Design, Synthesis, and Herbicidal Evaluation of Novel Uracil Derivatives Containing 1,3,4-Thiadiazolyl Moiety

Article abstract of DOI:10.1002/jhet.2160

Uracil derivatives, such as commercial herbicides butafenacil and benzfendizone, have been identified as inhibitors of protoporphyrinogen oxidase (Protox, EC 1.3.3.4), one of the most important action targets of herbicides. In order to search for novel Pr

Full text of DOI:10.1002/jhet.2160

Month 2014 Design, Synthesis, and Herbicidal Evaluation of Novel Uracil Derivatives
Containing 1,3,4-Thiadiazolyl Moiety
*
Lei-En He, Ying-Ying Wu, Han-Yun Zhang, Man-Yun Liu, and De-Qing Shi
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal
University, Wuhan 430079, Hubei, People’s Republic of China
*
E-mail: chshidq@mail.ccnu.edu.cn
Received October 12, 2013
DOI 10.1002/jhet.2160
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
Y
X
Y
X
O
O
S
S
R
NEt3/CH3CN
R
+
N
COCl
H2N
N
CONH
N
N
N
N
N
O
N
O
F3C
F3C
CH3
CH3
8a-8n
7
6
Uracil derivatives, such as commercial herbicides butafenacil and benzfendizone, have been identified as
inhibitors of protoporphyrinogen oxidase (Protox, EC 1.3.3.4), one of the most important action targets of
herbicides. In order to search for novel Protox inhibitors with high efficacy, broad-spectrum activity, and
safety to crops, commercially herbicide butafenacil was used as lead compound for further optimization; a
series of title compounds 8a ~ 8n were designed and synthesized by introducing 1,3,4-thiadiazole moiety
into the uracil skeleton. The preliminary bioassays (in vitro) indicated that most of the target compounds
displayed better inhibition against Echinochloa crus-galli than Brassica campestris. The greenhouse
bioassay results indicated that most of the compounds tested exhibited good-to-excellent herbicidal activities
against B. campestris, A. retroflexus, E. crusgalli, and D. sanguinalis in pre-emergence treatment at a
dose of 1500 g/ha, for example, compound 8d showed 100% inhibition against the four plants tested in
pre-emergence treatment at a dose of 1500 g/ha. So, these types of skeletons can be used as valuable lead
compounds for the development of a pre-emergent herbicide.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
as valuable lead compounds for further optimization for
developing of a pre-emergent herbicide.
The protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4), an
enzyme in the chlorophyll and heme biosynthetic pathway,
is the target of many classes of herbicides such as diphenyl
ether, cyclic imides, triazolinones, tetrazolinones, benzoxa-
zinones, oxadiazolones, uracils, and thiadiazolidines.[1–4]
To date, several uracil derivatives have been commercialized
(Fig. 1); among them, for example, bromacil and isocil were
firstly developed as a commercial herbicides by DuPont Corp.
in the 1962.[5] Butafenacil, benzfendizone, and saflufenacil
were subsequently commercialized by Syngenta, FMC, and
BASF corporations, respectively.[6–8] These high-active
uracil-type herbicides possess the following structural fea-
tures: (i) a central 1H-pyrimidine-2,4-dione moiety; (ii) a
methyl group linking at N-1 position, and trifluoromethyl
at C-6 and substituted phenyl at N-3 position of uracil;
(iii) the phenyl at N-3, when Cl or F introduced into the
C-2, or/and C-4, and an ester or amide moiety into the C-
5 position of the benzene ring, the compounds always
displayed good herbicidal activities. 1,3,4-Thiadiazole
derivatives usually display pharmacological and agro-
chemical activities.[9–15] Compounds 8 were designed
and synthesized by introducing 1,3,4-thiadiazole moieties
from the meta to the benzene at N-3 position of uracil
skeleton, as shown in Scheme 1. Herein, we report the
detailed synthesis and herbicidal activities of compounds
8, and the results indicated that the target compounds
displayed good herbicidal activity. So they can be used
RESULTS AND DISCUSSION
The target compounds 8a ~ 8n were synthesized via
multi-step procedure as shown in Scheme 1. 2-Amino-5-
substituted-1,3,4-thiadiazoles 7 were synthesized by refer-
ring to the known procedure.[16] The key intermediates,
2,4-disubstituted-3-[3-methyl-2,6-dioxo-4-trifluoromethyl-
3,6-dihydropyrimidin-1(2H)-yl]-benzoic acids 5, were
achieved according to the reported methods.[17,18] First,
ethyl phenyl-carbamate 1 underwent annulation with ethyl
3-amino-4,4,4-trifluoro-but-2-enoate 2 to yield ethyl 2,4-
disubstituted-5-(2,6-dioxo-4-trifluoromethyl-3,6-dihydro-
2H-pyrimidin-1-yl)-benzoate 3 in the presence of NaH/
DMF, the subsequent N-methylation and hydrolysis yielded
5 in moderate yields. Second, intermediates 5 reacted with
oxalyl chloride in the refluxing CHCl3 solution, followed by
nucleophilic substitution with 2-amino-5-substituted-1,3,4-
thiadiazoles 7 to give target compounds 8 in 63–94% yields.
