Synthesis of silicon-containing azole derivatives with magnesium bromide diethyl etherate, and an investigation of their fungicidal activities

Article abstract of DOI:10.1016/S0968-0896(02)00302-4

Enhancement of magnesium bromide diethyl etherate in addition reaction of trimethylsilylmethylmagnesium chloride 5 to 2-(1H-1,2,4-triazol-1-yl)acetophenones 6 allowed us to prepare silicon-containing azole derivatives, which were tested for fungicidal act

Full text of DOI:10.1016/S0968-0896(02)00302-4

Bioorganic & Medicinal Chemistry 10 (2002) 4029–4034
Synthesis of Silicon-Containing Azole Derivatives with
Magnesium Bromide Diethyl Etherate, and an
Investigation of Their Fungicidal Activities
a,
a
a
a
Hiroyuki Itoh, * Hisaki Kajino, Takahiro Tsukiyama, Junzo Tobitsuka,
a
a
a
b
Hiroshi Ohta, Yukiyoshi Takahi, Mikio Tsuda and Hideo Takeshiba
aAgroscience Research Laboratories, Sankyo Co., Ltd., Yasu, 1041, Yasu, Yasu-cho, Yasu-gun, Shiga-ken, 520-2342, Japan
bMedicinal Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi, 1-chome, Shinagawa-ku, Tokyo, 140-8710, Japan
Received 15May 2002; accepted 3 July 2002
Abstract—Enhancement of magnesium bromide diethyl etherate in addition reaction of trimethylsilylmethylmagnesium chloride 5
to 2-(1H-1,2,4-triazol-1-yl)acetophenones 6 allowed us to prepare silicon-containing azole derivatives, which were tested for fungi-
cidal activity and phytotoxicity. Among them, 2-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-trimethylsilylpropan-2-ol 1a was
determined to be the most effective and potential candidate for novel fungicide.
#
2002 Elsevier Science Ltd. All rights reserved.
Introduction
fungi, Pyricularia oryzae and Rhizoctonia solani,
respectively. Because these fungi also contain ergosterol
in their cell membrane, azole fungicides were expected
to show efficacy against these diseases on rice plant.
Contrary to expectation, no azole fungicides were used
for these diseases. Commercial azole fungicides were
observed phytotoxicity for rice plant by our tests. It
may be the reason why there have been no azole fungi-
cides developed for rice plant so far. When we try to test
the actions of the azole derivatives on rice plant, the
phytotoxicity must be checked at the same time.
In the course of our research on azole fungicides, we
synthesized a series of silicon-containing azole deriva-
tives 1 and found that they exerted a remarkably potent
activity against rice sheath blight in submerged applica-
tion. However, the low yields of 1 discourage us to
allow any further evaluation.
1
Azole fungicides inhibit the fungal biosynthesis of
ergosterol, an important constituent of fungal cell
membrane, and this has led to their use for the control of
2
a wide range of diseases. Most of the azole fungicides
have been developed for diseases on cereal crops, such
Disclosed herein is a convenient and efficient method to
synthesize the silicon-cotaining azole derivatives and
their evaluation for fungicidal activities against rice
blast, rice sheath blight and powdery mildew on barley
together with phytotoxicity.
3
4
as cyproconazole and tebuconazole for powdery mildew
5
6
on cereal, and epoxiconazole and flusilazole for rust
on cereal as shown in Figure 1. These situations
prompted us to evaluate the synthesized derivatives for
fungicidal activity against powdery mildew on cereal.
Chemistry
Powdery mildew on cereal is a disease caused by Ery-
siphe graminis. The fungus belongs to filamentous fungi,
which contain ergosterol in their cell membrane. On the
other hand, rice blast and rice sheath blight, which are
devastating diseases to rice plant, caused by filamentous
7
The general synthetic method to prepare azole compounds
such as 3 was to open the epoxides 2 with 1,2,4-triazole.
