Synthesis and herbicidal activity of novel 3-aminocarbonyl-2- oxazolidinethione derivatives containing a substituted pyridine ring

Article abstract of DOI:10.1021/jf051928j

A series of 3-aminocarbonyl-2-oxazolidinethione derivatives containing a substituted pyridine ring were designed and synthesized. The structures of all of the title compounds were characterized by ¹H NMR, ¹³C NMR, IR, and HRMS. Their

Full text of DOI:10.1021/jf051928j

J. Agric. Food Chem. 2006, 54, 125−129 125
Synthesis and Herbicidal Activity of Novel
3-Aminocarbonyl-2-oxazolidinethione Derivatives Containing a
Substituted Pyridine Ring
†
,†,‡
JINGNAN CUI, QINGCHUN HUANG,‡
†
GANGYUE LI, XUHONG QIAN,*
RONG ZHANG,† AND HUAI GUAN†
State Key Laboratory of Fine Chemicals, Dalian University of Technology, P.O. Box 89,
Zhongshan Road 158, Dalian 116012, Liaoning Province, People’s Republic of China, and Institute of
Pesticides and Pharmaceuticals, East China University of Science and Technology, P.O. Box 544,
Meilong Road 130, Shanghai 200237, People’s Republic of China
A series of 3-aminocarbonyl-2-oxazolidinethione derivatives containing a substituted pyridine ring
were designed and synthesized. The structures of all of the title compounds were characterized by
1H NMR, 13C NMR, IR, and HRMS. Their agricultural bioactivities were evaluated, and some of these
compounds exhibited good herbicidal activities against Echinochloa crusgalli, Sorghum vulgare,
Digitaria sanguinalis, Eclipta prostrasta, Cucumis sativus, and Brassica campestris, which were
associated mainly with their steric properties and lipophilicities based on the structure-activity
relationship discussion.
KEYWORDS: 2-Oxazolidinethiones; pyridine ring; herbicidal activity
INTRODUCTION
6), as well as low toxicity toward mammals. On the other hand,
the chemistry of 2-oxazolidinethiones has received considerable
attention because their derivatives exhibit much higher potentials
of biological activities, such as antithyroid (7, 8), antifertility
Weeds compete with crops for sunshine, water, nutrients, and
physical space and are thus capable of greatly influencing the
growth of crops and undermining both crop quality and yield.
Also, many weeds are the harbor or nest of pathogens, viruses,
and pests, which may result in the occurrence and spread of
plant diseases and insect pests in crops. Herbicides, as the main
weed control tool, play a very important role in modern
agriculture.
Since the discovery of the herbicide 2,4-dichlorophenoxy-
acetic acid (2,4-D) by Zimerman and Hitchcock, the agrochemi-
cal industry has successfully developed a wide array of
herbicides with various chemical structures and modes of action
(
(
9, 10), inhibition of dopamine â-hydroxylase (11), antibacterial
12, 13), and insecticidal activities (14). However, 2-oxazolidi-
nethione derivatives used as herbicide have been rarely reported.
This provides us with a chance to obtain the herbicidal lead
compound with 2-oxazolidinethione containing a substituted
pyridine. In this paper, we have synthesized a series of novel
compounds by introducing pyridine rings with different sub-
stituted groups into 2-oxazolidinethiones, and the results of
bioassay showed efficient herbicidal activities.
(
1). However, an inevitable problem associated with the use of
MATERIALS AND METHODS
herbicides is the occurrence of herbicide-resistant weeds (2).
For example, the widespread use of herbicides such as chlor-
sulfuron, atrazine, diclofop-methyl, and paraquat has caused
herbicide resistance in many weeds. Therefore, it is necessary
to develop efficient herbicides with novel structures and modes
of action to overcome the resistance of weeds.
In the study of pharmaceuticals and agrochemicals, the
introduction of pyridine into a parent compound may improve
the properties and biological activities of the compounds, and
many pyridyl-containing compounds are also known to possess
a wide range of biological and pharmacological activities (3-
Synthesis. Chemicals. Melting points were obtained with an X-6
micro-melting point apparatus and are uncorrected. The infrared (IR)
spectra were recorded on a Nicolet 20DXB FR-IR spectrometer using
potassium bromide pellets or films. The
on a Varian INOVA-400 spectrometer with chemical shifts reported
1
H NMR spectra were measured
1
3
as parts per million (in CDCl
NMR spectra were measured on a Varian INOVA-400 or a Bruker
AVANCE-500 spectrometer (in CDCl , TMS as internal standard).
3
, TMS as internal standard). The
C
3
Mass spectra were measured on an HP 1100 LC-MSD spectrometer.
