Synthesis and herbicidal activity of α-hydroxy phosphonate derivatives containing pyrimidine moiety

Article abstract of DOI:10.1002/cjoc.201090337

A series of α-hydroxy phosphonate derivatives containing pyrimidine moiety were designed and synthesized. Their structures were characterized by IR, ¹H NMR, MS and elemental analysis. The results of preliminary herbicidal activities (in vitro)

Full text of DOI:10.1002/cjoc.201090337

FULL PAPER
Synthesis and Herbicidal Activity of α-Hydroxy Phosphonate
Derivatives Containing Pyrimidine Moiety
a,b
a,b
,a
Song, Hong (宋红)
Mao, Huiyu (毛会玉)
Shi, Deqing* (石德清)
a
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan, Hubei 430079, China
b
Wuhan Bioengineering Institute, Wuhan, Hubei 430415, China
A series of α-hydroxy phosphonate derivatives containing pyrimidine moiety were designed and synthesized.
1
Their structures were characterized by IR, H NMR, MS and elemental analysis. The results of preliminary herbi-
cidal activities (in vitro) showed that some of the title compounds 2 exhibited moderate herbicidal activities against
dicotyledonous weeds (Brassica campestris L), and most of compounds 2 showed better activity against dicoty-
ledonous weeds than monocotyledonous weeds (Echinochloa crus-galli). Further bioassays (in vivo) indicated that
some of the title compounds 2 possessed good and selective herbicidal activity against amaranth pigweed (A. retro-
flexus) in both pre- and post-emergence treatments at the dose of 1.5 kg/ha. For exmple, compounds 2a, 2b and 2e
exhibited 100% inhibition against A. retroflexus in pre-emergence treatment, and 91.7%, 98.8% and 99.5% inhibi-
tion in post-emergence treatment at the dose of 1.5 kg/ha, respectively.
Keywords α-hydroxy phosphonate, pyrimidinyl carboxylic acid, herbicidal activity, nitrogen heterocycle, phos-
phorus heterocycle
Introduction
The biological importance of phosphonates was
1
known for many years. Among them, α-hydroxy phos-
phonates are particularly important due to their remark-
2
able biological activities, such as enzyme inhibitors,
3
4
5
antibacterial agents, herbicides, anti-HIV agents,
6
,7
botryticides and haptens for catalytic antibodies. Re-
cently, pyrimidinyl carboxylic acid derivatives have
been found to be effective herbicides against barnyard
grass in different growth stages including pre-emerg-
ence treatment and excellent safety on transplanted rice
crops, animals and fish, etc. These herbicides, which are
known as inhibitors of branched chain amino acids syn-
thase (ALS or AHAS), have attracted considerable at-
8
-12
tention from the field of pesticide scientists.
To date,
several pyrimidyl carboxylic acid derivatives, such as
bispyribac-sodium and pyriminobac-methyl, have been
used as commercial herbicides (Figure 1). In our previ-
ous work, we synthesized a series of α-amino phospho-
nate derivatives containing pyrimidine moiety, and
some of them displayed moderate to good herbicidal
activity against amaranth pigweed (Amaranthus retro-
Figure 1 Structures of some commercial pyrimidinyl carboxylic
acid and pyrimidinyl benzylamine herbicides.
tionships, we have synthesized a series of novel α-hy-
droxy phosphonate derivatives containing pyrimidine
moiety 2 (Scheme 1). At first, compounds 2a—2e are
structurally similar to pyriminobac-methyl, but a phos-
phonyl group is attached instead of carboxylate group
according to bioisosterism; secondly, we hypothesize
that these compounds can be oxidized and further hy-
1
3
flexus). They are structurally similar to ZJ0273, a
1
4
prodrug herbicide invented and used in China. In order
to optimize the lead structures of pyrimidyl carboxylic
acid derivatives and study their structure-activity rela-
*
E-mail: chshidq@mail.ccnu.edu.cn; Tel.: 0086-027-67867958; Fax: 0086-027-67867955
Received January 31, 2010; revised March 18, 2010; accepted April 1, 2010.