All intermediates were determined by proton nuclear
magnetic resonance (1H NMR), and all new target com-
1
pounds were characterized with H NMR, infrared (IR)
spectrum, electron ionization mass spectrometry (EI-MS),
and elemental analysis. The IR spectrum of title com-
pounds 8a ~ 8n showed absorption band at 3430 and
2960 cmÀ1 for N-H and C-H stretching, respectively. The
© 2014 HeteroCorporation

L.-E. He, Y.-Y. Wu, H.-Y. Zhang, M.-Y. Liu, and D.-Q. Shi
Vol 000
O
O
O
Cl
Br
Br
N
N
N
N
H
O
N
H
O
H C
3
N
H
O
H C
H C
3
3
tertbacil
C H
isocil
bromacil
2
5
F
Cl
O
O
Cl
COO
O
O
N
H
O
N
N
N
O
O
O
O
N
S
N
N
O
O
N
O
F C
O
H CO
3
3
F C
3
O
F C
3
CH
3
CH
3
CH
3
butafenacil
benzfendizone
saflufenacil
Figure 1. Structures of some commercial uracil Protox inhibitors.
characteristic stretching vibrations ν (C = O) and ν (C = N)
are around at ca 1730 cmÀ1 and ca 1285 cmÀ1, respec-
tively. In the H NMR spectra of the title compounds, the
100 mg/L. For example, compounds 8b, 8d, and 8j pos-
sessed 85.3%, 88.2%, and 93.3% inhibitory activities against
E. crus-galli at 100 mg/L, respectively. Moreover, com-
pounds 8b, 8d, and 8j possessed 67.6%, 67.6%, and 67.6%
inhibitory activities against E. crus-galli at 10mg/L, respec-
tively. However, compounds 8 didn’t exhibit good inhibitory
activities against B. campestris L. at 100 mg/L and 10 mg/L.
In order to evaluate further their herbicidal activities, the
greenhouse bioassays were evaluated for most of the target
compounds according to the known method, [20] which is
listed in Table 2. The results indicated that most of the com-
pounds tested good-to-excellent herbicidal activity against B.
campestris, A. retroflexus, E. crus-galli, and D. sanguinalis
in pre-emergence treatment at a dose of 1500g/ha. As shown
in Table 2, all the compounds tested showed excellent
inhibitory activities against B. campestris in pre-emergence
treatment at a dose of 1500 g/ha; second, compounds 8b,
1
N-H proton was observed at δ 10.0–12.5 ppm, and the aro-
matic protons signals were observed at δ 8.5–6.5 ppm. The
three protons of methyl attached the uracil exhibited as sin-
glet at δ ca 3.6 ppm, respectively. The EI-MS of the title
compounds 8 showed molecular ion peak and anticipated
fragmentation ion peaks clearly.
The preliminary herbicidal activity (in vitro) of the title
compounds 8 against Brassica campestris L. (rape) and
Echinochloa crus-galli (barnyard grass) has been investi-
gated according to the reported method [19] at the concen-
trations of 100 mg/L and 10 mg/L, which is summarized in
Table 1. The results indicated that some of the title
compounds 8 possessed excellent and selective herbicidal
activities against E. crus-galli at the concentration of
Scheme 1. Synthetic route of the uracil derivatives containing 1,3,4-thiadiazole moiety 8.