High-resolution mass spectra (HRMS) were obtained on an HPLC-
Q-T of MS (Mcrio) spectrometer. Flash chromatography was performed
on silica gel. All of the solvents were of analytical grade. All chemicals
or reagents were purchased from standard commercial suppliers.
*
Author to whom correspondence should be addressed [telephone +86-
(
0)21-64253589; fax +86(0)21-64251386; e-mail xhqian@dlut.edu.cn or
General Procedure for the Preparation of erythro-Amino Alcohol
(1). To a solution of aminoketone (5.0 mmol) in MeOH (50 mL) was
added NaBH (25.0 mmol) in five portions every 10 min at 0 °C. After
4
xhqian@ecust.edu.cn].
†
Dalian University of Technology.
East China University of Science and Technology.
‡
1
0.1021/jf051928j CCC: $33.50
© 2006 American Chemical Society
Published on Web 12/08/2005

126 J. Agric. Food Chem., Vol. 54, No. 1, 2006
Li et al.
2
0 min of stirring, the solvent was evaporated at reduced pressure, taken
CDCl
3
) δ 1.04 (d, J ) 6.8 Hz, 3H), 1.24-1.50 (m, 8H), 1.52-1.63
up with CH
concentrated to dryness to give the crude products 1 in the range of
0-95% yields, which were directly used in the next reaction without
2
Cl
2
. The mixture was filtered, and the filtrate was
(m, 1H), 1.66-1.84 (m, 2H), 1.88-2.00 (m, 2H), 3.73-3.85 (m, 1H),
4.37 (q, J ) 7.2 Hz, 2H), 4.95-5.06 (m, 1H), 5.73 (d, J ) 8.0 Hz,
1H), 6.78 (d, J ) 8.4 Hz, 1H), 7.57 (dd, J ) 2.4 Hz, J ) 8.4 Hz, 1H),
8.10 (d, J ) 2.4 Hz, 1H), 9.57 (d, J ) 7.6 Hz, 1H, -NH); C NMR
(100 MHz, CDCl ) δ 14.81, 15.41, 24.48, 24.51, 25.77, 32.64, 32.71,
9
1
3
further purification. The erythro-amino alcohols 1 are ∼85% determined
by HPLC.
3
General Procedure for the Preparation of 2-Oxazolidinethione (2).
To a thick solution of erythro-amino alcohol 1 (5 mmol) in 20 mL of
aqueous 2 M sodium carbonate was added CS (7.5 mmol). The reaction
2
mixture was stirred under reflux until the system became transparent.
After cooling to room temperature, the reaction mixture was extracted
with dichloromethane. The combined organic layers were dried over
49.82, 58.91, 62.30, 81.68, 111.31, 120.90, 136.78, 145.25, 150.01,
+
164.52, 184.95; HRMS (ESI) calculated for C18
364.1695, found 364.1691.
H
26
N
3
O
3
S [M + H ]
Data for 3f: yield, 92%; mp, 149.4-150.7 °C; IR (KBr) Vmax (cm-1)
1
3152, 2987, 1693, 1601, 1544, 1297, 1195; H NMR (400 MHz, CDCl
3
)
δ 1.08 (d, J ) 6.4 Hz, 3H), 1.52 (t, J ) 7.0 Hz, 3H), 4.14 (q, J ) 7.0
Hz, 2H), 5.16-5.26 (m, 1H), 5.85 (d, J ) 7.6 Hz, 1H), 6.91 (d, J )
8.0 Hz, 1H), 6.96 (t, J ) 7.6 Hz, 1H), 7.07 (ddd, J ) 1.6 Hz, J ) 7.6
Hz, J ) 8.0 Hz, 1H), 7.44 (d, J ) 8.4 Hz, 1H), 7.73 (dd, J ) 2.8 Hz,
J ) 8.4 Hz, 1H), 8.23 (dd, J ) 1.6 Hz, J ) 8.0 Hz, 1H), 8.41 (d, J )
4
anhydrous MgSO , and then the solvent was removed under reduced
pressure to afford crude products, which were recrystallized from
ethanol/hexane to provide 2-oxazolidinethiones 2 in the range of 55-
7
0% yields.
2.8 Hz, 1H), 11.76 (s, 1H, -NH); 13C NMR (125 MHz, CDCl
) δ
General Procedure for the Preparation of 3-Aminocarbonyl-2-
3
oxazolidinethione (3). A 1.0 mmol amount of 2-oxazolidinethiones 2
was dissolved in 15 mL of CHCl . Several drops of DBU and 1.0 mmol
15.10, 15.16, 58.57, 64.43, 80.47, 111.17, 119.94, 120.77, 124.47,
3
124.47, 126.96, 127.66, 136.64, 147.54, 147.91, 148.52, 152.46, 183.94;
+
of cyclohexyl or substituted phenyl isocyanate were added to the stirred
solution. The reaction was stirred at 0 °C to room temperature for 0.5-2
h. Then, the solvent was evaporated under vacuum, and the residue
was purified via column chromatography on silica gel by using
petroleum ether and acetone as eluent to give pure cis-compounds 3 in
the range of 50-92% yields. The cis-conformation was supported by
the observation of a NOE cross-peak between the two conjoined H of
the 2-oxazolidinethione ring.
