Synthesis and fungicidal activities of novel indene-substituted oxime ether strobilurins

Article abstract of DOI:10.1021/jf800273t

Nineteen novel indene-substituted oxime ether strobilurins, which used an indene group to stabilize the (E)-styryl group in SYP-Z071 (an unsaturated oxime strobilurin fungicide under development by the Shenyang Research Institute of Chemical Industry), were designed and synthesized. The biological assay results showed that all compounds possessed good or excellent fungicidal activities. It was found that most of the compounds showed higher fungicidal activities against Pyricularia oryzae, Phytophthora infestans, Erysiphe graminis, and Colletotrichum lagenarium than SYP-Z071 at the tested concentration. The biological assay results also indicated that most of the compounds exhibited higher in vivo fungicidal activities against cucumber Pseudoperonospora cubensis and C. lagenarium than the commercial fungicides trifloxystrobin and kresoxim-methyl at a concentration of 6.25 mg/L. Furthermore, it was found that α-(methoxyimino)-N-methylphenylacetamide oxime ethers 6m-s exhibited a broad spectrum and remarkably higher activities against all tested fungi. Especially, the 6-methylindene-substituted compound 6p was identified as the most promising candidate for further study.

Full text of DOI:10.1021/jf800273t

J. Agric. Food Chem. 2008, 56, 5247–5253 5247
Synthesis and Fungicidal Activities of Novel
Indene-Substituted Oxime Ether Strobilurins
SONG TU,*,† LONG-HE XU,‡ LI-YI YE,† XI WANG,† YONG SHA,† AND
†
ZONG-YUAN XIAO
Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical
Engineering, Xiamen University, Xiamen 361005, and Shenyang Research Institute of Chemical
Industry, Shenyang 110021, People’s Republic of China
Nineteen novel indene-substituted oxime ether strobilurins, which used an indene group to stabilize
the (E)-styryl group in SYP-Z071 (an unsaturated oxime strobilurin fungicide under development by
the Shenyang Research Institute of Chemical Industry), were designed and synthesized. The biological
assay results showed that all compounds possessed good or excellent fungicidal activities. It was
found that most of the compounds showed higher fungicidal activities against Pyricularia oryzae,
Phytophthora infestans, Erysiphe graminis, and Colletotrichum lagenarium than SYP-Z071 at the
tested concentration. The biological assay results also indicated that most of the compounds exhibited
higher in vivo fungicidal activities against cucumber Pseudoperonospora cubensis and C. lagenarium
than the commercial fungicides trifloxystrobin and kresoxim-methyl at a concentration of 6.25 mg/L.
Furthermore, it was found that R-(methoxyimino)-N-methylphenylacetamide oxime ethers 6m-s
exhibited a broad spectrum and remarkably higher activities against all tested fungi. Especially, the
6-methylindene-substituted compound 6p was identified as the most promising candidate for further
study.
KEYWORDS: Indene; oxime ether; strobilurins; fungicide; fungicidal activities
INTRODUCTION
oxime ether strobilurins were prepared, such as compounds d
and e (Figure 2). Compounds d, which were discovered by
Rohm and Hass Co. (the 4-Cl-substituted derivative of com-
pounds d is under development by Shenyang Research Institute
of Chemical Industry now and is named SYP-Z071 (17)),
contained an unsaturated oxime ether group and exhibited very
good fungicidal activities (18). It was also reported that
arylcyclopropyl oxime ether compounds e, which used a trans-
arylcyclopropyl group to displace the (E)-styryl group in
compounds d, also had excellent fungicidal activities (19).
In view of these facts, we have reported a series of novel
oxime ethers which used a benzopentatomic ring to stabilize
the (E)-styryl group in SYP-Z071 (16). Especially, it was found
that indene-substituted compounds possessed remarkable fun-
gicidal activities in this type of oxime ether strobilurins (16).
To study the structure-activity relationships of this type of
compound, a series of novel indene-substituted oxime ethers 6
were designed and synthesized in this study. The biological
assay results showed that all compounds exhibited good or
excellent fungicidal activities.
Strobilurins, which are naturally occurring derivatives of
ꢀ-methoxyacrylic acid, are an important class of agricultural
fungicides (1–4). However, it was clear that many natural
products themselves could not be used directly because of
insufficient levels of photochemical stability and volatility (2, 5).
