Synthesis and herbicidal activity of novel N-(2-fluoro-5(3-methyl-2,6- dioxo-4-(trifluoromethyl)-2,3-dihydro-pyrimidin-1(6H)-yl)phenyl) -2-phenoxyacetamide derivatives

Article abstract of DOI:10.1002/cjoc.201180410

Thirteen novel N-(2-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3- dihydropyrimidin-1(6H)-yl)phenyl)-2-phenoxy)acetamides were designed and synthesized utilizing 4-fluoro-aniline and ethyl 3-amino-4,4,4-trifluoro-but-2- enoate as starting materials

Full text of DOI:10.1002/cjoc.201180410

FULL PAPER
Synthesis and Herbicidal Activity of Novel N-(2-Fluoro-5(3-
methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-pyrimidin-
1(6H)-yl)phenyl)-2-phenoxyacetamide Derivatives
Wu, Daoxina(吴道新)
Sun, Jionga(孙炯)
Huang, Mingzhi*,b(黄明智)
Mo, Hongboc(莫洪波)
Wang, Xiaoguangb(王晓光)
Li, Hongweic(李宏伟)
Ren, Yeguob(任叶果)
Hu, Zhibingb(胡志彬)
He, Lianb(何莲)
Yin, Dulinb(尹笃林)
a School of Chemistry and Biological Engineering, Changsha University of Science and Technology, Changsha,
Hunan 410114, China
b National Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry,
Changsha, Hunan 410007, China
c Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of
China), Hunan Normal University, Changsha, Hunan 410081, China
Thirteen novel N-(2-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-1(6H)-yl)phenyl)-
2-phenoxy)acetamides were designed and synthesized utilizing 4-fluoro-aniline and ethyl 3-amino-4,4,4-trifluoro-
but-2-enoate as starting materials. The chemical structures of all compounds were confirmed by 1H NMR, IR, mass
spectrum and elemental analyses. Subsequently, the herbicidal activities of the as-prepared compounds were evalu-
ated in the greenhouse. Bioassay results indicated that most of compounds had better herbicidal activities against
dicotyledonous weeds. Among all the tested compounds, compounds 4a— 4i showed good herbicidal activities at
both pre-emergence and post-emergence treatment against two or three kinds of dicotyledonous weeds, such as
Abutilon theophrasti Medic, Amaranthus ascendens L, and Chenopodium album L at the dosage of 75 g ai/ha.
Keywords synthesis design, 2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidine, N-phenyl-2-phenoxyacetamide,
synthesis, herbicidal activity
Introduction
Cassia obtusifolia, Chenopodium album, Chyrsanthe-
mum segetum, Daturastramonium, Digitaria sangui-
nalis, Echinochloa crusgalli, Galium aparine, Matri-
caria chamomilla, Setariafaberii, Sinapis arvensis and
Xanthium pennsylvanicum, and diverse crops, such as
cape, soya, cotton, rice, wheat and maize crops. Ben-
zfendizone, when applied to post-emergence, provides
control of dicotyledon weeds in orchards and no-till
crop situations.6
The uracil-type herbicide has a substituted-
pyrimidine-2,6-dione as common structural feature.7 It
has been recognized that the optimal substituent in
pyrimidine-2,6-dione is trifluoromethyl group at
4-position, methyl at 3-position and multi-functiona-
lized phenyl at 1-position. The trifluoromethyl group is
the most favorable substituent, and enhances herbicidal
activity markedly. The optimal substituent in the phenyl
ring is halogen atoms like fluorine or chlorine at
It is well known that uracil derivatives have impor-
tant biological activities.1 The uracil derivatives are
more often used as antiphotosynthetic herbicides to
control weeds in cotton, sugar beet, turnip, soya, pea,
sunflower crop, vineyard, berry plantation, and
orchard.2 The uracil analog 1 discovered by the
Hoffman-La Roche group in 1986,3 which bears a
highly functionalized phenyl group and a trifluoro
methyl group at 4-position, is thought to be the first
example of 6-membered cyclic imide with protoporhy
rinogen oxidase (protox) inhibiting activity. Since then,
structural modifications of 4-trifluoromethyluracils have
been aggressively investigated. Among them, buta-
fenacil 24 and benzfendizone 35 shown in Figure 1 have
been developed as commercial herbicides. Butafenacil
is used for the control of weeds including weeds grasses,
such as Abutilon theophrasti, Amaranthus retroflexus,
*
E-mail: huang-mz@163.com; Tel.: 0086-0731-85959096; Fax: 0086-0731-85959000
Received December 9, 2010; revised March 18, 2011; accepted July 17, 2011.