HRMS (ESI) calculated for C18
392.0823.
H
19ClN
3
O
3
S [M + H ] 392.0836, found
Data for 3g: yield, 77%; mp, 110.6-112.0 °C; IR (KBr) Vmax (cm-1)
3106, 2978, 1704, 1602, 1541, 1296, 1193; H NMR (400 MHz, CDCl
1
3
)
δ 1.12 (d, J ) 6.8 Hz, 3H), 1.41 (t, J ) 7.0 Hz, 3H), 1.52 (t, J ) 7.0
Hz, 3H), 4.13 (q, J ) 7.0 Hz, 2H), 4.38 (q, J ) 7.0 Hz, 2H), 5.07-
5.16 (m, 1H), 5.79 (d, J ) 7.6 Hz, 1H), 6.79 (d, J ) 8.6 Hz, 1H), 6.90
(d, J ) 8.0 Hz, 1H), 6.96 (dd, J ) 6.8 Hz, J ) 8.0 Hz, 1H), 7.06 (dd,
J ) 6.8 Hz, J ) 8.0 Hz, 1H), 7.60 (dd, J ) 2.4 Hz, J ) 8.6 Hz, 1H),
8.13 (d, J ) 2.4 Hz, 1H), 8.25 (d, J ) 8.0 Hz, 1H), 11.82 (s, 1H,
Data for 3a: yield, 68%; mp, 91.4-92.4 °C; IR (KBr) Vmax (cm-1)
1
3
226, 2933, 1707, 1591, 1538, 1299, 1190; H NMR (400 MHz, CDCl
3
)
-NH); 13C NMR (125 MHz, CDCl
) δ 14.58, 15.10, 15.10, 58.89,
δ 0.96 (d, J ) 6.4 Hz, 3H), 1.22-1.47 (m, 5H), 1.50-1.62 (m, 1H),
3
1
5
.62-1.80 (m, 2H), 1.82-2.00 (m, 2H), 3.74-3.87 (m, 1H), 5.20-
.30 (m, 1H), 5.84 (d, J ) 8.0 Hz, 1H), 7.30 (dd, J ) 5.0 Hz, J ) 7.4
62.23, 64.43, 81.56, 111.15, 111.30, 119.97, 120.78, 120.78, 124.32,
127.15, 136.83, 145.21, 148.19, 148.56, 164.54, 184.56; HRMS (ESI)
+
Hz, 1H), 7.57 (d, J ) 7.8 Hz, 1H), 7.79 (dd, J ) 7.4 Hz, J ) 7.8 Hz,
calculated for C20
H
24
N O
3
4
S [M + H ] 402.1488, found 402.1470.
H), 8.62 (d, J ) 5.0 Hz, 1H), 9.58 (d, J ) 7.2 Hz, 1H, -NH); 13
) δ 14.92, 24.28, 24.31, 25.55, 32.45, 32.51,
C
Data for 3h: yield, 82%; mp, 133.0-134.2 °C; IR (KBr) Vmax (cm-1)
3191, 2934, 1704, 1580, 1539, 1295, 1190; H NMR (400 MHz, CDCl
1
1
NMR (125 MHz, CDCl
3
3
)
4
1
9.62, 58.57, 82.78, 120.81, 123.49, 137.04, 149.57, 149.88, 153.53,
δ 0.97 (d, J ) 6.8 Hz, 3H), 1.25-1.52 (m, 5H), 1.520-1.67 (m, 1H),
1.67-1.83 (m, 2H), 1.83-2.05 (m, 2H), 3.70-3.90 (m, 1H), 5.31-
5.46 (m, 1H), 5.92 (d, J ) 7.6 Hz, 1H), 7.38 (dd, J ) 4.8 Hz, J ) 7.8
+
22 3 2
84.81; HRMS (ESI) calculated for C16H N O S [M + H ] 320.1433,
found 320.1429.
