4 Hz, 2H, ArH), 7.10 (d, J = 9.0 Hz, 2H, ArH), 13.06 (s, 1H, OH). Anal.
Calcd for C15H16N2O6: C, 56.25; H, 5.04; N, 8.75. Found: C, 56.06; H, 4.84; N, 8.93.
3a was prepared in a similar procedure, yield, 86%; yellow solid, mp 136.5–137.4◦C.
1H NMR (CDCl3, 400 MHz): δ 3.84 (s, 6H, 2OCH3), 4.51 (s, 2H, CH2), 5.79 (s, 1H,
pyrimidine-H), 6.94 (d, J = 8.2 Hz, 2H, ArH), 7.06 (d, J = 8.8 Hz, 2H, ArH), 12.95 (s, 1H,
OH). Anal. Calcd for C14H14N2O6: C, 54.90; H, 4.61; N, 9.15. Found: C, 55.13; H, 4.79;
N, 9.44.
General Synthetic Procedures for O,Oꢀ-Dialkyl
{2-[4-(4,6-Dimethoxypyrimidin-2-yloxy)phenoxy]acetamido
or -propionamido}substitutedphenyl Methylphosphonates 5
To
a
solution of α-aminophosphonate
4
(2.0 mmol) and 2-[4-(4,6-
dimethoxypyrimidin-2-yloxy)phenoxy]acetic or propionic acid 3 (2.0 mmol) in anhydrous
methylene chloride (10 mL), dicyclohexylcarbodiimide (DCC, 0.45 g, 2.2 mmol) in
anhydrous methylene chloride (3 mL) was added dropwise at 0–5◦C under stirring for
0.5 h. The mixture was allowed to be stirred at room temperature for 10–24 h (monitored
by TLC). The solid was filtered off, the solvent was removed, acetone (5 mL) was added
to the crude product, and the solid formed was filtered off again. After the removal of
the solvent followed by column chromatography of the crude product on silica gel using
a mixture of petroleum ether and acetone (v/v, 2:1) as the eluent, compounds 5 were
obtained as white solids or yellow liquids in 61–86% yields.
Data for 5a (Ar = 4-CH3C6H4, R = CH3, Rꢁ = C2H5): yield, 79%; white solid; mp
130.4–131.9◦C; IR (KBr): ν 3423 (N H), 3226 (C-H), 1693 (C O), 1403, 1210 (P O),
1
1029 (P O C), 982 (P C) cm−1; H NMR (CDCl3, 400 MHz): δ 1.14 (t, J = 7.2 Hz,
3H, CH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.62 (d, J = 6.8 Hz, 3H, CH3), 2.28 (s, 3H,
CH3), 3.84 (s, 6H, 2 CH3O), 3.86–4.14 (m, 4H, 2CH2), 4.68 (q, J = 6.8 Hz, 1H, CH),
5.45 (dd, J = 10.0 Hz, J = 20.8 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.86–7.12 (m,
8H, ArH), 7.30 (d, J = 8.8 Hz, 1H, NH); 31P NMR (CDCl3, 162 MHz): δ 18.65; EI-MS
(70ev): m/z 559.5 (M+, 15.8), 422 (37.5), 396.5 (80.3), 259 (96.4), 256 (31.1), 141 (77.7),
139 (100), 120 (28.7), 112 (81.8), 91(29.3), 80.5 (15.8), 77.5 (4.8), 70 (28.4). Anal. Calcd
for C27H34N3O8P: C, 57.96; H, 6.12; N, 7.51. Found: C, 58.04; H, 6.03; N, 7.76.