Project supported by the National Natural Science Foundation of China (No. 20872033), Hunan Provincial Natural Science Foundation of China
(No. 07JJ1003) and Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China) (No.
KLCBTCMR2008-14).
Chin. J. Chem. 2011 29 2401— 2406
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Wu et al.
FULL PAPER
Figure 1 Typical protox inhibiting herbicides commercialized.
o-/p-position to uracil ring. It is interesting that the sub-
stituent at m-position of benzene ring often affects ef-
fectually the herbicidal activity and crop selectivity of
uracil. Most of the modifications and optimizations have
been focused on the substituent at m-position.8 The
typical uracils with N-modified phenyl ring systems are
presented in Figure 2.9-12
uracils and phenoxy carboxylic acids as depicted in
Figure 3. Their chemical structures were characterized
by H NMR, IR, mass spectroscopy, and elemental
analysis. Their herbicidal activities against dicotyledon
weeds at pre- and post-emergence were determined in
the greenhouse.
1
Experimental
Proton NMR spectra were obtained with a Varian
INOVA300 spectrometer using tetramethylsilane (TMS)
as internal standard and deuterochloroform as solvent.
LC-mass spectra were recorded with an HP 1100
LC-MS (APCI) using positive ion scan mode. IR spectra
were recorded in potassium bromide disks with a PE
System 2000 FTIR spectrophotometer. Elemental
analyses were carried out with a PE CHNS/O 2400 II
elemental analyzer. Uncorrected melting points were
taken on a WRS-1 melting point apparatus.
General procedure for the preparation of the 4a—
4m
Figure 2 Typical uracils with N-modified phenyl ring systems.
A mixture of 3.03 g (10.00 mmol) 3-(3-amino-4-
fluorophenyl)-1-methyl-6-(trifluoromethyl)-pyrimidine-
2,4(1H,3H)-dione (10) and 1.22 g (12.00 mmol)
triethylamine in toluene (25 mL) was stirred, then
measured 2-phenoxypropanoyl chloride or 2-phen-
oxyacetyl chloride (12 mmol) was added dropwise to
the mixture at 0—5 ℃. The reaction was carried
through at room temperature, and the end point of reac-
tion was tested by TLC. The deposit was filtrated, and
filtrate was poured into ice water (80 mL), and extracted
with ethyl acetate (25 mL×3). The incorpo-
rated organic layer was washed sequentially with dis-
tilled water, saturated sodium bicarbonate solution
The phenoxyacetic herbicides belong to synthetic
auxins, which are widely used to control dicotyledon
weeds in grass crops such as wheat, corn, sorghum, for-
ages and turf grasses. One member of this group,
2,4-D,13 is one of the first selective herbicides devel-
oped.
In our previous work, we introduced amide structure
into uracil.14-16 In order to find new lead compounds as
potential agrochemicals, in the present paper novel
N-(2-fluoro-5(3-methyl-2,6-dioxo-4-(trifluoromethyl)-2,
3-dihydro-pyrimidin-1(6H)-yl)phenyl)-2-phenoxy)acet-
amides (4) were designed and synthesized, which were
combined by the active moieties of 4-trifluoromethyl-
Figure 3 Design strategy for the target compounds.