Data for 3b: yield, 92%; mp, 125.9-127.8 °C; IR (KBr) Vmax (cm-1)
Hz, 1H), 7.99 (d, J ) 7.8 Hz, 1H), 8.45 (d, J ) 4.8 Hz, 1H), 9.52 (d,
1
13
3208, 2929, 1700, 1590, 1540, 1294, 1194; H NMR (400 MHz, CDCl
3
)
J ) 7.6 Hz, 1H, -NH); C NMR (100 MHz, CDCl
3
) δ 15.38, 24.42,
δ 1.01 (d, J ) 6.8 Hz, 3H), 1.22-1.52 (m, 5H), 1.54-1.64 (m, 1H),
1
5
24.48, 25.74, 32.59, 32.68, 49.80, 57.46, 79.94, 122.79, 128.59, 136.53,
.66-1.82 (m, 2H), 1.86-2.05 (m, 2H), 3.70-3.87 (m, 1H), 5.04-
.21 (m, 1H), 5.86 (d, J ) 7.6 Hz, 1H), 7.42 (d, J ) 8.4 Hz, 1H), 7.70
148.36, 149.71, 150.01, 184.05; HRMS (ESI) calculated for C16
H
21
-
+
ClN
3
O
2
S [M + H ] 354.1043, found 354.1053.
Data for 3i: yield, 77%; oil; IR (film) Vmax (cm-1) 3214, 2931, 1705,
(
dd, J ) 2.4 Hz, J ) 8.4 Hz, 1H), 8.38 (d, J ) 2.4 Hz, 1H), 9.49 (d,
13
1
J ) 6.8 Hz, 1H, -NH); C NMR (100 MHz, CDCl
2
1
3
) δ 15.34, 24.30,
1591, 1292, 1180; H NMR (400 MHz, CDCl
3
) δ 0.92 (d, J ) 6.4 Hz,
4.33, 25.58, 32.44, 32.51, 49.67, 58.42, 80.43, 124.31, 127.71, 136.53,
3H), 1.20-1.49 (m, 5H), 1.53-1.63 (m, 1H), 1.66-1.78 (m, 2H), 1.88-
2.00 (m, 2H), 3.74-3.86 (m, 1H), 3.98 (s, 3H), 5.17-5.27 (m, 1H),
5.79 (d, J ) 7.6 Hz, 1H), 6.98 (dd, J ) 5.2 Hz, J ) 7.6 Hz, 1H), 7.81
47.46, 149.52, 152.19, 184.15; HRMS (ESI) calculated for C16
H
21
-
+
ClN
3
O
2
S [M + H ] 354.1043, found 354.1032.
Data for 3c: yield, 85%; mp, 124.7-125.7 °C; IR (KBr) Vm 1a x (cm-1)
(d, J ) 7.6 Hz, 1H), 8.18 (d, J ) 5.2 Hz, 1H), 9.59 (d, J ) 7.2 Hz,
13
3
211, 2934, 1704, 1609, 1578.18, 1539, 1287, 1254, 1200; H NMR
1H, -NH); C NMR (125 MHz, CDCl
3
) δ 14.78, 24.24, 24.29, 25.56,
(400 MHz, CDCl
3
) δ 1.04 (d, J ) 6.8 Hz, 3H), 1.23-1.48 (m, 5H),
32.41, 32.51, 49.54, 53.70, 57.73, 79.45, 116.24, 116.81, 135.20, 147.10,
1
3
1
9
2
1
.50-1.64 (m, 1H), 1.64-1.80 (m, 2H), 1.86-2.03 (m, 2H), 3.73-
.84 (m, 1H), 3.95 (s, 3H), 4.96-5.07 (m, 1H), 5.74 (d, J ) 7.6 Hz,
H), 6.80 (d, J ) 8.0 Hz, 1H), 7.57 (d, J ) 8.0 Hz, 1H), 8.12 (s, 1H),
150.02, 159.85, 184.76; HRMS (ESI) calculated for C17
H
24
N
3
O
3
S [M
+
+ H ] 350.1538, found 350.1552.
Data for 3j: yield, 70%; oil; IR (film) Vmax (cm-1) 3219, 2933, 1708,
13
1
.57 (d, J ) 6.4 Hz, 1H, -NH); C NMR (125 MHz, CDCl
3
) δ 15.19,
1592, 1538, 1279, 1177; H NMR (400 MHz, CDCl
3
) δ 0.94 (d, J )
4.25, 24.30, 25.54, 32.44, 32.51, 49.65, 53.84, 58.74, 81.47, 111.21,
6.4 Hz, 3H), 1.20-1.49 (m, 5H), 1.52-1.67 (m, 1H), 1.67-1.78 (m,
2H), 1.84-2.01 (m, 2H), 3.70-3.85 (m, 1H), 4.71-4.85 (m, 2H), 5.18-
5.26 (m, 1H), 5.85 (d, J ) 7.6 Hz, 1H), 7.10 (dd, J ) 5.2 Hz, J ) 7.4
21.12, 136.84, 145.08, 149.96, 164.71, 184.93; HRMS (ESI) calculated
+
for C17
H N
24 3
O
3
S [M + H ] 350.1538, found 350.1528.