However, under these conditions, our derivatives 1 were
1
easily decomposed into allyl compounds 4 (Fig. 2).
The addition of organometallic reagents to a (1-H-1,2,4-
triazol-1-yl)acetophenone was attempted in special
*
2
Corresponding author. Tel.: +81-77-586-1223; fax: +81-77-586-
538; e-mail: hiroit@yasu.sankyo.co.jp
0
968-0896/02/$ - see front matter # 2002 Elsevier Science Ltd. All rights reserved.
PII: S0968-0896(02)00302-4

4030
H. Itoh et al. / Bioorg. Med. Chem. 10 (2002) 4029–4034
Figure 1. Silicon-containing azole derivatives 1 and other azole fungicides.
Figure 2. General synthetic method to prepare azole compound.
cases. For example, Chollet et al. reported the additions
of alkenylaluminum halide and alkenylzinc halide to the
Based on these observations, we presumed that the
2-nitrogen atom on the 1H-1,2,4-triazole ring is attribu-
table to the failure of the Grignard reaction with 6. A
tentative explanation is that the magnesium atom of the
Grignard reagent forms a chelate with the 2-nitrogen
atom on the 1H-1,2,4-triazole ring (Fig. 5). The forma-
tion of this complex could facilitate deprotonation of the
acetophenone to give the enolate species. Based on this
hypothesis, we added the Grignard reagent 5 to 6 in the
presence of magnesium bromide diethyl etherate in the
hope that the magnesium ion would prevent the forma-
tion of such a chelate and increase the amount of the
desired product.
8
acetophenones, and Dickinson et al. and Eto et al.
9
reported the addition of heteroaralkyllithium.
1
In our previous study, we synthesized compounds 1 by
adding trimethylsilylmethyl Grignard reagent 5 to (1H-
1
,2,4-triazol-1-yl)acetophenones 6 (Fig. 3). Regretfully,
the compounds were formed in very low yields no matter
how we varied the temperature, concentration of the
Grignard reagent, and the ratio of the Grignard reagent
and the acetophenone. On the other hand, the Grignard
reaction with 2-(imidazol-1-yl)acetophenone 7 produced
compounds 8 in fair yields (Fig. 4, Table 1).
1
0
Figure 3. Silicon-containing triazole compounds prepared by the
Grignard reaction.
Figure 4. Silicon-containing imidazole compounds prepared by the
Grignard reaction.

H. Itoh et al. / Bioorg. Med. Chem. 10 (2002) 4029–4034
4031
Table 1. Synthesis of imidazole derivatives 8
Our trial produced promising results, in which 5 reacted
with the carbonyl group of 6 to give adducts 1 in better
yields (Table 2). Moreover, the other aliphatic Grignard
reagents also provided addition products 9 in fair yields
Entry no.
X
8
ꢀ
Yield (%)
mp ( C)
(
Fig. 6, Table 3).
a
b
c
d
e
f
4-F
4-Cl
2,4-Cl
2,4-F
H
4-Me
74a
84
59
97
93
89
123a
108–10
125–127
112–114
86–87
Magnesium bromide diethyl etherate has the potential
to work as a Lewis acid and activate the carbonyl
group. However, the use of the other Lewis acids such
as aluminum chloride, zinc chloride and boron tri-
fluoride resulted in only the recovery of the starting
material.
2
2
1
1
101
aData from our previous work.1
From the results described above, we surmised that the
magnesium bromide diethyl etherate improved the
yields mainly by preventing the formation of chelation.
Thus, we have discovered a novel and efficient method
to synthesize triazolyl derivatives from (1,2,4-triazol-1-
yl)acetophenones with Grignard reagents in the pre-
sence of magnesium bromide diethyl etherate.
Figure 5. Chelation by the Grignard reagent.