Project supported by the National Natural Science Foundation of China (No. 20872046) and the Natural Science Foundation of Hubei Province (No.
2
008CDB086).
2020
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 2020— 2024

Synthesis and Herbicidal Activity of α-Hydroxy Phosphonate Derivatives
drolyzed to its carboxylic acid derivatives in plant or-
ganisms, so they might also work as a prodrug of
pyriminidyl carboxylic acid herbicides. Compounds
available and were used directly without further purifi-
cation. All solvents were dried and redistilled before
use.
2
f—2j are similar with 2a—2e, except pyrimidinyloxy
Synthesis of 2-(4,6-dimethoxypyrimidin-2-yloxy)-
benzoaldehyde (1a)
group in different position attached to benzene ring.
Their herbicidal activities against Brassica campestris L
and Echinochloa crus-galli (in vitro and in vivo) were
evaluated in this study.
Salicylaldehyde (1.22 g, 10 mmol), 4,6-dimethoxy-
pyrimidin-2-yl-methyl sulfoxide (2.18 g, 10 mmol) and
anhydrous potassium carbonate (2.07 g, 15 mmol) in dry
THF (15 mL) were stirred under reflux for 8 h. The
solid was filtered off, and the liquid was poured into ice
water (20 mL). The crude product was collected by fil-
tration. After recrystallization from ethanol/water (V∶V,
Scheme 1 Synthetic route of title compunds 2
1
9
∶1), a light yellow crystal was obtained (2.25 g), yield
1
4%, m.p. 61.5—62.5 ℃; H NMR (CDCl
3
, 600 MHz)
3
δ: 3.85 (s, 6H, 2OCH ), 5.84 (s, 1H, pyrimidine-H), 7.22
(
7
d, J＝7.8 Hz, 1H, ArH), 7.32 (t, J＝8.0 Hz, 2H, ArH),
.60 (d, J＝7.2 Hz, 1H, ArH), 9.78 (s, 1H, CHO). Anal.
12 2 4
cacld for C13H N O : C 60.00, H 4.65, N 10.76; found
C 59.82, H 4.51, N 10.97.
4
-(4,6-Dimethoxypyrimidin-2-yloxy)-benzoaldehyde
(
1b) was prepared in a similar procedure. Yield 87%,
1
light yellow solid, m.p. 73.3 — 74.2 ℃ ; H NMR
3 3
(CDCl , 600 MHz) δ: 3.85 (s, 6H, 2OCH ), 5.84 (s, 1H,
pyrimidine-H), 7.39 (d, J＝7.8 Hz, 2H, ArH), 7.94 (d,
J＝8.4 Hz, 2H, ArH), 10.01 (s, 1H, CHO). Anal. cacld
12 2 4
for C13H N O : C 60.00, H 4.65, N 10.76; found C
6
0.17, H 4.40, N 11.03.
General synthetic procedures for O,O'-dialkyl 1-
hydroxy-[2 or 4-(4,6-dimethoxypyrimidin-2-yloxy)-
phenyl]methylphosphonates (2)
Compounds 1 (2 mmol), dialkyl phosphite (2 mmol),
triethylamine (0.204 g, 2 mmol) in anhydrous methylene
chloride (10 mL) were stirred under reflux for 8—12 h
(monitored by TLC). After the removal of the solvent
followed by column chromatography of the crude prod-
uct on silica gel using a mixture of petroleum ether and
acetone (V∶V, 4∶1) as the eluent, compounds 2 were
obtained as colorless or light yellow crystals in 69%—
Experimental
Reagents and instruments
8
1
9% yields.
Melting points were determined on an X-4 binocular
microscope melting point apparatus (Beijing Tech In-
2
a (R＝CH
3
): Yield 88%, colorless crystal, m.p.