Data for 3d: yield, 80%; mp, 106.0-107.2 °C; IR (KBr) Vmax (cm-1)
195, 2927, 1698, 1614, 1550, 1495, 1255, 1166; H NMR (400 MHz,
Hz, 1H), 7.88-7.93 (m, 1H), 8.18 (dd, J ) 1.2 Hz, J ) 5.2 Hz, 1H),
1
13
3
9.55 (d, J ) 7.6 Hz, 1H, -NH); C NMR (125 MHz, CDCl
3
) δ 14.90,
CDCl
3
) δ 1.03 (d, J ) 6.4 Hz, 3H), 1.22-1.50 (m, 5H), 1.54-1.67
24.28, 24.33, 25.57, 32.44, 32.54, 57.82, 62.11 (q, J ) 35.8 Hz), 78.82,
116.55, 118.60, 120.45, 123.40 (q, J ) 275.8 Hz), 136.31, 146.93,
(m, 1H), 1.67-1.82 (m, 2H), 1.90-2.03 (m, 2H), 3.68-3.87 (m, 1H),
4
1
8
.77 (q, J ) 8.4 Hz, 2H), 4.79-5.10 (m, 1H), 5.76 (d, J ) 7.6 Hz,
H), 6.94 (d, J ) 8.4 Hz, 1H), 7.65 (dd, J ) 2.0 Hz J ) 8.4 Hz, 1H),
.13 (d, J ) 2.0 Hz, 1H), 9.54 (d, J ) 7.6 Hz, 1H, -NH); 13C NMR
149.90, 157.40, 184.54; HRMS (ESI) calculated for C18
H
23
F
3
N
3
O
3
S
+
[M + H ] 418.1412, found 418.1426.
Data for 3k: yield, 69%; oil; IR (film) Vmax (cm-1) 3213, 2931, 1706,
1
(100 MHz, CDCl
3
) δ 15.39, 24.46, 24.49, 25.73, 32.61, 32.68, 49.83,
1589, 1538, 1292, 1176; H NMR (400 MHz, CDCl
3
) δ 0.94 (d, J )
5
2
8.79, 62.48 (q, J ) 35.8 Hz), 81.22, 111.37, 122.99, 123.58 (q, J )
6.4 Hz, 3H), 1.22-1.48 (m, 8H), 1.59-1.63 (m, 1H), 1.66-1.78 (m,
2H), 1.88-2.00 (m, 2H), 3.75-3.85 (m, 1H), 4.34-4.51 (m, 2H), 5.16-
5.26 (m, 1H), 5.81 (d, J ) 7.6 Hz, 1H), 6.95 (dd, J ) 4.8 Hz, J ) 7.6
75.8 Hz), 137.48, 144.80, 149.89, 162.26, 184.70; HRMS (ESI)
+
calculated for C18
H
23
F N
3 3
O
3
S [M + H ] 418.1412, found 418.1403.
-1
Data for 3e: yield, 79%; mp, 112.6-113.5 °C; IR (KBr) Vmax (cm
188, 2933, 1679, 1611, 1558.90, 1293, 1196; H NMR (400 MHz,
)
Hz, 1H), 7.80 (d, J ) 7.6 Hz, 1H), 8.16 (d, J ) 4.8 Hz, 1H), 9.60 (d,
1
13
3
J ) 7.6 Hz, 1H, -NH); C NMR (125 MHz, CDCl
3
) δ 14.65, 14.83,

Herbicidal 3-Aminocarbonyl-2-oxazolidinethione Derivatives
J. Agric. Food Chem., Vol. 54, No. 1, 2006 127
2
1
4.24, 24.29, 25.57, 32.40, 32.51, 49.59, 57.81, 62.17, 79.51, 116.25,
Table 1. Herbicidal Activity of Compounds 3a at 100 mg L-1
16.60, 135.27, 147.06, 150.08, 159.59, 184.80; HRMS (ESI) calculated
+
for C18
H N
26 3
O
3
S [M + H ] 364.1695, found 364.1678.
av growth inhibitory rate (%) against
Data for 3l: yield, 85%; mp, 151.4-152.0 °C; IR (KBr) Vmax (cm-1)
E. crus-
galli
S.
vulgare
D. sanguin-
nalis
E. pro-
strasta
C.
sativus
B.