Y
X
F C
3
COOC H
2
5
O
Y
Y
ClCOOC H
2
5
2
N
COOC H
2
H N
2
5
H N
2
X
C H OOCHN
X
2
5
Pyridine
N
H
O
NaH
F C
3
CO C H
CO C H
2 2 5
2
2
5
3
1
Y
X
Y
N
X
Y
N
X
O
O
N
O
ClCOCOCl
(1) NaOH
N
COCl
CO C H
COOH
CH I
3
2
2
5
CH Cl
2
2
(2) H O
3
N
O
O
R
N
O
F C
3
F C
F C
3
3
CH
CH
CH
3
3
3
6
5
4
Y
N
X
S
O
N
H N
2
S
R
7
N
N
CONH
N
N
O
NEt /CH CN
3
3
F C
3
CH
3
8a-8n
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Novel Uracil Derivatives Containing 1,3,4-Thiadiazolyl Moiety
Table 1
Herbicidal activities of the target compounds 8 (in vitro, percent inhibition, %).
In conclusion, two series of novel uracil derivatives
8 containing a 1,3,4-thiadiazole moiety were designed
and synthesized by the multistep reactions. Their structures
were clearly confirmed by spectroscopy data (IR, 1H NMR,
and MS) and elemental analysis. The bioassays indicated
that some of the target compounds displayed good-to-
excellent herbicidal activity against B. campestris, A.
retroflexus, E. crus-galli, and D. sanguinalis in pre-
emergence treatment at a dose of 1500 g/ha. So, these types
of skeletons can be used as valuable lead compounds for
the development of a pre-emergent herbicide.
B. campestris root test
E. crusgalli cup test
Compound
10 mg/L
100 mg/L
10 mg/L
100 mg/L
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
0
0
0
16.4
0
0
0
0
0
37.0
6.9
18.8
0
20.0
25.1
15.4
67.2
34.9
37.7
9.8
4.7
0
64.1
7.5
43.6
0
32.4
67.6
14.7
67.6
26.5
47.0
5.9
61.8
17.6
67.6
5.9
52.9
85.3
79.4
88.2
76.5
79.4
26.5
76.5
35.3
91.2
33.8
57.4
2.9
EXPERIMENTAL
Reagents were all analytically pure. All solvents were dried by
standard methods in advance and distilled before use. Melting
points were measured on a WRS-1B digital melting point apparatus
55.9
0
11.8
0
17.4
17.6
1
and were uncorrected. H NMR was recorded on a Mercury-plus
400 (400MHz) or Varian Mercury-plus 600 (600 MHz) in CDCl3
solution with tetramethylsilane as the internal standard, and chemi-
cal-shift values (δ) were given in parts per million. IR spectra were
recorded on a Nicolet AVATAR360 spectrometer as KBr tablets.
The MS were measured on a Finnigan TRACE spectrometer.
Elemental analysis was performed on a Vario EL III Element
Analyzer. Flash chromatography was carried out with Merck silica
gel (230–400 Mesh). 2-Amino-5-substituted-1,3,4-thiadiazoles 7
were prepared according to the reported method (16).
8d, 8f, and 8j possessed excellent inhibitory activities against
A. retroflexus in pre-emergence treatment; and compounds
8b, 8d, and 8e possessed excellent inhibitory activities
against E. crus-galli in pre-emergence treatment; 8b, 8d,
and 8f possessed excellent inhibitory activities against D.
sanguinalis in pre-emergence treatment. However, most of
compounds 8 tested didn’t exhibit good inhibitory activities
against E. crus-galli and D. sanguinalis in post-emergence
treatment. As for the preliminary structure-activity relation-
ships, comparing activity among compounds 8b~ 8j in
Table 2, compounds 8b, 8d, and 8f with fluorine as X
exhibited the good herbicidal activity irrespective of the
different R group (H, methyl or ethyl) linking with the
1,3,4-thiadiazole.
Synthesis of 2,4-disubstituted-3-[3-methyl-2,6-dioxo-4-trifluo-
romethyl-3,6-dihydropyrimidin-1(2H)-yl]-benzoic acid 5.