1
48.9—150.6 ℃; H NMR (CDCl
, 600 MHz) δ: 3.62
1
3
struments Co., Beijing, China) and uncorrected. H and
(
d, J＝10.8 Hz, 3H, CH
3
), 3.76 (d, J＝10.8 Hz, 3H,
3
1
P NMR spectra were performed on a Varian Mercury
Plus-400 (400 MHz) or Varian Mercury Plus-600 (600
MHz) spectrometer at room temperature in CDCl with
TMS and 85% H PO as the internal and external stan-
CH
3
), 3.82 (s, 6H, 2CH
3
O), 5.39 (d, J＝11.4 Hz, 1H,
CH), 5.79 (s, 1H, pyrimidine-H), 7.20 (d, J＝7.8 Hz, 1H,
3
ArH), 7.30 (t, J＝8.4 Hz, 1H, ArH), 7.35 (t, J＝7.2 Hz,
3
4
31
1
(
2
1
H, ArH), 7.78 (d, J＝7.2 Hz, 1H, ArH); P NMR
dards, respectively. 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. IR spectra were recorded on a Nicolet
NEXUS470 spectrometer as KBr pellets with absorption
CDCl
3
, 243 MHz) δ: 21.50; IR (KBr) ν: 3250 (O—H),
985 (Ar—H), 1600, 1572, 1470 (Ar), 1370 (C—O—C),
－1
225 (P＝O), 1062 (P—O—C), 985 (P—C) cm ;
＋
EI-MS (70 eV) m/z: 370 (M , 55.1), 258 (100), 243
(
(
7.3), 233 (33.0), 231 (54.1), 228 (32.5), 214 (7.7), 184
14.1), 162 (23.8), 138 (29.2), 111 (17.7), 109 (22.9), 90
－
1
(34.9), 76 (22.2). Anal. cacld for C15
19 2 7
H N O P: C 48.65,
given in cm . 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
H 5.17, N 7.57; found C 48.81, H 5.34, N 7.87.
2
b (R＝C
2 5
H ): Yield 87%, light yellow crystals, m.p.
1
1
(
48.0—149.7 ℃; H NMR (CDCl
3
, 600 MHz) δ: 1.16
t, J＝7.8 Hz, 3H, CH
3
), 1.28 (t, J＝7.2 Hz, 3H, CH
3
),
Chin. J. Chem. 2010, 28, 2020— 2024
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www.cjc.wiley-vch.de
2021

Song, Mao & Shi
FULL PAPER
3
3
5
.82 (s, 6H, 2CH
3
O), 3.93—3.95 (m, 1H, OCH
2
),
),
H), 7.19 (d, J＝8.4 Hz, 1H, ArH), 7.27 (t, J＝6.8 Hz,
1H, ArH), 7.33 (t, J＝6.8 Hz, 1H, ArH), 7.78 (d, J＝7.2
.99—4.03 (m, 1H, OCH
2
), 4.13—4.17 (m, 2H, OCH
2
3
1
.33 (d, J＝12.0 Hz, 1H, CH), 5.79 (s, 1H, pyrimidine-
3
Hz, 1H, ArH); P NMR (CDCl , 243 MHz) δ: 21.82; IR
H), 7.20 (d, J＝8.4 Hz, 1H, ArH), 7.29 (t, J＝7.2 Hz,
(KBr) ν: 3327 (O—H), 2997 (Ar—H), 1600, 1562, 1498
(Ar), 1366 (C—O—C), 1232 (P＝O), 1041 (P—O—C),
1
H, ArH), 7.35 (t, J＝7.8 Hz, 1H, ArH), 7.78 (d, J＝7.8
3
1
－1
＋
Hz, 1H, ArH); P NMR (CDCl
3
, 243 MHz) δ: 21.71; IR
984 (P—C) cm ; ESI (LC-MS) m/z: 492 (M ＋K－H,
＋
＋
(
(
9
3
2
KBr) ν: 3329 (O—H), 2991 (Ar—H), 1600, 1568, 1493
78.5), 476 (M ＋Na－H, 34.2), 454 (M , 100). Anal.