1
3157, 2978, 1703, 1604, 1541, 1294, 1189; H NMR (400 MHz, CDCl
3
)
compd
campestris
δ 1.04 (d, J ) 6.4 Hz, 3H), 1.52 (t, J ) 6.8 Hz, 3H), 4.14 (q, J ) 6.8
Hz, 2H), 5.46-5.55 (m, 1H), 5.98 (d, J ) 7.6 Hz, 1H), 6.91 (d, J )
3
3
3
3
3m
3p
a
d
f
70
80
90
50
90
60
0
60
70
0
30
70
70
70
80
80
80
70
80
80
90
20
85
80
0
40
90
0
20
20
0
40
90
0
80
50
8
.0 Hz, 1H), 6.94-7.01 (m, 1H), 7.08 (ddd, J ) 1.6 Hz, J ) 7.6 Hz,
J ) 8.0 Hz, 1H), 7.39 (dd, J ) 4.8 Hz, J ) 8.0 Hz, 1H), 8.034 (dd, J
1.2 Hz, J ) 8.0 Hz, 1H), 8.26 (dd, J ) 1.6 Hz, J ) 8.0 Hz, 1H),
.46 (dd, J ) 1.2 Hz, J ) 4.8 Hz, 1H), 11.78 (s, 1H, -NH); 13C NMR
125 MHz, CDCl ) δ 15.10, 15.10, 57.44, 64.42, 79.84, 111.14, 119.97,
g
)
8
(
3
1
1
3
20.82, 122.78, 124.39, 127.04, 128.47, 136.57, 147.92, 148.33, 148.51,
a
Only the results of effective compounds are listed.
+
50.05, 183.68; HRMS (ESI) calculated for C18
92.0836, found 392.0834.
3 3
H19ClN O S [M + H ]
RESULTS AND DISCUSSION
Data for 3m: yield, 80%; mp, 122.0-122.8 °C; IR (KBr) Vmax (cm-1)
1
3189, 2931, 1696, 1600, 1557, 1293, 1198; H NMR (400 MHz, CDCl
3
)
Synthesis. The title cis-compounds 3 were synthesized as
shown in Scheme 1. The starting materials erythro-amino
alcohols 1 were prepared by reduction of the corresponding
aminoketones with sodium borohydride in methanol at 0 °C.
The reaction of erythro-1 with CS2 in a basic medium led to
the corresponding cis-2-oxazolidinethiones 2 in the range of 55-
δ 0.98 (d, J ) 6.4 Hz, 3H), 1.25-1.48 (m, 5H), 1.54-1.62 (m, 1H),
1
5
.67-1.78 (m, 2H), 1.90-2.00 (m, 2H), 3.73-3.84 (m, 1H), 5.08-
.18 (m, 1H), 5.76 (d, J ) 8.0 Hz, 1H), 7.29 (d, J ) 5.6 Hz, 2H), 8.70
1
3
(
d, J ) 5.6 Hz, 2H), 9.52 (d, J ) 7.2 Hz, 1H, -NH); C NMR (125
MHz, CDCl ) δ 15.00, 24.25, 24.28, 25.51, 32.41, 32.49, 49.68, 58.21,
1.42, 120.71, 141.82, 149.74, 150.24, 184.46; HRMS (ESI) calculated
3
8
7
0% yields (15). The further reaction of intermediates 2 with
+
22 3 2
for C16H N O S [M + H ] 320.1433, found 320.1429.
cyclohexyl or substituted phenyl isocyanate could proceed
readily at or below room temperature under a moisture-free
condition to give target compounds 3. The yields of compounds
Data for 3n: yield, 75%; mp, 129.5-130.7 °C; IR (KBr) Vmax (cm-1)
1
3146, 2969, 1701, 1594, 1542, 1287, 1174; H NMR (400 MHz, CDCl
3
)
δ 1.06 (d, J ) 6.4 Hz, 3H), 5.19-5.27 (m, 1H), 5.84 (d, J ) 7.6 Hz,
H), 7.10 (ddd, J ) 1.6 Hz, J ) 8.0 Hz, J ) 8.0 Hz, 1H), 7.27-7.31
m, 1H), 7.32 (d, J ) 6.0 Hz, 2H), 7.43 (dd, J ) 1.6 Hz, J ) 8.0 Hz,
3
could be decreased because isocyanates were active enough
1
(
to easily form the corresponding ureas under a moisture
condition. The variation of substituent R1 at the pyridine ring
also influenced the reaction yield, and the yield of reaction
toward compounds 3 slightly decreased with the increasing
electron-donating ability of R1 and the increasing electron
density on the pyridine ring. The structures of the title
1
1
8
1
H), 8.21 (dd, J ) 1.6 Hz, J ) 8.0 Hz, 1H), 8.72 (d, J ) 6.0 Hz, 2H),
13
1.75 (s, 1H, -NH); C NMR (125 MHz, CDCl
3
) δ 14.89, 58.46,
1.61, 120.67, 122.49, 124.68, 125.46, 127.44, 129.62, 134.29, 141.49,
48.39, 150.33, 184.19; HRMS (ESI) calculated for C16
3 2
H15ClN O S
+
[M + H ] 348.0574, found 348.0580.