Table 2. Synthesis of triazole derivatives 1
Fungicidal Activities and Discussion
We performed tests on the silicon-containing azole
derivatives obtained by the above-described methods in
order to assess their fungicidal activities against rice
blast, rice sheath blight and powdery mildew of barley,
and also their phytotoxicity and EC50 values against the
phytophathogenic fungi P. oryzae and R. solani. The
results are shown in Table 4.
Entry no.
X
1 Yield (%)
a
Additive (À)
Additive (+)
a
b
c
d
e
f
4-F
4-Cl
2,4-Cl
2,4-F
H
4-Me
7
7
10
16
1532
4
45
41
35
55
2
2
The data for imidazolyl derivatives 8a–8f indicate gen-
erally low fungicidal activities. The substituted com-
pounds on phenyl ring derivatives that appeared active
in vitro were the 2,4-dichloro, 2,4,-difluoro derivatives
27
23
32
23
52
g
h
i
4-OMe
4-CF
4-Br
2-F,4-Cl
13
8
11
6
3
8
c and 8d.
j
aData from our previous work.1
On the other hand, the data for triazolyl derivatives 1a–
j suggest that the 2-nitrogen atom on the 1H-1,2,4-tri-
azole ring is critical for good activity. Compounds 1c,
d and 1j with dihalogen substitution on the phenyl ring
1
1
inhibited the mycelia extension of P. oryzae more
potently than the unsubstituted and mono-substituted
compounds 1a, 1b, 1e, 1f, 1g, 1h and 1i. In our in vitro
tests against R. solani, all triazolyl derivatives were
found to be highly active. Halogen-substituted deriva-
tives applied by foliar spraying had more favorable
fungicidal activities against both rice blast and powdery
mildew on barley. The 4-fluoro derivative 1a was proved
to show maximum activity against rice sheath blight by
submerged application. Some of the substituted com-
pounds were nearly the same active as 1a, but only 1a
was free of phytotoxic effects against rice plant (Table
Figure 6. Triazole compounds prepared by the Grignard reaction.
Table 3. Synthesis of triazole derivatives 9 X=4-F
4). This is a very important point for the development of
an adequate fungicide.
Entry no.
R
Yield (%)
Among silicon-free compounds, compounds with a
straight alkyl chain 9a, 9b exerted weak fungicidal
activities. Compounds with a branched alkyl chain 9c,
9d exhibited enhanced fungicidal activities but phyto-
toxicity was observed in these compounds.
a
b
c
Ethyl
Butyl
Isobutyl
Neopentyl
70
68
39
37
d

4032
H. Itoh et al. / Bioorg. Med. Chem. 10 (2002) 4029–4034
Table 4. Fungicidal activities of azole derivatives
Compd
P.O. IC50
R.B. MIC
(g/10a)
R.S. IC50
(ppm)
S.B. MIC
(g/10a)
P.M. MIC
(ppm)
Phytotoxicity
(ppm)
8
8
8
8
8
8
1
1
1
1
1
1
1
1
1
1
9
9
9
9
a
b
c
d
e
f
a
b
c
d
e
f
6.00
3.53
0.24
0.27
6.60
30
30
30
30
30
30
3
>10
>10
6.50
6.50
>10
>10
0.04
0.08
0.01
0.02
0.09
0.13
nt
>100a
>100
>100
>100
>100
>100
1
1
1
nt
nt
nt
nt
nt
1
>3
>3
0.3
0.1
nt
>3
0.3
3
>3
1
0.1
0.3
nt
>10
1.09
nt
a
12.5
a
À
2.70
0.26
0.38
2.26
3
25
>100
++
++
++
nt
a
>100
3
>100
nt
>100
3
>100
3
a
100
50
a
a
>10
>10
>10
5.89
0.76
>10
>10
6.38
1.82
>100
>100
100
>100
nt
nt
nt
a
g
h
i
a
0.13
0.12
0.04
5.19
2.47
a
++
++
À
a
j
50
>100
>100
a
b
c
d
>100
>100
30
nt
+
0.3525
0.0525
1
1
++
++
100
P.O., Pyricularia oryzae; R.B., Rice blast; R.S., Rhizoctonia solani; S.B., Sheath blight; P.M., Powdery mildew; nt, not tested.
a
1
D
a
t
a
f
r
o
m
o
u
r
p
r
e
v
i
o
u
s
w
o
r
k
.