Ar), 1363 (C—O—C), 1221 (P＝O), 1062 (P—O—C),
31 2 7
cacld for C21H N O P: C 55.50, H 6.88, N 6.16; found
－
1
＋
72 (P—C) cm ; EI-MS (70 eV) m/z: 398 (M , 40.7),
81 (5.1), 366 (8.4), 256.5 (88.3), 242 (18.2), 233 (47.2),
31 (66.3), 228 (83.9), 201 (24.1), 185 (37.5), 172
C 55.36, H 7.09, N 6.23.
2f (R＝CH
3
): Yield 69%, colorless crystal, m.p.
1
101.0—102.1 ℃; H NMR (CDCl
3
, 400 MHz) δ: 3.68
(
1
19.2), 162 (30.6), 154 (30.1), 138 (98.4), 120 (53.1),
10 (100), 90 (45.2), 81 (66.1), 64 (38.0). Anal. cacld
P: C 51.26, H 5.82, N 7.03; found C
1.03, H 5.97, N 6.80.
(d, J＝10.4 Hz, 3H, CH
3
), 3.72 (d, J＝10.8 Hz, 3H,
CH
3
), 3.84 (s, 6H, 2CH
3
O), 5.09 (d, J＝10.8 Hz, 1H,
for C17
5
H
23
2
N O
7
CH), 5.79 (s, 1H, pyrimidine-H), 7.23 (d, J＝8.4 Hz, 2H,
3
1
ArH), 7.52 (d, J＝8.4 Hz, 2H, ArH); P NMR (CDCl
3
,
2
c (R＝i-Pr): Yield 85%, colorless crystal, m.p.
162 MHz) δ: 22.10; IR (KBr) ν: 3251 (O—H), 2980
1
1
03.0—103.9 ℃; H NMR (CDCl
3
, 600 MHz) δ: 1.06
(Ar—H), 1603, 1571, 1505 (Ar), 1368 (C—O—C),
－
1
(
1
CH
d, J＝6.0 Hz, 3H, CH
3
), 1.22 (d, J＝6.0 Hz, 3H, CH
3
),
1227 (P＝O), 1058 (P—O—C), 982 (P—C) cm ;
＋
.27 (d, J＝6.0 Hz, 3H, CH
3
), 1.30 (d, J＝6.6 Hz, 3H,
EI-MS (70 eV) m/z: 370 (M , 15.3), 353 (3.8), 260
3
), 3.82 (s, 6H, 2 CH
3
O), 4.59—4.62 (m, 1H, OCH),
(100), 229 (10.2), 185 (10.8), 109 (19.1), 90 (4.9), 69
4
.74—4.77 (m, 1H, OCH), 5.25 (d, J＝11.6 Hz, 1H,
19 2 7
(9.1). Anal. cacld for C15H N O P: C 48.65, H 5.17, N
CH), 5.78 (s, 1H, pyrimidine-H), 7.19 (d, J＝8.4 Hz, 1H,
7.57; found C 48.44, H 5.30, N 7.71.
ArH), 7.28 (t, J＝7.2 Hz, 1H, ArH), 7.34 (t, J＝7.2 Hz,
2g (R＝C
2 5
H ): Yield 88%, colorless crystal, m.p.