Data for 5b (Ar = Ph, R = CH3, Rꢁ = C2H5): yield, 84%; white solid; mp
1
147.7–148.5◦C; H NMR (CDCl3, 600 MHz): δ 1.13 (t, J = 7.2 Hz, 3H, CH3), 1.31
(t, J = 7.2 Hz, 3H, CH3), 1.63 (d, J = 7.2 Hz, 3H, CH3), 3.83 (s, 6H, 2CH3O), 3.74–4.14
(m, 4H, 2CH2), 4.68 (q, J = 6.6 Hz, 1H, CH), 5.48 (dd, J = 10.2 Hz, J = 20.7 Hz, 1H,
PCH), 5.78 (s, 1H, pyrimidine-H), 6.86–7.32 (m, 9H, ArH), 7.32 (s, 1H, NH); 31P NMR
(CDCl3, 243 MHz): δ 19.53; ESI-MS: m/z 583 (M++K-1, 8), 559 (18), 545.0 (M+, 100).
Anal. Calcd for C26H32N3O8P: C, 57.24; H, 5.91; N, 7.70. Found: C, 57.01; H, 5.77; N,
7.95.

2320
Z.-H. YU AND D.-Q. SHI
Data for 5c (Ar = 4-CH3O C6H4, R = CH3, Rꢁ = C2H5): yield, 82%; white solid;
mp 147.0–147.9◦C; 1H NMR (CDCl3, 600 MHz): δ 1.14 (t, J = 7.2 Hz, 3H, CH3), 1.31 (t,
J = 7.2 Hz, 3H, CH3), 1.62 (d, J = 7.2 Hz, 3H, CH3), 3.75 (s, 3H, OCH3), 3.81 (s, 6H,
2CH3O), 3.84–4.12 (m, 4H, 2CH2), 4.67 (q, J = 7.2 Hz, 1H, CH), 5.40 (dd, J = 10.2 Hz,
J = 20.7 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.76 (d, J = 8.4 Hz, 2H, ArH), 6.86
(d, J = 8.4 Hz, 2H, ArH), 7.09–7.14 (m, 4H, ArH), 7.29 (s, 1H, NH); 31P NMR (CDCl3,
243 MHz): δ 19.26; ESI-MS: m/z 612.5 (M++K-1, 12), 597.5 (M++Na-1, 38), 575.5 (M+,
100). Anal. Calcd for C27H34N3O9P: C, 56.34; H, 5.95; N, 7.30. Found: C, 56.48; H, 6.13;
N, 7.17.
Data for 5d (Ar = 2-ClC6H4, R = CH3, Rꢁ = C2H5): yield, 70%; white solid; mp
53.2–54.7◦C; 1H NMR (CDCl3, 600 MHz): δ 1.17 (t, J = 7.2 Hz, 3H, CH3), 1.36 (t, J =
7.2 Hz, 3H, CH3), 1.63 (d, J = 7.2 Hz, 3H, CH3), 3.68–4.20 (m, 4H, 2CH2), 3.83 (s, 6H,
2CH3O), 4.66 (q, J = 7.2 Hz, 1H, CH), 5.78 (s, 1H, pyrimidine-H), 5.99 (dd, J = 9.6 Hz,
J = 21.0 Hz, 1H, PCH), 6.85–7.43 (m, 8H, ArH), 7.48 (s, 1, NH); 31P NMR (CDCl3, 243
MHz): δ 18.91; ESI-MS: m/z 579.5 (M+, 100). Anal. Calcd for C26H31ClN3O8P: C, 53.84;
H, 5.39; N, 7.25. Found: C, 54.03; H, 5.50; N, 7.49.
Data for 5e (Ar = 4-CH3C6H4, R = CH3, Rꢁ = CH3): yield, 74%; white solid; mp
81.3–82.5◦C; 1H NMR (CDCl3, 400 MHz): δ 1.63 (d, J = 7.2 Hz, 3H, CH3), 2.35 (s, 3H,
CH3), 3.48 (d, J = 10.0 Hz, 3H, OCH3), 3.78 (d, J = 10.8 Hz, 3H, OCH3), 3.83 (s, 6H,
2CH3O), 4.68 (q, J = 7.2 Hz, 1H, CH), 5.50 (dd, J = 10.0 Hz, J = 20.8 Hz, 1H, PCH), 5.78
(s, 1H, pyrimidine-H), 6.86–7.32 (m, 8H, ArH); 31P NMR (CDCl3, 162 MHz): δ 22.19;
ESI-MS: m/z 569 (M++K-1, 27), 553 (M++Na-1, 64), 531 (M+, 100). Anal. Calcd for
C25H30N3O8P: C, 56.49; H, 5.69; N, 7.91. Found: C, 56.71; H, 5.55; N, 7.62.