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2401— 2406

Synthesis and Herbicidal Activity of Novel Derivatives
Figure 4 General synthetic route for the target compounds 4.
and brine, dried over anhydrous magnesium sulfate, and
concentrated in vacuo. The residue was purified by
column chromatography on silica gel using 4∶1 petro-
leum ether (b.p. 60—90 ℃)/ethyl acetate as the eluent
to yield target compounds 4a—4m as white solid or
yellow solid.
Anal. calcd for C22H19F4N3O4: C 56.78, H 4.11, N 9.03;
found C 56.81, H 4.15, N 9.07.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydropyrimidin-1(6H)-yl)phenyl)-2-(p-
tolyloxy)propanamide (4d) White solid, yield 88%,
m.p. 131.5—132.3 ℃ [V(petroleum ether)∶V(ethyl
acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ: 8.65 (s,
1H, NH), 8.40—8.43 (m, 1H, ArH), 7.25—7.77 (m, 2H,
ArH), 6.75—6.94 (m, 4H, ArH), 6.36 (s, 1H, ＝CH),
4.79 (q, J＝5.3 Hz, 1H, CH), 3.54 (s, 3H, NCH3), 2.30
2-(2,4-Dichlorophenoxy)-N-(2-fluoro-5-(3-methyl-
2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-pyrimidin-
1(6H)-yl)phenyl) propanamide (4a) Yellow solid,
yield 85%, m.p. 292.8 — 293.5 ℃ [V(petroleum
1
ether)∶V(ethyl acetate)＝5∶1]; H NMR (CDCl3, 300
(s, 3H, ArCH3), 1.63 (d, J＝6.9 Hz, 3H, CHCH3); IR
－ 1
MHz) δ: 8.96 (s, 1H, NH), 8.42 (q, J＝2.3 Hz, 1H, ArH),
7.45 (d, J＝2.7 Hz, 1H, ArH), 7.20—7.24 (m, 2H, ArH),
6.89—6.98 (m, 2H, ArH), 6.36 (s, 1H, ＝CH), 4.82 (q,
J＝5.3 Hz, 1H, CH), 3.53 (s, 3H, NCH3), 1.68 (d, J＝
6.6 Hz, 3H, CHCH3); IR (KBr) ν: 1728, 1685 (C＝O),
(KBr) ν: 1732, 1689 (C＝O), 3392 (N—H) cm
;
LC-MS (positive ion) m/z (%): 466 [(M＋1)＋, 100].
Anal. calcd for C22H19F4N3O4: C 56.78, H 4.11, N 9.03;
found C 56.69, H 4.16, N 9.08.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydro-pyrimidin-1(6H)-yl)phenyl)-2-
－1
3400 (N—H) cm ; LC-MS (positive ion) m/z (%): 520
[(M＋1)＋, 100]. Anal. calcd for C21H15Cl2F4N3O4: C
48.48, H 2.91, N 8.08; found C 48.39, H 2.97, N 8.17.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydro-pyrimidin-1(6H)-yl)phenyl)-2-
(2-methoxyphenoxy)propanamide (4b) Yellow solid,
yield 89%, m.p. 66.5—67.0 ℃ [V(petroleum ether)∶
V(ethyl acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ:
9.47 (s, 1H, NH), 8.44 (q, J＝1.5 Hz, 1H, ArH), 7.19—
7.26 (m, 1H, ArH), 6.88—7.06 (m, 5H, ArH), 6.35 (s,
1H, ＝CH), 4.71 (q, J＝1.5 Hz, 1H, CH), 3.90 (s, 3H,
OCH3), 3.53 (s, 3H, NCH3), 1.68 (d, J＝6.9 Hz, 3H,
CHCH3); IR (KBr) ν: 1732, 1688 (C＝0), 3345 (N—H)
(3-fluorophenoxy)propanamide (4e)
White solid,
yield 85%, m.p. 105.5 — 106.2 ℃ [V(petroleum
1
ether)∶V(ethyl acetate)＝5∶1]; H NMR (CDCl3, 300
MHz) δ: 8.53 (s, 1H, NH), 8.95 (dd, J＝2.7, 2.9 Hz, 1H,
ArH), 7.30 (d, J＝6.9 Hz, 1H, ArH), 7.25 (s, 1H, ArH),
7.20—7.24 (m, 1H, ArH), 6.91—6.96 (m, 1H, ArH),
6.69—6.79 (m, 3H, ArH), 6.36 (s, 1H, ＝CH), 4.79 (q,
J＝5.3 Hz, 1H, CH), 3.54 (s, 3H, NCH3), 1.65 (d, J＝
6.9 Hz, 3H, CHCH3); IR (KBr) ν: 1730, 1685 (C＝O),
3415 (N—H)－; LC-MS (positive ion) m/z (%): 470 [(M＋
＋
1
1) , 100] cm . Anal. calcd for C21H16F5N3O4: C 53.74,
H 3.44, N 8.95; found C 53.79, H 3.39, N 8.89.