The first two commercial strobilurin fungicides azoxystrobin
(ICI A 5504) and kresoxim-methyl (BAS 490 F) were discov-
ered by ICI and BASF from stilbene compound a, respectively,
by using a benzene ring as an aromatic bridge to stabilize the
triene system in strobilurin A (Figure 1) (2). Many synthetic
chemists also did much remarkable work on the synthetic
analogues of strobilurin A as fungicides, such as using a trans-
1,2-disubstituted cyclopropane group (6) and a cis-1,2-disub-
stituted cyclopentene group (5, 7) to stabilize the triene system
in strobilurin A to obtain analogues of strobilurin A (compounds
b and c (Figure 1)).
In recent years, oxime ether strobilurins have aroused the
interest of many synthetic and agricultural chemists since
trifloxystrobin (discovered by Novartis and sold to Bayer later)
was launched in 1999 (8–16). Subsequently, a series of active
MATERIALS AND METHODS
DMF was distilled and dried over 4 Å sieves. Other solvents and
reagents were obtained from commercial sources and used without
further purification. Silica gel (100-140 mesh) was used for column
chromatography. The intermediate (E)-methyl 2-(2-(bromomethyl)phe-
* To whom correspondence should be addressed. Fax: (86-592) 2183
054. E-mail: tusong_2001@hotmail.com.
† Xiamen University.
‡ Shenyang Research Institute of Chemical Industry.
10.1021/jf800273t CCC: $40.75  2008 American Chemical Society
Published on Web 06/12/2008

5248 J. Agric. Food Chem., Vol. 56, No. 13, 2008
Tu et al.
Figure 1. Structures of strobilurin A and its analogues.
Figure 2. Structures of trifloxystrobin and other oxime ether strobilurins.
nyl)-3-methoxyacrylate and (E)-methyl 2-(2-(bromomethyl)phenyl)-2-
(methoxyimino)acetate were provided by Shenyang Research Institute
of Chemical Industry. Melting points were determined with a Tech
X-6 micromelting point apparatus made in Beijing and are uncorrected.
The 1H NMR spectra were recorded in CDCl3 solution on a Varian
Mercury V × 300 NMR spectrophotometer with TMS as the internal
standard. A Perkin-Elmer 983 was used to determine the IR spectra.
Elemental analyses were performed on a Vario EL III elemental analysis
instrument, and the results were within 0.3% of the calculated
value.
chromatography (hexane/EtOAc ) 5/1) to afford the products 1-(1H-
inden-2-yl)ethanones 4. The yields of the products were 51.9-64.2%.
A mixture of the corresponding 1-(1H-inden-2-yl)ethanones 4 (3
mmol), hydroxylamine hydrochloride (4.5 mmol), NaOAc (4.5 mmol),
ethanol (10 mL), and H2O (10 mL) was heated for 2.5-5 h under reflux.
Then the reaction mixture was cooled to room temperature, poured
into 50 mL of hydrochloric acid (0.5 mol/L), and extracted with EtOAc.
The combined organic layers were dried over anhydrous MgSO4 and
concentrated under vacuum. The residue was purified by flash chro-
matography (hexane/EtOAc ) 4/1) to afford products 5a-g.
General Procedure for the Synthesis of Ortho-Halogenated
Benzaldehydes 3b, 3c, 3e, and 3g. A mixture of the corresponding
ortho-halogenated toluene 1 (4.8 mmol), acetic anhydride (6.9 g), acetic
acid (5.2 g), and concentrated sulfuric acid (2.8 g) was cooled to 0 °C
in an ice bath. Then an acetic acid (5.2 g) solution of CrO3 (1.8 g, 18
mmol) was dropped into the mixture over 1.5 h. Stirring of the mixture
was continued for 2 h at 0 °C. Then the reaction mixture was poured
into 120 mL of cold water and extracted with EtOAc. The com-
bined organic layers were dried over anhydrous MgSO4 and concen-
trated under vacuum. The residue (crude product 2) and concentrated
hydrochloric acid were heated for 2.5 h in dioxane under reflux. Then
the reaction mixture was extracted with EtOAc. The combined organic
layers were dried over anhydrous MgSO4 and concentrated under
vacuum. The residue was purified by flash chromatography (hexane/
EtOAc ) 10/1) to afford ortho-halogenated benzaldehydes 3b, 3c, 3e,
and 3g. The yields of the products were 74.3-86.3%.