Conclusion
General procedure for the Grignard reaction in the
absence of magnesium bromide diethyl etherate
In conclusion, we discovered a novel and efficient
method to synthesize silicon-containing triazolyl deri-
vatives from (1,2,4-triazol-1-yl)acetophenones 6 with
Grignard reagents in the presence of magnesium bromide
diethyl etherate. The obtained silicon-containing azole
derivatives showed broad fungicidal activities. Among
them, 2-(4-fluorophenyl)-3-(1H-1,2,4-triazol-1-yl)-1-tri-
methylsilylpropan-2-ol 1a exhibited the most promising
efficacy and safety for rice plant. As a result of this
work, 1a was advanced to commercial development
for the control of fungal infections of rice and other
crops.
1
This general procedure used for our previous work was
applied to this work. A solution of trimethylsilyl-
methylmagnesium chloride (1.0 M) in diethyl ether (13.5
mL, 13.5mmol) was added to a solution of aceto-
phenones (2.7 mmol) in diethyl ether (60 mL). After
stirring for 0.5h, the mixture was refluxed for 6 h,
poured into ice, quenched with an aqueous solution of
ammonium chloride, and extracted with ethyl acetate.
After drying over magnesium sulfate and evaporation of
the solvent, the residue was purified by chromatography
and crystallized from diisopropyl ether.
The same general method was used to prepare the deriv-
atives described below. The yields are given in Table 1.
Experimental
All melting points (mp) were uncorrected. IR was
1
2-(4-Chlorophenyl)-1-(imidazol-1-yl)-3-trimethylsilyl-
ꢀ
À1
recorded on a Perkin-Elmer 1600 spectrometer and H
propan-2-ol (8b). Mp 173–174 C. IR (KBr) cm : 2957,
2700, 1592, 1511, 1491, 1431, 1411, 1289, 1247, 1226,
NMR spectra were recorded on a Varian Gemini 200
spectrometer using tetramethylsilane as an internal
standard. MS were obtained on a JEOL JMS-D300
spectrometer and a VG Auto Spec M mass spectro-
meter. TLC was performed on a plate of precoated with
a 0.25mm-thick layer of silica gel (E. Merck), and the
spots were made visible by ultraviolet (UV) irradiation
or by spraying with a solution made of 25g ammonium
molybdate and 1 g ceric sulfate in 500 mL of 10% sul-
furic acid followed by heating. Silica gel (350–250 mesh,
Yamamura Chemical Laboratories Co., Ltd.) was used
for column chromatography and preparative TLC was
carried out on a plate of precoated with a 2 mm-thick
layer of silica gel (E. Merck). The following abbrevia-
tions are used hereafter: s, singlet; d, doublet; dd,
doublet of doublet; t, triplet; q, quartet; m, multiplet;
br, broad.
1
1178, 1090. H NMR (200 MHz, CDCl ) d: À0.17 (9H,
3
s), 1.19 (1H, d, J=14.8 Hz), 1.39 (1H, d, J=14.8 Hz),
4.09 (2H, s), 6.66 (1H, s), 6.92 (1H, s), 7.25(1H, s),
7.29–7.35(4H, m). MS m/z: 309 (M ), 293, 227, 219,
137. Anal. calcd for C H N OClSi: C, 58.33; H, 6.85;
N, 9.07. Found: C, 58.38; H, 6.65; N, 9.08.