3
1
1
1
H, ArH), 7.81 (d, J＝7.8 Hz, 1H, ArH); P NMR
136.2—137.3 ℃; H NMR (CDCl
3
, 400 MHz) δ: 1.22
(CDCl
3
, 243 MHz) δ: 20.23; IR (KBr) ν: 3320 (O—H),
(t, J＝7.2 Hz, 3H, CH
3
), 1.27 (t, J＝6.8 Hz, 3H, CH
3
),
2
998 (Ar—H), 1604, 1560, 1497 (Ar), 1356 (C—O—C),
3.82 (s, 6H, 2CH
3
O), 4.04—4.08 (m, 4H, OCH
2
), 5.06
－
1
1
228 (P＝O), 1051 (P—O—C), 985 (P—C) cm ;
(d, J＝10.0 Hz, 1H, CH), 5.79 (s, 1H, pyrimidine-H),
＋
EI-MS (70 eV) m/z: 426 (M , 45.5), 367 (9.7), 324
7.22 (d, J＝8.4 Hz, 2H, ArH), 7.52 (d, J＝8.4 Hz, 2H,
3
1
(27.6), 256 (96.9), 243 (16.9), 231 (100), 228 (58.6),
3
ArH); P NMR (CDCl , 162 MHz) δ: 21.86; IR (KBr) ν:
214 (12.0), 200.5 (30.0), 184 (20.7), 168 (12.2), 162
3356 (O—H), 2984 (Ar—H), 1601, 1575, 1508, 1474
(Ar), 1370 (C—O—C), 1224 (P＝O), 1057 (P—O—C),
(51.1), 154 (14.8), 138 (41.0), 123 (37.1), 109 (39.1),
－
1
＋
103 (15.6), 91 (50.0), 81 (53.6), 76 (24.0), 69 (20.1),
57.5 (26.4). Anal. cacld for C19 P: C 53.52, H
6.38, N 6.57; found C 53.73, H 6.47, N 6.33.
979 (P—C) cm ; EI-MS (70 eV) m/z: 398 (M , 43.0),
381 (14.3), 352 (7.8), 257 (95.5), 243 (25.0), 228 (49.0),
184.5 (51.0), 162 (25.1), 138 (70.5), 119 (43.9), 110
(100), 104 (21.1), 90 (29.0), 84 (32.4), 81 (82.0), 76
27 2 7
H N O
2
d (R＝n-Pr): Yield 89%, light yellow crystal, m.p.
1
6
7.4—68.4 ℃; H NMR (CDCl
3
, 600 MHz) δ: 0.81 (t,
23 2 7
(24.9), 64 (27.7). Anal. cacld for C17H N O P: C 51.26,
H 5.82, N 7.03; found C 51.54, H 5.91, N 7.18.
J＝7.2 Hz, 3H, CH
3
), 0.90 (t, J＝7.2 Hz, 3H, CH
3
2
2
2
),
),
),
),
1
3
3
5
.51—1.55 (m, 2H, CH
2
), 1.63—1.66 (m, 2H, CH
2h (R＝i-Pr): Yield 77%, colorless crystal, m.p.
1
.81 (s, 6H, 2CH
3
O), 3.82—3.85 (m, 1H, OCH
103.0—104.8 ℃; H NMR (CDCl
3
, 400 MHz) δ: 1.14
.89—3.91 (m, 1H, OCH
2
), 4.02—4.05 (m, 2H, OCH
(d, J＝6.0 Hz, 3H, CH
3
), 1.25—1.30 (2d, J＝6.4 Hz, 9H,
.35 (d, J＝11.4 Hz, 1H, CH), 5.79 (s, 1H, pyrimidine-
CH
3
), 3.82 (s, 6H, 2CH
3
O), 4.61—4.67 (m, 2H, OCH),
H), 7.19 (d, J＝7.2 Hz, 1H, ArH), 7.28 (t, J＝7.2 Hz,
5.00 (d, J＝10.8 Hz, 1H, CH), 5.78 (s, 1H, pyrimidine-
1
H, ArH), 7.33 (t, J＝6.6 Hz, 1H, ArH), 7.79 (d, J＝6.6
H), 7.20 (d, J＝8.8 Hz, 2H, ArH), 7.52 (d, J＝8.8 Hz,
3
1
31
Hz, 1H, ArH); P NMR (CDCl
3
, 243 MHz) δ: 21.18; IR
2H, ArH); P NMR (CDCl
3
, 162 MHz) δ: 21.73; IR
(
(
9
5
KBr) ν: 3318 (O—H), 2992 (Ar—H), 1601, 1565, 1495
(KBr) ν: 3253 (O—H), 2982 (Ar—H), 1604, 1573, 1507,
Ar), 1350 (C—O—C), 1236 (P＝O), 1045 (P—O—C),
1472 (Ar), 1372 (C—O—C), 1226 (P＝O), 1060
－
1
＋
－1
82 (P—C) cm ; ESI (LC-MS) m/z: 464 (M ＋K－H,
(P—O—C), 986 (P—C) cm ; EI-MS (70 eV) m/z:
＋
＋
＋
8.2), 448 (M ＋Na－1, 76.4), 426 (M , 100). Anal.