＋
－1
cm ; LC-MS (positive ion) m/z (%): 482 [(M＋1) ,
100]. Anal. calcd for C22H19F4N3O5: C 56.89, H 3.98, N
8.73; found C 56.95, H,3.87, N 8.64.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydro-pyrimidin-1(6H)-yl)phenyl)-2-
phenoxypropanamide (4f) Yellow solid, yield 87%,
m.p. 136.1—136.8 ℃ [V(petroleum ether)∶V(ethyl
acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ: 8.65 (s,
1H, NH), 8.42 (q, J＝2.3 Hz, 1H, ArH), 7.33 (t, J＝1.8
Hz, 2H, ArH), 7.20—7.26 (m, 1H, ArH), 7.05 (t, J＝1.5
Hz, 1H, ArH), 6.90—6.95 (m, 3H, ArH), 6.37 (s, 1H,
＝CH), 4.80 (q, J＝5.3 Hz, 1H, CH), 3.55 (s, 3H,
NCH3), 1.65 (d, J＝6.6 Hz, 3H, CHCH3); IR (KBr) ν:
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydropyrimidin-1(6H)-yl)phenyl)-2-
(m-tolyloxy)propanamide (4c) Yellow solid, yield
89%, m.p. 115.8—116.5 ℃ [V(petroleum ether)∶
V(ethyl acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ:
8.65 (s, 1H, NH), 8.40—8.43 (m, 1H, ArH), 7.01—7.25
(m, 3H, ArH), 6.85—6.91 (m, 3H, ArH), 6.36 (s, 1H,
＝CH), 4.75 (q, J＝5.3 Hz, 1H, CH), 3.54 (s, 3H,
NCH3), 2.35 (s, 3H, ArCH3), 1.63 (d, J＝6.6 Hz, 3H,
CHCH3); IR (KBr) ν: 1731, 1692 (C＝O), 3345 (＋N—H)
－ 1
1731, 1682 (C＝O), 3376 (N—H) cm ; LC-MS
(positive ion) m/z (%): 452 [(M＋1)＋, 100]. Anal. calcd
for C21H17F4N3O4: C 55.88, H 3.80, N 9.31; found C
55.79, H 3.85, N 9.40.
－1
cm ; LC-MS (positive ion) m/z (%): 466 [(M＋1) , 100].
Chin. J. Chem. 2011, 29, 2401— 2406
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Wu et al.