5 were synthesized according to the related literatures (17, 18)
Data for 5a. (X = H, Y = H). White solid; yield, 75%; m.p.,
241.5–243.4 °C. 1H NMR (400 MHz, CDCl3) δ: 8.20
(d, J = 7.6 Hz, 1H), 7.98 (s, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.48
(d, J = 8.0 Hz, 1H), 6.41 (s, 1H), 3.58 (s, 3H, CH3). Anal. calcd
for C13H9F3N2O4: C, 49.69; H, 2.89; N, 8.92. Found: C, 49.81;
H, 2.83; N, 8.78.
Data for 5b. (X = F, Y = H). White solid; yield, 68%; m.p.,
218.5–220.0 °C. 1H NMR (400 MHz, CDCl3) δ: 7.92
(d, J = 3.6 Hz, 1H), 7.43 (s, 1H), 7.66 (t, J = 8.8 Hz, 1H), 6.40
(s, 1H), 3.57 (s, 3H, CH3). Anal. calcd for C13H8F4N2O4: C,
47.00; H, 2.43; N, 8.43. Found: C, 46.87; H, 2.59; N, 8.51.
In addition, compound 8d showed 100% inhibition
against the four plants tested in pre-emergence treatment
at a dose of 1500 g/ha. So, these types of skeletons can
be used as valuable lead compounds for the development
of a pre-emergent herbicide.
Table 2
Herbicidal activity of some of target compounds 8 in greenhouse (1.5 kg/ha, percent inhibition, %).
Pre-emergence treatment
Post-emergence treatment
D.
Compound
B. campestris A. retroflexus
E. crusgalli D. sanguinalis B. campestris A. retroflexus E. crus-galli
sanguinalis
8b
8c
8d
8e
8f
8 h
8j
100
99.0
100
61.7
100
89.6
100
73.8
95.0
100
92.8
0
100
100
86.2
16.8
64.6
99.5
100
57.1
100
29.7
94.9
10.0
61.4
70.0
0
100
0
100
85
96.0
28.3
97.0
17.8
71.8
57.0
31.2
25.3
5.0
21.9
16.3
15.2
8.0
41.4
20.0
35.6
0
20.0
15.0
10.0
100
100
100
100
100
100
100
50.0
100
10.0
100
Flumioxazin
100
100
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

L.-E. He, Y.-Y. Wu, H.-Y. Zhang, M.-Y. Liu, and D.-Q. Shi
Vol 000
Data for 5c. (X = H, Y = F). White solid; yield, 65%; m.p.,
174.9–176.0 °C. 1H NMR (400 MHz, CDCl3) δ: 8.23 (s, 1H),
8.06 (d, J = 6.0 Hz, 1H), 7.34 (t, J = 8.8 Hz, 1H), 6.40 (s, 1H),
3.58 (s, 3H, CH3). Anal. calcd for C13H8F4N2O4: C, 47.00; H,
2.43; N, 8.43. Found: C, 47.15; H, 2.52; N, 8.47.
General procedure for the synthesis of target compounds
8. Three millimol amount of 5, a drop of dimethylformamide
and oxalyl chloride (9 mmol) in anhydrous chloroform (20 mL)
were stirred at room temperature for 2 h. The reaction was
stirred at 50 °C for 5–8 h. After the solvent was evaporated
under vacuum, the crude product 6 was obtained as yellow
solid, which can be used for the next step without further
purification.
Data for 8e. (X = H, Y = H, R = C2H5). White solid; yield,
83%; m.p., 263.0–264.6 °C. IR (KBr, cmÀ1) 3428, 3184, 2973,
1731, 1676, 1538, 1485, 1377, 1308, 1286, 1185, 1139, 1068,
1046; 1H NMR (600 MHz, CDCl3) δ: 12.05 (s, NH), 8.30 (d,
J = 7.8 Hz, 1H), 8.08 (s, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.46 (d,
J = 7.8 Hz, 1H), 6.40 (s, 1H), 3.57 (s, 3H, CH3), 3.05
(q, J = 7.8 Hz, 2H, CH2), 1.42 (t, J = 7.2 Hz, 3H, CH3); EI-MS:
m/z (%) 425 (M+, 3.4), 424 (6.9), 371 (6.7), 370 (34.9), 298
(15.7), 297 (100), 232 (16.5), 219 (6.5), 156 (6.8), 147 (8.1),
146 (97.6), 118 (18.5), 90 (15.2), 82 (7.8). Anal. calcd for
C17H14F3N5O3S: C, 48.00; H, 3.32; N, 16.46. Found: C, 48.14;
H, 3.13; N, 16.30.