Data for 3o: yield, 90%; mp, 140.5-141.7 °C; IR (KBr) Vmax (cm-1)
1
13
compounds were well characterized by H NMR, C NMR,
IR, and HRMS.
1
3170, 2978, 1704, 1605, 1554, 1296, 1179; H NMR (400 MHz, CDCl
3
)
δ 1.04 (d, J ) 6.4 Hz, 3H), 1.52 (t, J ) 7.0 Hz, 3H), 4.14 (q, J ) 7.0
Hz, 2H) 5.19-5.28 (m, 1H), 5.81 (d, J ) 7.6 Hz, 1H), 6.91 (dd, J )
Biological Activity. As shown in Table 1, compounds 3a,
d, 3f, 3g, 3m, and 3p exhibited considerable inhibitory activity
3
1
.2 Hz, J ) 8.0 Hz, 1H), 6.77 (ddd, J ) 1.2 Hz, J ) 7.6 Hz, J ) 8.0
against both dicotyledonous and monocotyledonous weeds, and
their herbicidal activities against E. crusgalli, D. sanguinalis,
and E. prostrasta were greater than those against S. Vulgare,
C. satiVus, and B. campestris. The inhibitory activity of
compound 3f against some test plants reached 90% at 100 mg
Hz, 1H), 7.08 (ddd, J ) 1.6 Hz, J ) 7.6 Hz, J ) 8.0 Hz, 1H), 7.32 (d,
J ) 6.0 Hz, 2H), 8.24 (dd, J ) 1.6 Hz, J ) 8.0 Hz, 1H), 8.71 (d, J )
1
3
6
1
1
.0 Hz, 2H), 11.78 (s, 1H, -NH); C NMR (125 MHz, CDCl ) δ
3
4.91, 15.09, 58.34, 64.42, 81.45, 111.16, 119.93, 120.68, 120.75,
24.43, 127.00, 141.65, 147.96, 148.53, 150.33, 184.06; HRMS (ESI)
+
-1
calculated for C18
H N O
20 3 3
S [M + H ] 358.1225, found 358.1230.
L . Compounds with an X group at the 2-, 3- and 4- positions
Data for 3p: yield, 50%; mp, 136.4-137.8 °C; IR (KBr) Vmax (cm-1)
of the pyridine ring possess some herbicidal activity (3a, 3d,
3m), but it was obvious that the compounds having substituents
at the ortho-position of the X group (3h-3l) did not show any
herbicidal activities.
Although we have no information about the mode of action
of these compounds, it was presumed that their mode of action
is possibly concerned with the photosynthesis system according
to the symptoms of the yellow of E. crusgalli’s leaf and the
albinism of the weed. Further research on the modification of
structure and the mode of action is in progress.
Structure-Activity Relationship. It is well-known that the
steric property is one of the factors affecting biological activities
of compounds. The dihedral angles, expressing the steric
property, were calculated by using a molecular modeling
program, PCMODEL 6.), of Serena Software (Table 2). Before
all parameters of a compound were calculated, it was essential
that its spatial molecular conformation be optimized with
PCMODEL to acquire its most relaxed conformation. For
example, for compound 3h, the dihedral angle was indicated
as the C1-C2-C3-O dihedral angle or the C1-C2-C3-C4
dihedral angle (Figure 1). From Table 2, it was found that with
compounds having no substituent at the ortho-position of the
X group (3a-3g, 3m-3p), their dihedral angles are smaller
1
3
110, 2970, 1704, 1606, 1581, 1269, 1168; H NMR (400 MHz, CDCl
3
)
δ 1.05 (d, J ) 6.4 Hz, 3H), 5.15-5.25 (m, 1H), 5.84 (d, J ) 7.6 Hz,
1
H), 7.28-7.35 (m, 3H), 7.66 (dd, J ) 7.2 Hz, J ) 8.4 Hz, 1H), 8.12
(
d, J ) 8.4 Hz, 1H), 8.21 (d, J ) 8.0 Hz, 1H), 8.73 (d, J ) 6.0 Hz,
13
2
5
1
H), 12.42 (s, 1H, -NH); C NMR (125 MHz, CDCl
3
) δ 14.84, 16.75,
8.68, 81.52, 120.69, 125.10, 125.58, 131.83, 134.39, 140.49, 141.49,
49.10, 150.34, 183.80; HRMS (ESI) calculated for C16
15 4 4
H N O S [M
+
+
H ] 359.0814, found 359.0814.