General Procedure for the Synthesis of 1-(1H-Inden-2-yl)etha-
none Oximes 5a-g. The ortho-halogenated benzaldehyde 3 (3.0 mmol),
3-buten-2-ol (3.6 mmol), tetrabutylammonium chloride (TBAC) (6.0
mmol), NaOAc (7.5 mmol), LiCl (6.0 mmol), and Pd(OAc)2 (36 mg,
5 mol %) were added to a sealed flask. After the flask was evacuated
and purged with nitrogen, 30 mL of DMF was added to the flask via
syringe. Then the flask was placed in a 110 °C oil bath, and stirring
was continued for 1.5-4 h. The reaction mixture was extracted with
EtOAc. The combined organic layers were dried over anhydrous MgSO4
and concentrated under vacuum. The residue was purified by flash
Data for 1-(1H-Inden-2-yl)ethanone Oxime (5a). Straw yellow solid.
1
Yield: 89.7%. Mp: 175.8-177.5 °C. H NMR (CDCl3, 300 MHz): δ
2.25 (s, 3H, NdCCH3), 3.70 (s, 2H, CH2), 7.13 (s, 1H, CHdC),
7.23-7.28 (m, 2H, ArH), 7.39-7.46 (m, 2H, ArH). IR (KBr): ν
3200-3400 (br), 2390, 1635, 1010, 930, 850, 755, 715 cm-1
.
Data for 1-(6-Chloro-1H-inden-2-yl)ethanone Oxime (5b). White
solid. Yield: 83.6%. Mp: 179.2-180.6 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.19 (s, 3H, NdCCH3), 3.65 (s, 2H, CH2), 7.02 (d, J ) 7.2 Hz, 1H,
ArH), 7.15-7.25 (m, 1H, ArH), 7.28-7.35 (m, 1H, ArH), 7.39 (s, 1H,
CHdC). IR (KBr): ν 3425, 1630, 1420, 1370, 1020, 930, 875, 760
cm-1
.
Data for 1-(6-Fluoro-1H-inden-2-yl)ethanone Oxime (5c). White
solid. Yield: 77.8%. Mp: 171.6-173.6 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.20 (s, 3H, NdCCH3), 3.64 (s, 2H, CH2), 6.99-7.04 (m, 1H, ArH),
7.21-7.27 (m, 1H, ArH), 7.31-7.37 (m, 1H, ArH), 7.45-7.49 (m,
1H, ArH). IR (KBr): ν 3200-3400 (br), 2380, 1630, 1020, 940, 840,
760 cm-1
.
Data for 1-(6-Methyl-1H-inden-2-yl)ethanone Oxime (5d). White
solid. Yield: 86.3%. Mp: 181.8-183.5 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.23 (s, 3H, NdCCH3), 2.39 (s, 3H, ArCH3), 3.65 (s, 2H, CH2),
7.07-7.09 (m, 2H, ArH), 7.21-7.31 (m, 2H, ArH). IR (KBr): ν
3200-3400 (br), 1625, 1400, 1015, 925, 875, 820, 760 cm-1
.
Data for 1-(5-Chloro-1H-inden-2-yl)ethanone Oxime (5e). White
solid. Yield: 83.5%. Mp: 173.3-174.8 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.19 (s, 3H, NdCCH3), 3.65 (s, 2H, CH2), 7.02 (d, J ) 8.1 Hz, 1H,
ArH), 7.18-7.25 (m, 1H, ArH), 7.32-7.35 (m, 1H, ArH), 7.40-7.43

Indene-Substituted Oxime Ether Strobilurins
J. Agric. Food Chem., Vol. 56, No. 13, 2008 5249
(m, 1H, ArH). IR (KBr): ν 3430, 1630, 1420, 1365, 1015, 930, 870,
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(1H-inden-2-yl)-
ethylidene)amino)oxy)methyl]benzeneacetate (6f). Colorless viscous
liquid. Yield: 61.3%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s, 3H,
CH3CdN), 3.64 (s, 2H, CH2), 3.85 (s, 3H, COOCH3), 4.04 (s, 3H,
CdNOCH3), 5.09 (s, 2H, CH2O), 7.03 (s, 1H, CHdC), 7.19-7.25 (m,
3H, ArH), 7.35-7.43 (m, 4H, ArH), 7.48-7.51 (m, 1H, ArH). IR
(KBr): ν 2940, 1730, 1220, 1070, 1020, 760 cm-1. Anal. Calcd for
C22H22N2O4: C, 69.83; H, 5.86; N, 7.40. Found: C, 69.78; H, 5.95; N,
7.47.