426.5 (M , 42.5), 409 (8.9), 383 (8.0), 366.5 (16.2), 256
cacld for C19
C 53.37, H 6.12, N 6.70.
H
27
N
2
O
7
P: C 53.52, H 6.38, N 6.57; found
(85.8), 228 (39.2), 199 (8.4), 185 (37.7), 162 (19.2), 139
(18.2), 123 (100), 109 (52.7), 90 (21.6), 83.5 (27.5), 81
2
e (R＝n-Bu): Yield 80%, light yellow crystals, m.p.
27 2 7
(74.6), 64 (18.5). Anal. cacld for C19H N O P: C 53.52,
H 6.38, N 6.57; found C 53.35, H 6.51, N 6.80.
1
3
8.9—39.5 ℃; H NMR (CDCl
3
, 600 MHz) δ: 0.84 (t,
J＝7.2 Hz, 3H, CH
3
), 0.89 (t, J＝7.2 Hz, 3H, CH
3
),
2
),
2
),
2
),
2
),
2i (R＝n-Pr): Yield 82%, colorless crystal, m.p.
1
1
1
3
3
5
.23—1.27 (m, 2H, CH
2
), 1.32—1.36 (m, 2H, CH
), 1.58—1.61 (m, 2H, CH
75.0—76.4 ℃; H NMR (CDCl
3
, 400 MHz) δ: 0.85 (t,
.47—1.49 (m, 2H, CH
2
J＝7.2 Hz, 3H, CH
3
), 0.90 (t, J＝7.2 Hz, 3H, CH
3
),
.81 (s, 6H, 2CH
3
O), 3.83—3.87 (m, 1H, OCH
1.57—1.65 (m, 4H, CH
2
), 3.82 (s, 6H, 2CH
3
O), 3.88—
.93—3.95 (m, 1H, OCH
2
), 4.06—4.09 (m, 2H, OCH
3.98 (m, 4H, OCH
2
), 5.07 (d, J＝10.4 Hz, 1H, CH),
.33 (d, J＝11.4 Hz, 1H, CH), 5.79 (s, 1H, pyrimidine-
5.78 (s, 1H, pyrimidine-H), 7.20 (d, J＝8.0 Hz, 2H,
2
022
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 2020— 2024

Synthesis and Herbicidal Activity of α-Hydroxy Phosphonate Derivatives
3
1
ArH), 7.51 (d, J＝8.0 Hz, 2H, ArH); P NMR (CDCl
3
,
with chemical shift δ 5.8 and 3.8, respectively, and the
hydroxy protons of all compounds 2 have not be found
in their H NMR spectra. IR spectra of compounds 2
1
(
62 MHz) δ: 21.34; IR (KBr) ν: 3263 (O—H), 2977
1
Ar—H), 1606, 1571, 1500, 1472 (Ar), 1369 (C—O—
－
1
C), 1228 (P＝O), 1058 (P—O—C), 981 (P—C) cm ;
showed normal stretching absorption bands, indicating
＋
－1
EI-MS (70 eV) m/z: 426 (M , 35.5), 409 (12.4), 366.5
the existence of OH (ca. 3250 cm ), Ar—H (ca. 2980
－
1
－1
(
(
(
7.8), 257 (89.9), 246 (23.0), 228 (48.5), 185 (41.8), 138
cm ), Ar (ca. 1600, ca. 1570, ca. 1470 cm ), P＝O
－
1
－1
16.3), 124 (84.5), 119 (47.8), 109 (20.5), 90 (22.1), 81
100), 76 (23.4), 64 (22.5). Anal. cacld for C19
C 53.52, H 6.38, N 6.57; found C 53.70, H 6.34, N 6.69.