Data for 5f (Ar = 2,4-Cl2C6H3, R = CH3, Rꢁ = C2H5): yield, 69%; white solid;
1
mp 82.7–84.3◦C; H NMR (CDCl3, 400 MHz): δ 1.26 (t, J = 7.2 Hz, 3H, CH3), 1.51
(t, J = 7.2 Hz, 3H, CH3), 1.63 (d, J = 7.2 Hz, 3H, CH3), 3.66–4.19 (m, 4H, 2CH2),
3.84 (s, 6H, 2CH3O), 4.67 (q, J = 7.2 Hz, 1H, CH), 5.79 (s, 1H, pyrimidine-H), 5.87
(dd, J = 10.6 Hz, J = 20.8 Hz, 1H, PCH), 6.85–7.40 (m, 7H, ArH); 31P NMR (CDCl3,
162 MHz): δ 19.07; ESI-MS: m/z 635 (M++Na-1, 58), 615 (25), 613 (M+, 100). Anal.
Calcd for C26H30Cl2N3O8P: C, 50.83; H, 4.92; N, 6.84. Found: C, 50.57; H, 5.11; N,
6.53.
Data for 5g (Ar = 4-FC6H4, R = CH3, Rꢁ = C2H5): yield, 85%; white solid;
mp 139.9–141.1◦C; IR (KBr): ν 3428 (N H), 1693 (C O), 1401, 1211 (P O), 1034
1
(P O C), 984 (P C) cm−1; H NMR (CDCl3, 400 MHz): δ 1.15 (t, J = 6.8 Hz, 3H,
CH3), 1.31 (t, J = 7.2 Hz, 3H, CH3), 1.63 (d, J = 6.8 Hz, 3H, CH3), 3.80–4.14 (m, 4H,
2CH2), 3.83 (s, 6H, 2CH3O), 4.69 (q, J = 6.8 Hz, 1H, CH), 5.41 (dd, J = 10.6 Hz, J =
20.8 Hz, 1H, PCH), 5.79 (s, 1H, pyrimidine-H), 6.86–7.17 (m, 8H, ArH), 7.31 (s, 1H, NH);
31P NMR (CDCl3, 162 MHz): δ 18.55; ESI-MS: m/z 602 (M++K-1, 36), 585 (M++Na-1,
85), 563.7 (M+, 100). Anal. Cacld for C26H31FN3O8P: C, 55.42; H, 5.54; N, 7.46. Found:
C, 55.25; H, 5.39; N, 7.20.
Data for 5h (Ar = 4-ClC6H4, R = CH3, Rꢁ = C2H5): yield, 81%; white solid; mp
109.7–111.2◦C; 1H NMR (CDCl3, 600 MHz): δ 1.17 (t, J = 7.2 Hz, 3H, CH3), 1.31 (t, J =
7.2 Hz, 3H, CH3), 1.62 (d, J = 6.6 Hz, 3H, CH3), 3.81 (s, 6H, 2CH3O), 3.83–4.14 (m, 4H,
2CH2), 4.69 (q, J = 6.8 Hz, 1H, CH), 5.42 (dd, J = 10.8 Hz, J = 21.0 Hz, 1H, PCH), 5.79
(s, 1H, pyrimidine-H), 6.88 (d, J = 9.0 Hz, 2H, ArH), 7.11–7.27 (m, 6H, ArH), 7.32 (s,
1H, NH); 31P NMR (CDCl3, 243 MHz): δ 18.95; EI-MS (70ev): m/z 581(6), 579 (M+, 16),
139 (100). Anal. Calcd for C26H31ClN3O8P: C, 53.84; H, 5.39; N, 7.25. Found: C, 53.97;
H, 5.13; N, 7.40.