815, 765 cm-1
.
Data for 1-(5-Fluoro-1H-inden-2-yl)ethanone Oxime (5f). White
solid. Yield: 97.8%. Mp: 168.7-169.8 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.16 (s, 3H, NdCCH3), 3.60 (s, 2H, CH2), 6.86-7.00 (m, 1H,
CHdC), 7.04-7.22 (m, 2H, ArH), 7.24-7.38 (m, 1H, ArH). IR (KBr):
ν 3420, 2960, 1635, 1475, 1380, 1220, 1005, 870 cm-1
.
Data for 1-(4-Chloro-1H-inden-2-yl)ethanone Oxime (5g). White
solid. Yield: 77.3%. Mp: 173.8-175.2 °C. 1H NMR (CDCl3, 300 MHz):
δ 2.18 (s, 3H, NdCCH3), 3.61 (s, 2H, CH2), 7.11-7.18 (m, 2H, ArH),
7.31-7.34 (m, 1H, ArH), 7.47 (s, 1H, CHdC). IR (KBr): ν 3200-3400
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(6-chloro-1H-inden-
2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6g). Colorless vis-
cous liquid. Yield: 64.5%. 1H NMR (CDCl3, 300 MHz): δ 2.10 (s,
3H, CH3CdN), 3.63 (s, 2H, CH2), 3.84 (s, 3H, COOCH3), 4.05 (s,
3H, CdNOCH3), 5.08 (s, 2H, CH2O), 7.10-7.15 (m, 1H, ArH),
7.17-7.24 (m, 2H, ArH), 7.30-7.42 (m, 4H, ArH), 7.48-7.51 (m,
1H, ArH). IR (KBr): ν 2960, 1725, 1220, 1080, 1020, 760 cm-1. Anal.
Calcd for C22H21ClN2O4: C, 64.00; H, 5.13; N, 6.79. Found: C, 64.12;
H, 5.22; N, 6.71.
(br), 2390, 1635, 1030, 960, 850, 760, 710 cm-1
.
General Procedure for the Synthesis of Methyl 3-Methoxypro-
penoate Oxime Ethers 6a-e and Methyl r-(Methoxyimino)ben-
zeneacetate Oxime Ethers 6f-l. A mixture of the corresponding
1-(1H-inden-2-yl)ethanoneoximes5(1.75mmol),(E)-methyl2-(2-(bromo-
methyl)phenyl)-3-methoxyacrylate or (E)-methyl 2-(2-(bromomethyl)-
phenyl)-2-(methoxyimino)acetate (1.75 mmol), and potassium carbonate
(3.5 mmol) were heated for 4-5 h in 10 mL of ethanol under reflux.
Then the reaction mixture was cooled to room temperature and extracted
with EtOAc. The combined organic layers were dried over anhydrous
MgSO4 and concentrated under vacuum. The residue was purified by
flash chromatography (hexane/EtOAc ) 10/1) to afford the products
methyl 3-methoxypropenoate oxime ethers 6a-e and methyl R-(meth-
oxyimino)benzeneacetate oxime ethers 6f-l.
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(6-fluoro-1H-inden-
2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6h). Straw yellow
viscous liquid. Yield: 58.7%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s,
3H, CH3CdN), 3.64 (s, 2H, CH2), 3.80 (s, 3H, COOCH3), 4.04 (s,
3H, CdNOCH3), 5.09 (s, 2H, CH2O), 7.12-7.16 (m, 1H, ArH),
7.18-7.24 (m, 2H, ArH), 7.31-7.43 (m, 4H, ArH), 7.48-7.51 (m,
1H, ArH). IR (KBr) ν 2960, 1730, 1220, 1080, 1260, 1020, 760 cm-1
.