FULL PAPER
2-(4-Chloro-3-methylphenoxy)-N-(2-fluoro-5-(3-
methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-
pyrimidin-1(6H)-yl)phenyl)propanamide (4g) Yel-
low solid, yield 86%, m.p. 70.3—71.2 ℃ [V(petroleum
1(6H)-yl)phenyl)propanamide (4k)
Yellow solid,
yield 90%, m.p. 97.4—98.7 ℃ [V(petroleum ether)∶
V(ethyl acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ:
8.65 (s, 1H, NH), 8.43 (q, J＝2.3 Hz, 1H, ArH), 7.52—
7.57 (m, 1H, ArH), 7.39—7.45 (m, 1H, ArH), 7.29—
7.35 (m, 1H, ArH), 7.18—7.25 (m, 1H, ArH), 7.02—
7.07 (m, 1H, ArH), 6.90—6.95 (m, 1H, ArH), 6.36 (s,
1H, ＝CH), 4.84 (q, J＝5.3 Hz, 1H, CH), 3.54 (s, 3H,
NCH3), 1.67 (d, J＝6.6 Hz, 3H, CHCH3); IR (KBr) ν:
1
ether)∶V(ethyl acetate)＝5∶1]; H NMR (CDCl3, 300
MHz) δ: 8.57 (d, J＝1.8 Hz, 1H, NH), 8.40 (q, J＝2.3
Hz, 1H, ArH), 7.24—7.28 (m, 1H, ArH), 7.18—7.22 (m,
1H, ArH), 6.90—6.96 (m, 1H, ArH), 6.85 (d, J＝3.0 Hz,
ArH), 6.73—6.77 (m, 1H, ArH), 6.36 (s, 1H, ＝CH),
4.74 (q, J＝5.3 Hz, 1H, CH), 3.54 (d, J＝1.2 Hz, 3H,
NH3), 2.36 (s, 3H, ArCH3), 1.62 (d, J＝6.9 Hz, 3H,
CHCH3); IR (KBr) ν: 1731, 1691 (C＝O), 3412 (N—H)
－ 1
1731, 1687 (C＝O), 3410 (N—H) cm ; LC-MS
(positive ion) m/z (%): 528 [(M＋1)＋, 100]. Anal. calcd
for C27H21F4N3O4: C 61.48, H 4.01, N 7.97; found C
61.59, H 4.09, N 7.91.
＋
－1
cm ; LC-MS (positive ion) m/z (%): 500 [(M＋1) ,
100]. Anal. calcd for C22H18ClF4N3O4: C 52.86, H 3.63,
N 8.41; found C 52.80, H 3.67, N 8.30.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydropyrimidin-1(6H)-yl)phenyl)-2-(4-
nitrophenoxy)acetamide (4l) White solid, yield 75%,
m.p. 199.3—199.8 ℃ [V(petroleum ether)∶V(ethyl
acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ: 8.59 (s,
1H, NH), 8.38—8.42 (m, 1H, ArH) , 8.30—8.27 (m, 2H,
ArH), 6.79—6.29 (m, 4H, ArH), 6.37 (s, 1H, ＝CH),
4.72 (s, 2H, CH2), 3.54 (s, 3H, NCH3); IR (KBr) ν: 1727,
2-(2,4-Dichlorophenoxy)-N-(2-fluoro-5-(3-methyl-
2,6-dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-
1(6H)-yl)phenyl)acetamide (4h) Yellow solid, yield
78%, m.p. 185.1—186.3 ℃ [V(petroleum ether)∶
V(ethyl acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ:
9.01 (s, 1H, NH), 8.43 (q, J＝3.0 Hz, 1H, ArH), 7.46 (d,
J＝2.4 Hz, 1H, ArH), 7.25—7.29 (m, 1H, ArH), 7.24 (d,
J＝2.7 Hz, 1H, ArH), 6.86—6.99 (m, 1H, ArH), 6.87 (d,
J＝9.0 Hz, 1H, ArH), 6.36 (s, 1H, ＝CH), 4.63 (s, 2H,
CH2), 3.54 (s, 3H, NCH3); IR (KBr) ν: 1733, 1681 (C＝
－1
3413 (C＝O), 3413 (N—H)＋cm ; LC-MS (positive ion)
m/z (%): 483 [(M ＋ 1) , 100]. Anal. calcd for
C20H14F4N4O6: C 49.80, H 2.93, N 11.62; found C 42.97,
H 2.89, N 11.71.