(ca. 1225 cm ), P—O—C (ca. 1060 cm ), P—C (ca.
－
1
H
27
N
2
O
7
P:
980 cm ). The EI or ESI mass spectra of compounds 2
revealed the existence of the moderate or strong mo-
lecular ion peaks and anticipant fragmentation peaks,
which were in good accordance with the given struc-
tures of products 2.
2
j (R＝n-Bu): Yield 77%, colorless crystals, m.p.
1
3
0
1
4
8.0—39.0 ℃; H NMR (CDCl
3
, 400 MHz) δ: 0.86—
.92 (m, 6H, CH
3
), 1.30—1.38 (m, 4H, CH
2
), 1.53—
.62 (m, 4H, CH
2
), 3.83 (s, 6H, 2CH
3
O), 3.88—4.01 (m,
Herbicidal activities
H, OCH
2
), 5.06 (d, J＝10.4 Hz, 1H, CH), 5.79 (s, 1H,
pyrimidine-H), 7.23 (d, J＝8.0 Hz, 2H, ArH), 7.51 (d,
The preliminary herbicidal activity (in vitro) of
compounds 2 against Brassica campestris L. (rape) and
Echinochloa crus-galli (barnyard grass) has been inves-
tigated at the concentrations of 100 and 10 mg/L com-
pared with the commercially available herbicide, Bis-
pyribac-sodium. The results showed that some of the
title compounds exhibited moderate herbicidal activities
against dicotyledonous weeds (Brassica campestris L)
at the concentration of 100 mg/L, and most of com-
pounds 2 showed higher activity against Brassica
campestris L. than Echinochloa crus-galli. For example,
compounds 2e, 2i and 2j exhibited higher herbicidal
activity than the control drug with the inhibition of
72.3%, 75.7% and 76.4%, respectively. However, all
compounds 2 showed weak herbicidal activities against
both mono- and dicotyledonous plants at the concentra-
tion of 10 mg/L. Further bioassays (in vivo) indicated
that some of title compounds possessed good and selec-
tive herbicidal activity against amaranth pigweed (A.
retroflexus) in both pre- and post-emergence treatments
at the dose of 1.5 kg/ha. For exmple, compounds 2a, 2b
and 2e exhibited 100% inhibition against A. retroflexus
in pre-emergence treatment, and 91.7%, 98.8% and
99.5% inhibition in post-emergence treatment at the
dose of 1.5 kg/ha, respectively. However, the title com-
pounds 2 exhibited weak herbicidal activities against
other plants such as B. campestris, E. crus-galli and D.
sanguinalis in both pre- and post-emergence treatments.
For the preliminary structure-activity relationships, as
seen from Tables 1 and 2, the different subtituted posi-
tions of pyrimidinyloxy group in benzene ring have
great influence on the herbicidal activity. Those com-
pounds with ortho-substituted one (2a—2e) showed
better herbicidal activity than those with para-sub-
stituted, the results are in good accordance with the
structure why most of commercial pyrimidyl carboxylic
acid herbicides are ortho-substituted, and also implied
that any introduction of pyrimidinyloxy group to the
para-position in benzene ring are not useful for the im-
provement of herbicidal activity. Moreover, different
phosphonyl groups have some influence on their herbi-
cidal activity. For example, those compounds (R＝n-Bu,
n-Pr) have better activities. This results are consistent
3
1
J＝6.8 Hz, 2H, ArH); P NMR (CDCl
3
, 162 MHz) δ:
1
1
(
(
9.86; IR (KBr): ν 3264 (O—H), 2992 (Ar—H), 1605,
501, 1467 (Ar), 1373 (C—O—C), 1224 (P＝O), 1061
－
1
P—O—C), 978 (P—C) cm ; ESI (LC-MS) m/z: 492
＋
＋
M ＋K－H, 58.7), 454 (M , 100). Anal. cacld for
21 31 2 7
C H N O P: C 55.50, H 6.88, N 6.16; found C 55.31,
H 6.73, N 5.99.