Anal. Calcd for C22H21FN2O4: C, 66.66; H, 5.34; N, 7.07. Found: C,
66.62; H, 5.42; N, 7.17.
Data for Methyl (E,E)-3-Methoxy-2-[2-((((1-(6-chloro-1H-inden-2-
yl)ethylidene)amino)oxy)methyl)phenyl]propenoate (6a). Yellow viscous
liquid. Yield: 68.4%. 1H NMR (CDCl3, 300 MHz): δ 2.08 (s, 3H,
CH3CdN), 3.63 (s, 2H, CH2), 3.68 (s, 3H, CdCHOCH3), 3.80 (s, 3H,
COOCH3), 5.08 (s, 2H, CH2O), 7.11-7.15 (m, 1H, ArH), 7.17-7.21
(m, 1H, ArH), 7.28-7.41 (m, 5H, ArH), 7.48-7.51 (m, 1H, ArH),
7.58 (s, 1H, CdCHOCH3). IR (KBr): ν 2950, 1710, 1640, 1430, 1255,
1125, 1020, 760 cm-1. Anal. Calcd for C23H22ClNO4: C, 67.07; H,
5.38; N, 3.40. Found: C, 67.21; H, 5.59; N, 3.27.
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(6-methyl-1H-in-
den-2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6i). Yellow vis-
cous liquid. Yield: 71.5%. 1H NMR (CDCl3, 300 MHz): δ 2.10 (s,
3H, CH3CdN), 2.39 (s, 3H, ArCH3), 3.64 (s, 2H, CH2), 3.82 (s, 3H,
COOCH3), 4.04 (s, 3H, CdNOCH3), 5.10 (s, 2H, CH2O), 7.05-7.09
(m, 1H, ArH), 7.12-7.15 (m, 1H, ArH), 7.20-7.34 (m, 5H, ArH),
7.47-7.50 (m, 1H, ArH). IR (KBr): ν 2950, 1715, 1220, 1120, 1020,
760 cm-1. Anal. Calcd for C23H24N2O4: C, 70.39; H, 6.16; N, 7.14.
Found: C, 70.28; H, 6.11; N, 7.28.
Data for Methyl (E,E)-3-Methoxy-2-[2-((((1-(6-fluoro-1H-inden-2-
yl)ethylidene)amino)oxy)methyl)phenyl]propenoate (6b). Straw yellow
viscous liquid. Yield: 61.7%. 1H NMR (CDCl3, 300 MHz): δ 2.10 (s,
3H, CH3CdN), 3.64 (s, 2H, CH2), 3.69 (s, 3H, CdCHOCH3), 3.79 (s,
3H, COOCH3), 5.10 (s, 2H, CH2O), 7.12-7.16 (m, 1H, ArH),
7.18-7.21 (m, 1H, ArH), 7.32-7.46 (m, 5H, ArH), 7.49-7.53 (m,
1H, ArH), 7.59-7.62 (m, 1H, ArH). IR (KBr): ν 2960, 1715, 1630,
1430, 1260, 1020, 760 cm-1. Anal. Calcd for C23H22FNO4: C, 69.86;
H, 5.61; N, 3.54. Found: C, 69.67; H, 5.72; N, 3.29.
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(5-chloro-1H-inden-
2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6j). Straw yellow
viscous liquid. Yield: 64.5%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s,
3H, CH3CdN), 3.60 (s, 2H, CH2), 3.82 (s, 3H, COOCH3), 4.03 (s,
3H, CdNOCH3), 5.11 (s, 2H, CH2O), 7.10-7.14 (m, 1H, ArH),
7.18-7.34 (m, 5H, ArH), 7.39-7.42 (m, 1H, ArH), 7.47-7.50 (m,
1H, ArH). IR (KBr): ν 2950, 1725, 1230, 1120, 1020, 760 cm-1. Anal.
Calcd for C22H21ClN2O4: C, 64.00; H, 5.13; N, 6.79. Found: C, 64.09;
H, 5.12; N, 6.70.