－1
O), 3391 (N—H) cm ; LC-MS (positive ion) m/z (%):
2-(5-Fluoro-2,4-dinitrophenoxy)-N-(2-fluoro-5-(3-
methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-
pyrimidin-1(6H)-yl)phenyl)propanamide (4m) Yel-
506 [(M＋1)＋, 100]. Anal. calcd for C21H15Cl2F4N3O4: C
44.48, H 2.91, N 8.08; found C 44.51, H 2.89, N 8.01.
N-(2-Fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoro-
methyl)-2,3-dihydropyrimidin-1(6H)-yl)phenyl)-2-(4-
low solid, yield 74%, m.p. 202.7 — 203.7
℃
1
[V(petroleum ether)∶V(ethyl acetate)＝5∶1]; H NMR
(CDCl3, 300 MHz) δ: 9.03 (s, 1H, NH), 8.95 (d, J＝7.8
Hz, 1H, ArH), 8.35 (s, 1H, ArH), 7.26 (d, J＝5.7 Hz, 1H,
ArH), 6.96—7.04 (m, 2H, ArH), 6.36 (s, 1H, ＝CH),
5.10 (q, J＝4.5 Hz, 1H, CH), 3.55 (s, 3H, NCH3), 1.79 (d,
J＝6.6 Hz, 3H, CHCH3); IR (KBr) ν: 1731, 1696 (C＝O),
(methylthio)phenoxy)propanamide (4i)
Yellow
solid, yield 82%, 38.8—40.9 ℃ [V(petroleum ether)∶
V(ethyl acetate)＝5∶1]; 1H NMR (CDCl3, 300 MHz) δ:
9.01 (s, 1H, NH), 8.44 (q, J＝1.5 Hz, 1H, ArH), 7.19—
7.26 (m, 1H, ArH), 6.70—7.06 (m, 5H, ArH), 6.36 (s,
1H, ＝CH), 4.66 (q, J＝9.0 Hz, 1H, CH), 3.87 (s, 3H,
SCH3), 3.57 (s, 3H, NCH3), 1.63 (d, J＝6.9 Hz, 3H,
CHCH3); IR (KBr) ν: 1732, 1687 (C＝O), 3357 (N—H)
－1
3387 (N＋—H) cm ; LC-MS (positive ion) m/z (%): 560
[(M＋1) , 100]. Anal. calcd for C21H14F5N5O8: C 45.09,
H 2.52, N 12.59; found C 44.93, H 2.46, N 12.65.
＋
－1
cm ; LC-MS (positive ion) m/z (%): 498 [(M＋1) ,
100]. Anal. calcd for C22H19F4N3O4S: C 53.12, H 3.85,
N 8.45; found C 53.07, H 3.95, N 8.52.
Syntheses of target compounds
The starting material 4-fluoroaniline (5) was treated
with methyl chloroformate to give ethyl 4-fluorophenyl-
carbamate (6), which was followed by incorporation
with ethyl 3-amino-4,4,4-trifluorobut-2-enoate to pro-
vide 3-(4-fluorophenyl)-6-(trifluoromethyl)pyrimidine-
2,4-(1H,3H)-dione (7). Compound 7 and iodomethane
were treated with potassium carbonate in DMF to yield
3-(4-fluorophenyl)-1-methyl-6-(trifluorometheyl)py-
rimidine-2,4(1H,3H)-dione (8), which was followed by
nitration reaction using the mixture of HNO3 and H2SO4
to form 3-(4-fluorophenyl-3-nitrophenyl)-1-methyl-6-
(trifluoromethyl)pyrimidine-2,4(1H,3H)-dione (9). Hy-
drogenation reaction of compound 9 using iron powders
as reducing reagent formed 3-(3-amino-4-fluoro-
phenyl)-1-methyl-6-(trifluoromethyl)pyrimidine-
2,4(1H,3H)-dione (10). The detail synthesis processes
for intermediates 6—10 were modified on the basis of
the literature.14 Their melting points were listed as fol-
2-(2-Fluoro-4-nitrophenoxy)-N-(2-fluoro-5-(3-
methyl-2,6-dioxo-4-(trifluoromethyl)-2,3-dihydro-
pyrimidin-1(6H)-yl)phenyl)propanamide (4j) Yel-
low solid, yield 81%, m.p. 166.8 — 167.1
℃
[V(petroleum ether)∶V(ethyl acetate)＝5∶1]; 1H NMR
(CDCl3, 300 MHz) δ: 9.13 (s, 1H, NH), 8.38 (q, J＝3.0
Hz, 1H, ArH), 7.74—7.78 (m, 1H, ArH), 7.33—7.37 (m,
1H, ArH), 7.21—7.25 (m, 1H, ArH); 7.07—7.11 (m, 1H,