+
1
5
21
2
2-(2,4-Dichlorophenyl)-1-(imidazol-1-yl)-3-trimethylsilyl-
propan-2-ol (8c). Mp 154–156 C. IR (KBr) cm : 3141,
ꢀ
2948, 2892, 1588, 1551, 1511, 1463, 1435, 1287, 1247,
À1
1
1235, 1110. H NMR (200 MHz, CDCl ) d: À0.18 (9H,
3
s), 1.08 (1H, d, J=15.1 Hz), 2.12 (1H, d, J=15.1 Hz),
4.30 (1H, d, J=14.3 Hz), 4.64 (1H, d, J=14.3 Hz), 6.74
(1H, s), 6.89 (1H, s), 7.21 (1H, dd, J=2.2, 8.6 Hz), 7.34
(1H, s), 7.40 (1H, d, J=2.2 Hz), 7.63 (1H, d, J=8.6 Hz).
+
MS m/z: 343 (M ), 327, 253, 171. Anal. calcd for

H. Itoh et al. / Bioorg. Med. Chem. 10 (2002) 4029–4034
4033
C H N OCl Si: C, 52.48; H, 5.87; N, 8.16. Found: C,
1
J=7.6 Hz), 1.75(1H, dt, J=7.6, 14.3 Hz), 1.90 (1H, dt,
J=7.6, 14.3 Hz), 4.37 (1H, d, J=14.3 Hz), 4.45(1H, d,
J=14.3 Hz), 7.00 (2H, t, J=8.7 Hz), 7.28 (2H, dd,
J=5.3, 8.7 Hz), 7.84 (1H, s), 7.88 (1H, s). MS m/z: 235
5
20
2
2
5
2.48; H, 5.60; N, 8.26.
2-(2,4-Difluorophenyl)-1-(imidazol-1-yl)-3-trimethylsilyl-
propan-2-ol (8d). Mp 147–148 C. IR (KBr) cm : 3122,
ꢀ
957, 2900, 1620, 1596, 1515, 1499, 1431, 1415, 1283,
271, 1247, 1231, 1130, 1094, 1078. H NMR (200 MHz,
À1
+
(M ), 206, 164, 123, 109. Anal. calcd for C H FN O:
1
2
14
3
2
1
C, 61.26; H, 6.00; N, 17.86. Found: C, 61.41; H, 5.97; N,
17.71.
1
CDCl ) d: À0.19 (9H, s), 1.12 (1H, d, J=15.0 Hz), 1.64
3
(1H, d, J=15.0 Hz), 4.19 (1H, d, J=14.2 Hz), 4.31 (1H,
d, J=14.2 Hz), 6.742–6.89 (4H, m), 7.38–7.50 (2H, m).
2-(4-Fluorophenyl)-4-methyl-1-(1H-1,2,4-triazol-1-yl)pen-
ꢀ
À1
tan-2-ol (9c). Mp 126–129 C. IR (KBr) cm : 3190,
2958, 2873, 1606, 1512, 1425, 1357, 1224, 1207, 1141,
+
MS m/z: 310 (M ), 295, 229, 131 Anal. calcd for
C H F N OSi: C, 58.04; H, 6.49; N, 9.02. Found: C,
1
1031. H NMR (200 MHz, CDCl ) d: 0.68 (3H, d,
1
5
20
2
2
3
5
8.02; H, 6.44; N, 9.19.
J=6.3 Hz), 0.92 (3H, d, J=6.3 Hz), 1.53–1.70 (2H, m),
1.80–1.88 (1H, m), 4.04 (1H, s), 4.31 (1H, d,
1-(Imidazol-1-yl)-2-pheny-3-trimethylsilylpropan-2-ol (8e).