Data for Methyl (E,E)-3-Methoxy-2-[2-((((1-(6-methyl-1H-inden-2-
yl)ethylidene)amino)oxy)methyl)phenyl]propenoate (6c). Yellow viscous
liquid. Yield: 71.0%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s, 3H,
CH3CdN), 2.39 (s, 3H, ArCH3), 3.64 (s, 2H, CH2), 3.68 (s, 3H,
CdCHOCH3), 3.81 (s, 3H, COOCH3), 5.10 (s, 2H, CH2O), 7.04-7.09
(m, 1H, ArH), 7.12-7.15 (m, 1H, ArH), 7.21-7.35 (m, 5H, ArH),
7.47-7.50 (m, 1H, ArH), 7.56 (s, 1H, CdCHOCH3). IR (KBr): ν 2950,
1715, 1630, 1420, 1120, 1020, 760 cm-1. Anal. Calcd for C24H25NO4:
C, 73.64; H, 6.44; N, 3.58. Found: C, 73.58; H, 6.46; N, 3.52.
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(5-fluoro-1H-inden-
2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6k). Yellow viscous
liquid. Yield: 57.8%. 1H NMR (CDCl3, 300 MHz): δ 2.42 (s, 3H,
CH3CdN), 3.62 (s, 2H, CH2), 3.81 (s, 3H, COOCH3), 4.04 (s, 3H,
CdNOCH3), 5.11 (s, 2H, CH2O), 7.03-7.15 (m, 1H, ArH), 7.28-7.34
(m, 4H, ArH), 7.45-7.47 (m, 1H, ArH), 7.49-7.51 (m, 1H, ArH),
7.93-7.95 (m 1H, ArH). IR (KBr): ν 2950, 1730, 1250, 1020, 870,
760 cm-1. Anal. Calcd for C22H21FN2O4: C, 66.66; H, 5.34; N, 7.07.
Found: C, 66.75; H, 5.44; N, 7.01.
Data for Methyl (E,E)-3-Methoxy-2-[2-((((1-(5-chloro-1H-inden-2-
yl)ethylidene)amino)oxy)methyl)phenyl]propenoate (6d). Yellow vis-
cous liquid. Yield: 66.3%. 1H NMR (CDCl3, 300 MHz): δ 2.13 (s,
3H, CH3CdN), 3.61 (s, 2H, CH2), 3.68 (s, 3H, CdCHOCH3), 3.81 (s,
3H, COOCH3), 5.10 (s, 2H, CH2O), 7.10-7.14 (m, 1H, ArH),
7.19-7.31 (m, 5H, ArH), 7.38-7.41 (m, 1H, ArH), 7.48-7.51 (m,
1H, ArH), 7.59 (s, 1H, CdCHOCH3). IR (KBr): ν 2950, 1710, 1635,
1460, 1250, 1120, 1020, 760 cm-1. Anal. Calcd for C23H22ClNO4: C,
67.07; H, 5.38; N, 3.40. Found: C, 67.23; H, 5.54; N, 3.29.
Data for Methyl (E,E)-R-(Methoxyimino)-2-[(((1-(4-chloro-1H-inden-
2-yl)ethylidene)amino)oxy)methyl]benzeneacetate (6l). Straw yellow
viscous liquid. Yield: 61.7%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s,
3H, CH3CdN), 3.62 (s, 2H, CH2), 3.81 (s, 3H, COOCH3), 4.05 (s,
3H, CdNOCH3), 5.11 (s, 2H, CH2O), 7.11-7.19 (m, 2H, ArH),
7.23-7.30 (m, 4H, ArH), 7.38-7.41 (m, 1H, ArH), 7.48-7.52 (m,
1H, ArH). IR (KBr): ν 2960, 1710, 1250, 1120, 1020, 760 cm-1. Anal.
Calcd for C22H21ClN2O4: C, 64.00; H, 5.13; N, 6.79. Found: C, 64.11;
H, 5.10; N, 6.68.