Data for 8f.
(X = F, Y = H, R = C2H5). White solid; yield,
Three millimol amount of 7, pyridine (4.5 mmol) and anhy-
drous CH3CN (20 mL) was added to a 50 mL three-necked flask,
the mixture was cooled at 0–5 °C, the solution of 6 (3 mmol) in
anhydrous CH3CN (5 mL) was added dropwise slowly, and the
resultant mixture was stirred for 5–8 h at ambient temperature till
the reaction finished (monitored by thin layer chromatography).
The work-up involved stripping of the most of solvent followed
by an addition of water (20 mL) and extraction of the product
mixture into ethyl acetate, washing with NaHCO3, dilute HCl
and water, respectively, drying over Na2SO4, filtration. After the
solvent was evaporated under vacuum, the crude product was pu-
rified through a silica gel column eluted with petroleum ether/
ethyl acetate (3:1, v/v) to give the corresponding pure title com-
pounds 8 as white solid.
68%; m.p., 223.2–225.0 °C. IR (KBr, cmÀ1) 3441, 2975, 1727,
1672, 1534, 1481, 1376, 1302, 1283, 1188, 1072, 1042; 1H
NMR (600 MHz, CDCl3) δ: 10.15 (s, NH), 8.07 (dd, J = 6.6 Hz,
J = 3.0 Hz, 1H), 7.48 (dd, J = 3.6 Hz, J = 7.2 Hz, 1H), 7.39 (t,
J = 8.4 Hz, 1H), 6.39 (s, 1H), 3.57 (s, 3H, CH3), 3.10 (q,
J = 7.8 Hz, 2H, CH2), 1.44 (t, J = 7.8 Hz, 3H, CH3). Anal. calcd
for C17H13F4N5O3S: C, 46.05; H, 2.96; N, 15.80. Found: C,
46.17; H, 2.70; N, 15.94.
Data for 8g.
(X = H, Y = H, R = i-Pr). White solid; yield,
89%; m.p., 267.8–269.3 °C. IR (KBr, cmÀ1) 3426, 3137, 2964,
1730, 1688, 1536, 1481, 1376, 1318, 1278, 1145, 1045, 739;
1H NMR (600 MHz, CDCl3) δ: 12.10 (s, NH), 8.37
(d, J = 7.2 Hz, 1H), 8.06 (s, 1H), 7.64 (t, J = 8.4 Hz, 1H), 7.45
(d, J = 7.8 Hz, 1H), 6.40 (s, 1H), 3.57 (s, 3H, CH3), 3.35–3.37
(m, 1H, CH), 1.44 (d, J = 6.6 Hz, 6H, CH3); EI-MS: m/z (%)
439 (M+, 5.2), 438 (4.9), 371 (7.4), 370 (34.6), 343 (9.4), 341
(7.1), 298 (13.7), 297 (100), 261 (8.2), 246 (24.5), 219 (8.7),
171 (8.4), 170 (12.5), 162 (11.3), 147 (10.2), 146 (98.0), 118
(20.2), 90 (19.6), 77 (16.0). Anal. calcd for C18H16F3N5O3S: C,
49.20; H, 3.67; N, 15.94. Found: C, 49.05; H, 3.72; N, 16.06.
Data for 8a. (X = H, Y = H, R = H). White solid; yield, 75%;
m.p., >270 °C. IR (KBr, cmÀ1) 3430, 3075, 1728, 1681, 1544,
1
1487, 1375, 1303, 1180, 1140; H NMR (600 MHz, CDCl3) δ:
8.75 (s, 1H), 8.26 (d, J = 7.8 Hz, 1H), 8.20 (s, 1H), 7.68 (t,
J = 7.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 6.42 (s, 1H), 3.57 (s,
3H, CH3). Anal. calcd for C15H10F3N5O3S: C, 45.34; H, 2.54;
N, 17.63. Found: C, 45.20; H, 2.62; N, 17.77.