ArH), 6.93—6.99 (m, 1H, ArH), 6.36 (s, 1H, ＝CH),
4.99 (q, J＝5.3 Hz, 1H, CH), 3.53 (s, 3H, NCH3), 1.71
(d, J＝6.6 Hz, 3H, CHCH3); IR (KBr) ν: 1728, 1687
－1
(C＝O), 3372 (N—H) cm ; LC-MS (positive ion) m/z
(%): 515 [(M＋1)＋, 100]. Anal. calcd for C21H15F5N4O6:
C 49.04, H 2.94, N 10.89; found C 48.96, H 2.98, N
10.93.
2-(Biphenyl-4-yloxy)-N-(2-fluoro-5-(3-methyl-2,6-
dioxo-4-(trifluoromethyl)-2,3-dihydropyrimidin-
2404
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Chin. J. Chem. 2011, 29, 2401— 2406

Synthesis and Herbicidal Activity of Novel Derivatives
lows: 6, m.p. 54.8—56.0 ℃; 8, m.p. 129.1—129.9 ℃;
9, m.p. 168.9—170.0 ℃; 10, m.p. 165.9—167.6 ℃.
Reaction of intermediate 10 with an appropriate
2-phenoxypropanoyl chloride or 2-phenoxyacetyl chlo-
ride in the presence of triethylamine results in the target
compounds 4.
a depth of 6 cm. Approximately 20 seeds of A.
theophrasti, C. album, A. ascendens, D. sanguinalis, E.
crus-galli, and S. viridis were sown in the soil at the
depth of 5-mm and grown at 22—25 ℃ in a green-
house. The diluted formulation test solutions were ap-
plied to pre-emergence for 24 h after weeds were sown.
For the post-emergence treatment, dicotyledonous
weeds were treated at the 2-leaf stage and monocotyle-
donous weeds were treated at the 1-leaf stage. The pre-
and post-emergence application rates were 75 g of ai/ha.
Untreated seedlings were used as the control group
while the solvent (N,N-dimethylformamide)-treated
seedlings were used as the solvent control group. Each
treatment was conducted in triplicate. After cultivation
for 15 d, the herbicidal activities on test weeds were
evaluated by comparing visually the weed growth inhi-
bition of all test treatments with untreated controls, cal-
culated as the average of the triplicates, and rated on the
basis of percentage of weed growth inhibition using the
following rating system: good (＋＋), ＞80%; fair (＋),
50%—80%; poor (－), ＜50%.
The as-synthesized compounds 4 were characterized
1
by IR, H NMR, mass spectra and elemental analyses.
All spectra and data were consistent with the assigned
structures. The IR spectra of compounds showed N—H
－1
and C＝O stretching bands at ca. 3412 and 1700 cm ,
respectively.
General procedure for the biological activity of the
4a— 4m
Test compounds were formulated as 100 g/L emulsi-
fied concentrates by using N,N-dimethylform-
amide as solvent and TW-80 as emulsification reagent.
The stock solutions were diluted with water to the re-
quired concentration and applied to pot-grown plants in
a greenhouse. The soil used was a clay soil with pH of
6.5, 1.7% of organic matter, 37.5% of clay particles, and
CEC of 12.9 cmol/kg. The rate of application (grams of
active ingredient (ai) per hectare) was calculated by the
total amount of active ingredient in the formulation di-
vided by the surface area of the pot.