NOVEL PYRIMIDINYL DERIVATIVES
2321
Data for 5i (Ar = Ph, R = CH3, Rꢁ = n-C4H9): yield, 77%; white solid; mp
1
86.7–87.5◦C; H NMR (CDCl3, 400 MHz): δ 0.83 (t, J = 7.6 Hz, 3H, CH3), 0.93 (t,
J = 7.6 Hz, 3H, CH3), 1.22–1.45 (m, 8H, 2CH2CH2), 1.62 (d, J = 6.8 Hz, 3H, CH3),
3.62–4.12 (m, 4H, 2CH2), 3.85 (s, 6H, 2 CH3O), 4.68 (q, J = 6.8 Hz, 1H, CH), 5.45 (dd,
J = 10.8 Hz, J = 21.0 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.86 (d, J = 9.2 Hz,
2H, ArH), 7.10 (d, J = 9.2 Hz, 2H, ArH), 7.17–7.27 (m, 5H, ArH); 31P NMR (CDCl3, 162
MHz): δ 18.14; ESI-MS: m/z 639 (M++K-1, 22), 623.4 (M++Na-1, 64), 601.2 (M+, 100).
Anal. Calcd for C30H40N3O8P: C, 59.89; H, 6.70; N, 6.98. Found: C, 60.14; H, 6.69; N,
7.17.
Data for 5j (Ar = Ph, R = H, Rꢁ = C2H5): yield, 71%; yellow oil; 1H NMR (CDCl3,
400 MHz): δ 1.12 (t, J = 7.2 Hz, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3), 3.75–4.12 (m,
4H, 2CH2), 3.83 (s, 6H, 2CH3O), 4.54 (2d, J = 15.6 Hz, 2H, CH2), 5.55 (dd, J = 9.6 Hz,
J = 20.8 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.94 (d, J = 8.8 Hz, 2H, ArH), 7.17
(d, J = 8.8 Hz, 2H, ArH), 7.31–7.51 (m, 6H, ArH, NH); 31P NMR (CDCl3, 162 MHz): δ
19.79; ESI-MS: m/z 553 (M++Na-1, 64), 531 (M+, 100). Anal. Calcd for C25H30N3O8P:
C, 56.49; H, 5.69; N, 7.91. Found: C, 56.74; H, 5.48; N, 8.13.
Data for 5k (Ar = 4-CH3C6H4, R = H, Rꢁ = C2H5): yield, 69%; white solid; mp
86.9–88.2◦C; 1H NMR (CDCl3, 600 MHz): δ 1.14 (t, J = 7.2 Hz, 3H, CH3), 1.29 (t, J = 7.2
Hz, 3H, CH3), 2.33 (s, 3H, CH3), 3.75–3.77 (m, 1H, CH2), 3.84 (s, 6H, 2CH3O), 3.96–4.11
(m, 3H, 2CH2), 4.52 (2d, J = 15.6 Hz, 2H, CH2), 5.52 (dd, J = 9.6 Hz, J = 24.0 Hz, 1H,
PCH), 5.78 (s, 1H, pyrimidine-H), 6.95 (d, J = 9.0 Hz, 2H, ArH), 7.15–7.17 (m, 4H, ArH),
7.31 (d, J = 6.6 Hz, 2H, ArH), 7.44 (s, 1H, NH); 31P NMR (CDCl3, 243 MHz): δ 19.82;
ESI-MS: m/z 584 (M++K-1, 16), 567 (M++Na-1, 18), 545.0 (M+, 100). Anal. Calcd for
C26H32N3O8P: C, 57.24; H, 5.91; N, 7.70. Found: C, 57.40; H, 6.09; N, 7.42.