Data for 8h.
(X = F, Y = H, R = i-Pr). White solid; yield,
92%; m.p., 242.7–244.2 °C. IR (KBr, cmÀ1) 3424, 2962, 1726,
1687, 1532, 1477, 1372, 1310, 1276, 1148, 1048, 742; 1H
NMR (600 MHz, CDCl3) δ: 10.17 (s, NH), 8.06 (dd,
J = 2.4 Hz, J = 6.6 Hz, 1H), 7.47 (t, J = 4.2 Hz, 1H), 7.38 (t,
J = 10.2 Hz, 1H), 6.39 (s, 1H), 3.56 (s, 3H, CH3), 3.40–3.45
(m, 1H, CH), 1.45 (d, J = 6.6 Hz, 6H, CH3). Anal. calcd for
C18H15F4N5O3S: C, 47.27; H, 3.31; N, 15.31. Found: C,
47.42; H, 3.25; N, 15.20.
Data for 8b. (X = F, Y = H, R = H). White solid; yield, 82%;
m.p., 140.8–142.3 °C. IR (KBr, cmÀ1) 3435, 3170, 2955, 1731,
1682, 1538, 1498, 1374, 1264, 1186, 1161, 1047; 1H NMR
(600 MHz, CDCl3) δ: 10.63 (s, NH), 8.87 (s, 1H), 8.09 (d,
J = 4.2 Hz, 1H), 7.49 (t, J = 4.2 Hz, 1H), 7.39 (t, J = 9.6 Hz, 1H),
6.40 (s, 1H), 3.57 (s, 3H, CH3); EI-MS: m/z (%) 415 (M+, 3.0),
396 (9.1), 389 (9.7), 388 (27.4), 315 (65.9), 222 (12.7), 165
(9.0), 164 (100), 129 (9.5), 108 (15). Anal. calcd for
C15H9F4N5O3S: C, 43.38; H, 2.18; N, 16.86. Found: C, 43.11;
H, 2.13; N, 16.98.
Data for 8i.
(X = H, Y = H, R = n-Pr). White solid; yield,
88%; mp 241.3–242.7 °C. IR (KBr, cmÀ1) 3424, 3132, 2958,
1736, 1687, 1538, 1478, 1374, 1315, 1276, 1142, 1043, 736;
1H NMR (600 MHz, CDCl3) δ: 12.05 (s, NH), 8.32
(d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.45
(d, J = 7.8 Hz, 1H), 6.40 (s, 1H), 3.57 (s, 3H, CH3), 2.98
(t, J = 7.2 Hz, 2H, CH2), 1.82–1.86 (m, 2H, CH2), 1.05
(t, J = 7.2 Hz, 3H, CH3). Anal. calcd for C18H16F3N5O3S: C,
49.20; H, 3.67; N, 15.94. Found: C, 49.37; H, 3.71; N, 15.83.
Data for 8c.
(X = H, Y = H, R = CH3). White solid; yield,
81%; m.p., 256.0–258.0 °C. IR (KBr, cmÀ1) 3431, 3230, 1726,
1
1682, 1545, 1485, 1378, 1308, 1183, 1142, 836, 706; H NMR
(400 MHz, CDCl3) δ: 11.95 (s, NH), 8.27 (d, J = 8.0 Hz, 1H),
8.11 (s, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 7.2 Hz, 1H),
6.54 (s, 1H), 3.57 (s, 3H, CH3), 2.68 (s, 3H, CH3); EI-MS: m/z
(%) 411 (M+, 4.2), 371 (5.4), 370 (32.5), 315 (5.0), 298 (13.5),
297 (88.1), 218 (21.2), 146 (100), 118 (21.0), 90 (11.2). Anal.
calcd for C16H12F3N5O3S: C, 46.72; H, 2.94; N, 17.02. Found:
C, 46.93; H, 2.85; N, 16.87.
Data for 8j.
(X = F, Y = H, R = n-Pr). White solid; yield,
94%; m.p., 185.2–186.9 °C. IR (KBr, cmÀ1) 3311, 2966, 1728,
1
1677, 1534, 1487, 1380, 1261, 1186, 1141, 1046, 836, 757; H
Data for 8d.