Result and discussion
Herbicidal activity
As shown in Table 1, most of the as-prepared com-
pounds have good herbicidal activities against dicoty
ledonous weeds tested at the dosage of 75 g ai/ha.
Among the all tested compounds, compounds 4a—4i
showed good herbicidal activities at both pre-emergence
Determination of herbicidal activity against dicoty-
ledonous weeds and monocotyledonous weeds
Plastic pots (9-cm diameter) were filled with soil to
Table 1 Comparison among synthesized chemicals on the weed control activity
Pre-emergence activity (75 g ai/ha)
Post-emergence activity (75 g ai/ha)
CA AA
No X
Y
ATa
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋
CA
AA
DS
－
－
－
－
－
－
－
－
－
－
－
－
－
EC
－
－
－
－
－
－
－
－
－
－
－
－
－
SV
－
－
－
－
－
－
－
－
－
－
－
－
－
AT
DS
－
＋＋
－
－
－
－
－
－
－
－
－
－
－
EC
－
＋
－
－
－
－
－
－
－
－
－
－
－
SV
－
＋＋
－
－
－
－
－
－
－
－
－
－
－
b
4a CH3 2-Cl, 4-Cl
4b CH3 2-OCH3
4c CH3 3-CH3
4d CH3 4-CH3
4e CH3 3-F
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
＋
＋＋
＋＋
＋＋
＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋ ＋＋
＋＋
＋＋
＋＋
＋＋
＋＋
－
4f CH3
4g CH3 3-CH3, 4-Cl
4h 2-Cl, 4-Cl
4i CH3 4-SCH3
4j 2-F, 4-NO2,
4k CH3 4-Ph
4l 4-NO2
4m CH3 5-F, 2-NO2, 4-NO2
H
H
＋
H
＋＋
－
＋
－
－
－
＋
＋
＋＋
H
－
－
－
－
－
－
－
－
－
－
a AT for Abutilon theophrasti Medic; CA for Chenopodium album L.; AA for Amaranthus ascendens L.; DS for Digitaria sanguinalis L.;
EC for Echinochloa crus-galli L.; SV for Setaria viridis L. b Rating system for the growth inhibition percentage: ＋＋ for＞80%; ＋ for
50%—80%; － for ＜50%.
Chin. J. Chem. 2011, 29, 2401— 2406
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2405

Wu et al.
FULL PAPER
and post-emergence treatment against two or three kinds
of dicotyledonous weeds, such as Abutilon theophrasti
Medic, A. ascendens, and C. album. Compound 4j ex-
hibits almost the same activities at pre-emergence
treatments against three kinds of dicotyledonous weeds.
Compound 4k has close herbicidal activities at both
pre-emergence and post-emergence treatments against
three kinds of dicotyledonous weeds. But compounds 4l
and 4m have poor activities at the conditions tested, at
either pre- or post-emergency. Furthermore, all test
compounds, except compound 4b, showed lower or no
herbicidal activities at both pre-emergence and at
post-emergence treatments against monocotyledon
weeds D. sanguinalis, E. crus-galli, and S. viridis. The
result is demonstrated that the combination of the active
moieties between 4-trifluoromethyluracil and phenoxy
carboxylic acid has continually held their activities
against dicotyledonous weeds, but has not good herbi-
cidal efficacy against monocotyledon weeds. The test
data indicate that we did not get the new compounds
with brand spectrum herbicidal activity on dicotyledo-
nous weeds and monocotyledon weeds.
example, compound 4j (Y＝2-F, 4-NO2) exhibits better
herbicidal activities than 4l (Y＝4-NO2).
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Structure-activity relationship study
Some interesting structure-activity relationship still
can be drawn from the data in Table 1. Firstly, the opti-
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activities. Thirdly, it is also not obvious whether intro-
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the herbicidal activities of corresponding compounds.
The activities between 4a (X＝CH3) and 4h (X＝H)
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fluorine atom on herbicidal activities is obvious. The
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 2401— 2406