Data for 5l (Ar = 4-CH3OC6H4, R = H, Rꢁ = C2H5): yield, 76%; white solid; mp
82.4–84.1◦C; IR (KBr): ν 3428 (N H), 1696 (C O), 1404, 1205 (P O), 1024 (P O C),
1
981(P C) cm−1; H NMR (CDCl3, 400 MHz): δ 1.39 (t, J = 6.8 Hz, 3H, CH3), 1.29 (t,
J = 7.2 Hz, 3H, CH3), 3.76 (s, 3H, OCH3), 3.80 (s, 6H, 2CH3O), 3.84–4.12 (m, 4H, 2CH2),
5.52 (2d, J = 14.8 Hz, 2H, CH2), 5.50 (dd, J = 9.6 Hz, J = 20.4 Hz, 1H, PCH), 5.78 (s, 1H,
pyrimidine-H), 6.88 (d, J = 8.4 Hz, 2H, ArH), 6.95 (d, J = 8.8 Hz, 2H, ArH), 7.16 (d, J =
8.8 Hz, 2H, ArH), 7.41 (d, J = 8.5 Hz, 2H, ArH), 7.42 (s, 1H, NH); 31P NMR (CDCl3, 162
MHz): δ 19.30; ESI-MS: m/z 561.5 (M+, 100), 256.5 (14). Anal. Calcd for C26H32N3O9P:
C, 55.61; H, 5.74; N, 7.48. Found: C, 55.83; H, 5.91; N, 7.27.
Data for 5m (Ar = 4-ClC6H4, R = H, Rꢁ = C2H5): yield, 68%; yellow oil; 1H NMR
(CDCl3, 400 MHz): δ 1.16 (t, J = 6.8 Hz, 3H, CH3), 1.31 (t, J = 6.8 Hz, 3H, CH3), 3.86
(s, 6H, 2CH3O), 3.98–4.12 (m, 4H, 2CH2), 4.56 (2d, J = 14.8 Hz, 2H, CH2), 5.51 (dd,
J = 9.6 Hz, J = 23.0 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.96 (d, J = 8.8 Hz, 2H,
ArH), 7.17 (d, J = 8.4 Hz, 2H, ArH), 7.31–7.41(m, 4H, ArH), 7.43 (s, 1H, NH); 31P NMR
(CDCl3, 162 MHz): δ 19.86; ESI-MS: m/z 587 (M++Na-1, 37), 565.5 (M+, 100). Anal.
Calcd for C25H29ClN3O8P: C, 53.06; H 5.16; N, 7.42. Found: C, 52.81; H, 5.45; N, 7.28.
Data for 5n (Ar = 4-CH3C6H4, R = H, Rꢁ = CH3): yield, 72%; yellow oil; 1H NMR
(CDCl3, 400 MHz): δ 2.34 (s, 3H, CH3), 3.52 (d, J = 10.4 Hz, 3H, CH3), 3.72 (d, J =
10.8 Hz, 3H, CH3), 3.85(s, 6H, 2CH3O), 4.57 (2d, J = 14.0 Hz, 2H, CH2), 5.61 (dd, J =
9.6 Hz, J = 22.4 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.95 (d, J = 9.2 Hz, 2H,
ArH), 7.15–7.18 (m, 4H, ArH), 7.30 (d, J = 8.8 Hz, 2H, ArH), 7.51 (s, 1H, NH); 31P NMR
(CDCl3, 162 MHz): δ 22.03; ESI-MS: m/z 555 (M++K-1, 23), 539 (M++Na-1, 41), 517
(M+, 100). Anal. Calcd for C24H28N3O8P: C, 55.71; H, 5.45; N, 8.12. Found: C, 55.63; H,
5.20; N, 8.30.