(X = F, Y = H, R = CH3). White solid; yield,
NMR (600 MHz, CDCl3) δ: 10.25 (s, NH), 8.07 (t, J = 3.6 Hz,
1H), 7.47 (t, J = 4.8 Hz, 1H), 7.37 (t, J = 9.6 Hz, 1H), 6.39 (s,
1H), 3.56 (s, 3H, CH3), 3.04 (t, J = 7.2 Hz, 1H, CH2), 1.83–1.87
(m, 2H, CH2), 1.05 (t, J = 7.2 Hz, 3H, CH3); EI-MS: m/z (%)
457 (M+, 2.7), 438 (8.6), 430 (8.0), 429 (35.7), 316 (8.9), 315
(84.2), 264 (14.0), 164 (100), 136 (8.5), 108 (17.6), 82 (9.5).
Anal. calcd for C18H15F4N5O3S: C, 47.27; H, 3.31; N, 15.31.
Found: C, 47.06; H, 3.34; N, 15.40.
87%; m.p., 251.9–253.7 °C. IR (KBr, cmÀ1) 3435, 3226, 1724,
1686, 1541, 1486, 1375, 1310, 1184, 1138; 1H NMR
(600 MHz, CDCl3) δ: 10.08 (s, NH), 8.08 (dd, J = 6.6 Hz,
J = 2.4 Hz, 1H), 7.48 (dd, J = 3.6 Hz, J = 8.4 Hz, 1H), 7.38
(dd, J = 8.4 Hz, J = 10.8 Hz, 1H), 6.39 (s, 1H), 3.55 (s, 3H,
CH3), 2.74 (s, 3H, CH3). Anal. calcd for C16H11F4N5O3S: C,
44.76; H, 2.58; N, 16.31. Found: C, 44.59; H, 2.61; N, 16.17.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Novel Uracil Derivatives Containing 1,3,4-Thiadiazolyl Moiety
Data for 8k.
(X =H, Y = H, R = n-Bu). White solid; yield,
The cup was placed in a bright room, and the seeds were
allowed to germinate for 65 h at 28 1 °C. The heights of the
above ground parts of the seedlings in each cup were measured,
and the means were calculated. The percentage inhibition was
used to describe the control efficiency of the compounds, which
was summarized in Table 1.
Glssshouse bioassays. Culture Method. The seeds were
planted in 6 cm diameter plastic boxes containing artificial mixed
soil. Before plant emergence, the boxes were covered with plastic
film to retain moisture. Plants were grown in the green house. The
fresh weight of the above ground tissues was measured 10 days
after the treatment. The inhibition percent was used to describe the
control efficiency of the compounds.
87%; m.p., 214.9–216.4 °C. IR (KBr, cmÀ1) 3437, 2936, 1731,
1675, 1536, 1483, 1376, 1306, 1284, 1187, 1146, 1046; 1H NMR
(600 MHz, CDCl3) δ: 10.20 (s, NH), 8.33 (d, J =7.8 Hz, 1H), 8.09
(s, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.44 (d, J = 7.8 Hz, 1H), 6.40 (s,
1H), 3.56 (s, 3H, CH3), 3.01 (t, J = 7.8 Hz, 1H, CH2), 1.76–1.81
(m, 2H, CH2), 1.43–1.47 (m, 2H, CH2), 0.97 (t, J = 7.2Hz, 3H,
CH3); EI-MS: m/z (%) 453 (M+, 4.4), 412 (8.5), 411 (53.6), 370
(14.3), 298 (17.8), 297 (100), 260 (11.2), 184 (7.8), 146 (87.4),
118 (19.2), 90 (10.5), 44 (24.7). Anal. calcd for C19H18F3N5O3S:
C, 50.33; H, 4.00; N, 15.44. Found: C, 50.19; H, 4.12; N, 15.20.
Data for 8l.