Biological Assay. The herbicidal activities of compounds 3 were
measured with the method described as follows. Each sample was
dissolved in DMF, and then the solution was diluted with emulsifier
0
201 (a mixture of anionic and nonionic surfactant) containing water
-1
(0.1 g L ) until the required concentration was achieved. The biological
tests were carried out in plastic boxes. Nineteen milliliters of 0.9%
thawed water agar and a 1 mL of diluted solution were added to the
plastic boxes and shaken. After the drug-containing agar was cool, the
seeds of Echinochloa crusgalli, Sorghum Vulgare, Digitaria sanguin-
nalis, Eclipta prostrasta, Cucumis satiVus, and Brassica campestris were
sowed, and then the cultivations were kept at 24 ( 1 °C with exposure
to light of 3000 lx for 7 days. The root growth inhibitory rates (percent)
of compounds 3 related to the control were determined. The experiments
were conducted in three replicates with 150 seeds per plant for each
concentration. The results of compounds 3 demonstrating activity are
listed in Table 1.

128 J. Agric. Food Chem., Vol. 54, No. 1, 2006
Li et al.
Scheme 1. Synthesis Route of Compounds 3
Table 2. Molecular Parameters Calculated by PCMODEL
dihedral angle (deg)
compd
V
T
(Å2)
V
P
(Å2)
V
N
(Å2)
V /V
N P
1
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
432.964
435.943
456.498
513.870
494.282
489.117
536.868
439.242
459.685
488.141
489.383
484.274
422.590
416.631
473.776
417.593
99.958
103.458
106.838
110.889
104.519
112.740
122.241
104.876
102.079
101.186
103.270
112.071
96.458
333.006
332.485
349.660
402.981
389.763
376.377
414.627
334.366
357.606
386.955
386.113
372.203
326.132
311.418
359.420
264.950
3.331
3.214
3.273
3.634
3.729
3.338
3.392
3.188
3.503
3.824
3.739
3.321
3.381
2.960
3.143
1.736
164.1
158.5
157.2
161.3
160.3
159.0
162.0
164.7
170.1
179.5
171.9
166.2
163.2
153.3
159.3
159.3
−80.2
−85.5
−86.7
−82.6
−83.7
−84.9
−81.9
−79.4
−73.5
−63.6
−71.5
−77.9
−79.7
−91.0
−84.8
−85.0
Figure 1. Molecular model of compound 3h based on MMX-E of
PCMODEL 6.0 software.
105.213
114.356
152.643
the dihedral angle rule but are inactive because their VN/VP
values lie outside the acceptable range. On the contrary,
compound 3i obeys the lipophilicity rule but also is inactive
because its dihedral angles lie outside the acceptable range. On
the basis of the above discussion, the combination of appropriate
steric property and proper lipophilicity is necessary for herbicidal
activity. However, nitro compound 3p did not obey the
lipophilicity rule (1.736) but is active, and this might be due to
its probably different mode of action from the other non-nitro
compounds.
than 164.1° or -79.4°. Compared with H, the ortho-substituent
of the X group is big enough to make the dihedral angle bigger
than 164.7° or -79.4°. Therefore, it is a premise of compounds
3
possessing activity that the dihedral angle remains in the range
from 153.3° to 164.1° or from -91.0° to -79.7°.
On the other hand, it has been proposed that a certain degree
of lipophilicity is necessary for compounds with bioactivities
because the strongly polar compounds would not be allowed to
cross the membranes and extremely low water-soluble com-
pounds would not be soluble enough. The molecular lipophilicity
parameters VN/VP, where VT, VN, and VP stand for the total
surface area, nonpolar surface area, and polar surface area of
the water solvation shell, respectively, were also calculated
In conclusion, we have demonstrated that the novel com-
pounds of 3-aminocarbonyl-2-oxazolidinethione containing a
substituted pyridine ring presented good herbicidal activity. It
was found that the activities of such compounds against E.
crusgalli, S. Vulgare, D. sanguinnalis, E. prostrasta, C. satiVus,
and B. campestris can be strongly related to the lipophilicity
together with the steric property. Future structural modification
and biological evaluation should be carried out to explore the
full potential of this novel class of herbicidal molecules.
(Table 2).
From Table 2, it was found that VN/VP is a very important
parameter influencing the activity, and the suitable VN/VP value
of compounds 3 with herbicidal activities should remain in the
range of 3.331-3.634. Compounds 3b, 3c, 3e, 3n, and 3o obey

Herbicidal 3-Aminocarbonyl-2-oxazolidinethione Derivatives
J. Agric. Food Chem., Vol. 54, No. 1, 2006 129
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JF051928J