Herbicidal activity (in vitro)
The herbicidal evaluation of compounds 2 were car-
ried out in the laboratory of biological activities test
State Key Laboratory of Elemento-organic Chemistry,
Nankai University). Compounds 2 were determined
with Brassica campestris L. and Echinochloa crus-galli
as samples of annual dicotyledonous and monocotyle-
donous plants, respectively, using a previously reported
procedure. For all of the bioassay tests, each treatment
was repeated twice. The herbicidal activity is summa-
rized in Table 1.
(
1
5
Herbicidal activity (in vivo)
The herbicidal activities of some of compounds 2
were evaluated using a previously reported proce-
1
3,16
dure.
The herbicidal activity is listed in Table 2.
Results and discussion
Synthesis
4
,6-Dimethoxypyrimidin-2-yl-methylsulfone reacted
with salicylaldehyde or 4-hydroxybenzaldehyde in the
presence of potasium carbonate to yield 2-(4,6-dimeth-
oxypyrimidin-2-yloxy)benzaldehyde (1a), or 4-(4,6-
dimethoxypyrimidin-2-yloxy)benzaldehyde (1b) in
good yields. The target compounds 2 were synthesized
via the nucleophilic additions of various phosphites with
pyrimidinylsubstituted benzaldehyde 1a and 1b in the
presence of triethylamine in mild condition. Their
structures were characterized by spectroscopic data (IR,
H NMR, P NMR, MS) and elemental analyses. In the
H NMR spectra of 2, the methine proton linking with
phosphonyl group displayed as a doublet with the cou-
pling constants of 11.0 Hz, respectively. The pyrimidine
proton and two methoxy groups all exhibited as a singlet
1
1
31
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2023

Song, Mao & Shi
FULL PAPER
a
Table 1 The herbicidal activities of compounds 2a— 2j
B. campestris root test
E. crus-galli cup test
Compd.
1
00 mg/L
54.4
65.2
56.1
61.4
72.3
25.7
49.1
58.4
75.7
76.4
69.8
10 mg/L
44.8
61.4
28.0
23.8
55.1
6.1
100 mg/L
38.1
10 mg/L
6.2
2
a
2
b
48.6
22.1
0
2
c
27.6
2
d
23.6
23.0
0.7
2
e
60.9
2
f
23.8
0
2
g
14.5
9.8
24.1
0.7
2
h
38.1
6.2
2
i
34.6
21.5
65.6
29.8
3.4
2
j
29.9
0.7
Bispyribac-sodium
72.4
46.9
a
in vitro, percent inhibition, %.
a
Table 2 The herbicidal activities of some of compounds 2
Pre-emergence treatment
B. campestris A. retroflexus E. crus-galli D. sanguinalis
Post-emergence treatment
B. campestris A. retroflexus E. crus-galli D. sanguinalis
Compd.
2
a
48.6
55.3
36.4
100
100
100
48.6
32.5
0
79.3
66.4
81.4
29.8
50.2
48.9
91.7
98.8
99.5
69.2
65.7
51.6
16.0
20.0
15.0
2
b
2
e
Bispyribac-
sodium
9
9.9
100
95.5
96.7
100
100
100
100
a
in vivo, dosage:1.5 kg/ha, precent inhibition, %.
with the reported result, although the reason is very
clear. Further exploring of structure-activity relation-
ships needs more experimental results to support.
10 Tamaru, M.; Inoue, J.; Hanai, R. J. Agric. Food Chem. 1997,
1
7
45, 2777.
11 Tamaru, M.; Takehi, T.; Masuyama, N.; Hanai, R. J. Pestic.
Sci. 1996, 47, 327.
1
2
The Pesticide Manual, A World Compendium, 14th Edition,
Ed.: Tomlin, C. D. S., British Crop Production Council,
Hampshire, UK, 2006, p. 911.
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(E1001312 Ding, W.)
2
024
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Chin. J. Chem. 2010, 28, 2020— 2024