(X = F, Y = H, R = n-Bu). White solid; yield,
94%; m.p., 195.8–197.5 °C. IR (KBr, cmÀ1) 3320, 2968, 1727,
1675, 1539, 1482, 1384, 1260, 1185, 1144, 1043; 1H NMR
(600 MHz, CDCl3) δ: 10.04 (s, NH), 8.08 (t, J = 4.2 Hz, 1H),
7.48 (t, J = 6.0 Hz, 1H), 7.39 (t, J = 9.6 Hz, 1H), 6.39 (s, 1H),
3.57 (s, 3H, CH3), 3.07 (t, J = 7.8 Hz, 1H, CH2), 1.78–1.83 (m,
2H, CH2), 1.43–1.49 (m, 2H, CH2), 0.97 (t, J = 7.2 Hz, 3H,
CH3). Anal. calcd for C19H17F4N5O3S: C, 48.41; H, 3.63; N,
14.86. Found: C, 48.25; H, 3.70; N, 14.69.
Treatment.
The dosage (activity ingredient) for each
compound corresponded to 1.5 kg/ha. Compounds 8 were
dissolved in 100 μL of N,N-dimethylformamide with the
addition of a little Tween 20 and then were sprayed using a
laboratory belt sprayer delivering a 750 L/ha spray volume.
Pre-emergence.
Sandy clay (100 g) in a plastic box
(11 cm × 7.5 cm × 6 cm) was wetted with water. Sprouting seeds
(15) of the weed under test were planted in fine earth (0.6 cm
depth) in the glasshouse and sprayed with the test compound
solution at 1500 g/ha.
Data for 8m.
(X = H, Y = H, R = Ph). White solid; yield,
74%; m.p., >270 °C. IR (KBr, cmÀ1) 3442, 2926, 1727, 1685,
1550, 1375, 1325, 1266, 1183, 1154, 1048, 767; 1H NMR
(400 MHz, CDCl3) δ: 13.14 (s, 1H, NH), 8.33 (d, J = 8.0 Hz,
1H), 8.12 (s, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.68 (t, J = 7.6 Hz,
1H), 7.45–7.51 (m, 4H), 6.41 (s, 1H), 3.55 (s, 3H, CH3). Anal.
calcd for C21H14F3N5O3S: C, 53.28; H, 2.98; N, 14.79. Found:
C, 53.44; H, 3.07; N, 14.91.
Postemergence.
Seedlings (one leaf and one stem) of
the weed were sprayed with the test compound solution at
1500 g/ha. For both methods, the fresh weights of the above-
ground portions were determined 24 days later, and the percent
inhibition relative to the controls was calculated. There were
two replicates for each treatment. The result was summarized in
Table 2.
Data for 8n.
(X = F, Y = H, R = Ph). White solid; yield,
73%; m.p., >270 °C. IR (KBr, cmÀ1) 3440, 2922, 1728, 1682,
1552, 1376, 1321, 1259, 1189, 1149, 1046, 763; 1H NMR
(600 MHz, CDCl3) δ: 10.35 (s, NH), 8.11 (d, J = 4.2 Hz, 1H),
7.97 (d, J = 3.6 Hz, 2H), 7.44–7.48 (m, 4H), 7.41 (t, J = 9.6 Hz,
1H), 6.39 (s, 1H), 3.57 (s, 3H, CH3); EI-MS: m/z (%) 491 (M+,
13.2), 472 (9.7), 388 (15.7), 316 (11.0), 315 (85.2), 298 (19.4),
165 (9.4), 164 (100), 136 (7.8), 108 (9.5), 92 (9.2), 44 (13.6).
Anal. calcd for C21H13F4N5O3S: C, 51.33; H, 2.67; N, 14.25.
Found: C, 51.17; H, 2.73; N, 14.35.
Acknowledgements. The authors are grateful to the National Natural
Science Foundation of China (NSFC) (grant number 21342004),
the Syngenta PhD (postgraduate) Programme, and the Open
Project of Key Laboratory of Theoretical Chemistry and
Molecular Simulation of Ministry of Education, Hunan
University of Science and Technology (No. LKF1206) for the
support of this research.
Herbicidal activity assay. In vitro bioassays.
The
herbicidal activity evaluation of the target compounds 8 were
underwent using B. campestris L. and E. crus-galli L. Beauv as
samples of annual dicotyledonous and monocotyledonous
plants, respectively. For all of the bioassay tests, there were two
replicates for each treatment.
Treatment. Compounds 8 were dissolved in 100 μL of N,N-
dimethylformamide with the addition of 2 μL of Tween 20. The
mixture of the same amount of water, N,N-dimethylformamide,
and Tween 20 was used as control.
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