Mp 178–179 C. IR (KBr) cm : 2957, 2707, 1596,
1
J=14.0 Hz), 4.40 (1H, d, J=14.0 Hz), 6.99 (2H, t,
J=8.5Hz), 7.31 (2H, dd, J=5.5, 8.5 Hz), 7.79 (1H, s),
ꢀ
511, 1443, 1407, 1343, 1283, 1247, 1190, 1108, 1078. H
À1
1
+
7.89 (1H, s). MS m/z: 263 (M ), 206, 181, 164, 139, 121,
109. Anal. calcd for C H FN O: C, 63.86; H, 6.89; N,
15.96. Found: C, 63.90; H, 6.87; N, 15.70.
NMR (200 MHz, CDCl ) d: À0.20 (9H, s), 1.19 (1H, d,
3
14 18
3
J=14.7 Hz), 1.42 (1H, d, J=14.7 Hz), 4.09 (1H, d,
J=14.0 Hz), 4.17 (1H, d, J=14.0 Hz), 6.64 (1H, s), 6.90
(
(
1H, s), 7.23 (1H, s), 7.29–7.35( 5H , m). MS m/z: 275
+
4,4-Dimethyl-2-(4-fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)
pentan-2-ol (9d). Mp 129–133 C. IR (KBr) cm : 3184,
ꢀ
2954, 2858, 1604, 1515, 1361, 1277, 1209, 1143, 1124,
À1
M ), 259, 193, 185, 103. Anal. calcd for C H N OSi:
1
5
22
2
C, 65.65; H, 8.08; N, 10.21. Found: C, 65.61; H, 8.11; N,
1
1
0.23.
1022. H NMR (200 MHz, CDCl ) d: 0.79 (9H, s), 1.72
3
(1H, d, J=14.5Hz), 1.95(1H, d, J=14.5Hz), 4.14 (1H,
1
-(Imidazol-1-yl)-2-(4-methylphenyl)-3-trimethylsilyl-
ꢀ
s), 4.27 (1H, d, J=13.7 Hz), 4.38 (1H, d, J=13.7 Hz),
6.96 (2H, t, J=6.8 Hz), 7.32 (2H, dd, J=7.5, 8.8 Hz),
À1
propan-2-ol (8f). Mp 172–173 C. IR (KBr) cm : 3144,
956, 1511, 1428, 1400, 1283, 1244, 1111, 1078. 1
+
2
H
7.73 (1H, s), 7.87 (1H, s). MS m/z: 277 (M ), 206, 195,
164, 139, 123, 109. Anal. calcd for C H FN O: C,
NMR (200 MHz, CDCl ) d: À0.19 (9H, s), 1.17 (1H, d,
3
15 20
3
J=14.7 Hz), 1.41 (1H, d, J=14.7 Hz), 2.34 (3H, s), 4.06
(
64.96; H, 7.27; N, 15.15. Found: C, 64.87; H, 7.23; N,
14.93.
1H, d, J=15.0 Hz), 4.14 (1H, d, J=15.0 Hz), 6.67 (1H, s),
+
6
.93 (1H, s), 7.11–7.22 (5H, m). MS m/z: 288 (M ), 273,
07, 199, 117. Anal. calcd for C H N OSi: C, 66.62;
2
H, 8.39; N, 9.71. Found: C, 66.88; H, 8.14; N, 9.84.
2-(4-Fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)hexan-2-ol (9b).