2322
Z.-H. YU AND D.-Q. SHI
Data for 5o (Ar = 4-BrC6H4, R = H, Rꢁ = C2H5): yield, 64%; yellow oil; 1H NMR
(CDCl3, 400 MHz): δ 1.17 (t, J = 6.8 Hz, 3H, CH3), 1.30 (t, J = 6.8 Hz, 3H, CH3), 3.82
(s, 6H, 2CH3O), 3.98–4.12 (m, 4H, 2CH2), 4.54 (2d, J = 15.2 Hz, 2H, CH2), 5.49 (dd,
J = 9.6 Hz, J = 21.0 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.95 (d, J = 9.2 Hz, 2H,
ArH), 7.16 (d, J = 7.2 Hz, 2H, ArH), 7.28–7.51 (m, 5H, ArH, NH); 31P NMR (CDCl3,
162 MHz): δ 18.79; EI-MS (70ev): m/z 611(12), 609 (M+, 12.5), 275 (28), 139 (M+, 100),
111 (73). Anal. Calcd for C25H29BrN3O8P: C, 49.19; H, 4.79; N, 6.88. Found: C, 49.40;
H, 4.97; N, 7.05.
Data for 5p (Ar = 4-FC6H4, R = H, Rꢁ = C2H5): yield, 68%; yellow oil; 1H NMR
(CDCl3, 400 MHz): δ 1.15 (t, J = 7.2 Hz, 3H, CH3), 1.29 (t, J = 7.2 Hz, 3H, CH3), 3.84
(s, 6H, 2CH3O), 3.92–4.14 (m, 4H, 2CH2), 4.55 (2d, J = 15.2 Hz, 2H, CH2), 5.75 (dd,
J = 10.8 Hz, J = 21.4 Hz, 1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.94 (d, J = 8.8 Hz, 2H,
ArH), 6.96–7.05 (m, 2H, ArH), 7.17 (d, J = 8.8 Hz, 2H, ArH), 7.28–7.34 (m, 3H, ArH,
NH); 31P NMR (CDCl3, 162 MHz): δ 19.27; ESI-MS: m/z 587 (M++K-1, 72), 549 (M+,
100). Anal. Calcd for C25H29FN3O8P: C, 54.65; H, 5.32; N, 7.65. Found: C, 54.83; H, 5.11;
N, 7.47.
Data for 5q (Ar = Ph, R = H, Rꢁ = n-C4H9): yield, 61%; white solid; mp 76.1–77.0◦C;
1H NMR (CDCl3, 400 MHz): δ 0.83 (t, J = 7.2 Hz, 3H, CH3), 0.90 (t, J = 7.6 Hz, 3H,
CH3), 1.20–1.46 (m, 6H, CH2), 1.57–1.68 (m, 2H, CH2), 3.65–4.06 (m, 4H, 2CH2), 3.88
(s, 6H, 2CH3O), 4.55 (2d, J = 14.8 Hz, 2H, CH2), 5.56 (dd, J = 10.0 Hz, J = 20.6 Hz,
1H, PCH), 5.78 (s, 1H, pyrimidine-H), 6.95 (d, J = 8.8 Hz, 2H, ArH), 7.17 (d, J = 8.8
Hz, 2H, ArH), 7.29–7.47 (m, 5H, ArH). 7.50 (s, 1H, NH); 31P NMR (CDCl3, 162 MHz): δ
17.87; ESI-MS: m/z 624.7 (M++K-1, 12), 609.4 (M++Na-1, 27), 587.6 (M+, 100), 582.9
(13). Anal. Calcd for C29H38N3O8P: C, 59.28; H, 6.52; N, 7.15. Found: C, 59.47; H, 6.73;
N, 6.91.
Herbicidal Activity (In Vitro)
The herbicidal evaluation of compounds 5 were carried out in the laboratory of
biological activities test, State Key Laboratory of Elemento-organic Chemistry, Nankai
University. The results are summarized in Table S2 (Supplemental Materials).
Herbicidal Activity (In Vivo)
The herbicidal activities of some of compounds 5 were evaluated using a previously
reported procedure.19 See the Supplemental Materials for complete details.
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2323
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