1
6
24
2
ꢀ
À1
Mp 94–95 C. IR (KBr) cm : 3178, 2921, 2864, 1604,
510, 1461, 1427, 1276, 1220, 1136, 1089, 1031. 1
NMR (200 MHz, CDCl ) d: 0.82 (3H, t, J=7.0 Hz),
1
H
3
General procedure for the Grignard reaction in the
presence of magnesium bromide diethyl etherate
1.04 (1H, m), 1.15–1.32 (3H, m), 1.68 (1H, m), 1.83 (1H,
m), 4.00 (1H, s), 4.36 (1H, d, J=14.3 Hz), 4.44 (1H, d,
J=14.3 Hz), 6.99 (2H, t, J=7.7 Hz), 7.30 (2H, dd,
J=3.5, 7.7 Hz), 7.83 (1H, s), 7.87 (1H, s). MS m/z: 263
A
(
solution of (1H-1,2,4-triazol-1-yl)acetophenone
1.5mmol) in dichloromethane (2.0 mL) was added to a
suspension of magnesium bromide diethyl etherate
775mg, 3.0 mmol) in dichloromethane (3.0 mL) and
diethyl ether (3 mL) at room temperature and stirred for
.5h. A solution of trimethylsilylmethylmagnesium
+
(M ), 206, 191, 164, 149, 138, 123, 109. Anal. calcd for
C H FN O: C, 63.86; H, 6.89; N, 15.96. Found: C,
63.80; H, 6.80; N, 15.93.
(
1
4
18
3
0
chloride (1.5M) in diethyl ether (2.0 mL, 3.0 mmol) was
ꢀ
Silicon-containing azole derivatives (1a–1j) were
obtained in the same way. The yields are given in Table 2.
added at 0 C. After stirring for 0.5h, the mixture was
poured into ice, quenched with an aqueous solution of
ammonium chloride, and extracted with ethyl acetate.
The organic layer was washed with water and dried over
magnesium sulfate. The solvent was then evaporated,
and the solid remaining was partitioned between toluene
and 1 N HCl. The organic layer was washed with water
and concentrated to yield a residue, and this residue was
purified by chromatography and crystallized from diiso-
propyl ether. The yields are given in Table 3.
Antifungal activity
Four-millimeter mycelial agar discs were placed on
potato dextrose agar plates containing test compounds.
The plates were incubated at 25 C for 7 days as for a
test of P. oryzae or 3 days as for a test of R. solani, and
the diameters of the mycelium colonies were then mea-
sured to examine the effects of the chemicals on fungal
growth. The results are shown in Table 4.
ꢀ
The same general method was used to prepare the deri-
vatives described below.
Curative activity against rice blast
2
-(4-Fluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
Rice seedlings (variety Sachikaze) at the 4–5leaf stage
were sprayed with a spore suspension of the fungus P.
oryzae and kept in a moist chamber (relative humidity:
ꢀ
931, 1602, 1521, 1460, 1415, 1286, 1217, 1163, 1134,
À1
(
9a). Mp 94–96 C. IR (KBr) cm : 3205, 3110, 2970,
2
1
1
ꢀ
099, 1016. H NMR (200 MHz, CDCl ) d: 0.80 (3H, t,
100%) at 20–22 C. After 24 h, the rice seedlings were
3

4034
H. Itoh et al. / Bioorg. Med. Chem. 10 (2002) 4029–4034
sprayed with aqueous suspensions of the test compound
at different concentrations. Placed back in the moist
chamber. The concentration with the highest efficacy
against rice blast was identified after 6 days. The results
are shown in Table 4.
of growth inhibition; +, from 10 to 30% of growth
inhibition; À less than 10% of growth inhibition. The
results are shown in Table 4.
Acknowledgements
Preventive activity against rice sheath blight by
submerged application
We are grateful to Dr. S. Sugai, the director of our
laboratories, and to Dr. T. Jojima, the former director,
for their encouragement throughout this work. We also
would like to thank Dr. K. Sato in our laboratories for
his helpful discussion.
Rice seedlings (variety Nipponbare) at the 3–4 leaf stage
were flooded to a depth of 1 cm with water in pots, and
then the test compound was applied to the water. After
keeping the seedlings in a greenhouse for 7 days, 4–5oat
grains cultured with R. solani were placed around the
base of each seedling. The seedlings were then kept in a
References and Notes
moist chamber (relative humidity: 100%) for 5days at
ꢀ
2
5–27 C. The number of grams per 10 acres required to
1. Itoh, H.; Yoneda, R.; Tobitsuka, J.; Matsuhisa, T.; Kajino,
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2
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