Data for Methyl (E,E)-3-Methoxy-2-[2-((((1-(4-chloro-1H-inden-2-
yl)ethylidene)amino)oxy)methyl)phenyl]propenoate (6e). Yellow viscous
liquid. Yield: 63.5%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s, 3H,
CH3CdN), 3.60 (s, 2H, CH2), 3.66 (s, 3H, CdCHOCH3), 3.80 (s, 3H,
COOCH3), 5.11 (s, 2H, CH2O), 7.10-7.19 (m, 2H, ArH), 7.22-7.29
(m, 4H, ArH), 7.38-7.41 (m, 1H, ArH), 7.48-7.51 (m, 1H, ArH),
7.59 (s, 1H, CdCHOCH3). IR (KBr): ν 2950, 1710, 1635, 1460, 1250,
1120, 1020, 760 cm-1. Anal. Calcd for C23H22ClNO4: C, 67.07; H,
5.38; N, 3.40. Found: C, 67.18; H, 5.46; N, 3.31.
General Procedure for the Synthesis of r-(Methoxyimino)-N-
methylphenylacetamide Oxime Ethers 6m-s. A mixture of the
corresponding methyl R-(methoxyimino)benzeneacetate oxime ethers
6f-l (0.5 mmol) and methylamine (0.37 g, 3 mmol, 25% in water)
was heated for 4-5 h in 5 mL of methanol under reflux. Then the
reaction mixture was cooled to room temperature and extracted with
EtOAc. The combined organic layers were dried over anhydrous MgSO4

5250 J. Agric. Food Chem., Vol. 56, No. 13, 2008
Tu et al.
Table 1. Fungicidal Activities of Compounds 6a-s (Inhibitory Ratio, %)
25 mg/mL testing concn
6.25 mg/mL testing concn
no.
R1
Cl
F
CH3
H
H
H
Cl
F
CH3
H
H
H
H
Cl
F
CH3
H
H
R2
R3
Z
Y
P. oryzae
B. cinerea
P. infestans
P. cubensis
E. graminis
C. lagenarium
6a
6b
6c
6d
6e
6f
6g
6 h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
H
H
H
Cl
H
H
H
H
H
Cl
F
H
H
H
H
H
Cl
F
H
H
H
H
Cl
H
H
H
H
H
H
Cl
H
H
H
H
H
H
Cl
CH
CH
CH
CH
CH
N
N
N
N
N
N
N
N
N
N
N
N
N
O
O
O
O
O
O
O
O
O
O
O
O
NH
NH
NH
NH
NH
NH
NH
50
100
100
50
100
100
100
100
100
100
100
100
100
50
100
100
100
100
100
80
80
50
80
80
80
80
80
50
80
80
80
100
100
100
80
100
100
80
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80
40
a
80
30
0
100
100
100
100
85
10
90
85
60
60
70
30
30
30
65
40
90
90
40
100
95
100
100
100
98
30
50
85
100
95
70
90
95
85
100
100
90
30
100
100
50
0
100
95
100
100
100
100
100
100
100
100
100
62.5
100
100
100
100
100
100
100
80
100
30
80
50
60
6s
SYP-Z071
trifloxystrobin
kresoxim-methyl
H
H
N
80
80
100
100
30
a The compound appeared to be phytotoxic.
and concentrated under vacuum. The residue was purified by flash
chromatography (hexane/EtOAc ) 1/1) to afford the products R-(meth-
oxyimino)-N-methylphenylacetamide oxime ethers 6m-s.
Anal. Calcd for C23H25N3O3: C, 70.57; H, 6.44; N, 10.73. Found: C,
70.63; H, 6.48; N, 10.68.
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(5-chloro-1H-
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6q). Yellow
viscous liquid. Yield: 86.6%. 1H NMR (CDCl3, 300 MHz): δ 2.11 (s,
3H, CH3CdN), 2.88 (d, J ) 4.8 Hz, 3H, CH3NH), 3.63 (s, 2H, CH2),
3.96 (s, 3H, CdNOCH3), 5.11 (s, 2H, CH2O), 7.10-7.14 (m, 1H, ArH),
7.17-7.34 (m, 5H, ArH), 7.38-7.41 (m, 1H, ArH), 7.47-7.50 (m,
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(1H-inden-2-
yl)ethylidene)amino)oxy)methyl]phenylacetamide (6m). Straw yellow
viscous liquid. Yield: 84.8%. 1H NMR (CDCl3, 300 MHz): δ 2.10 (s,
3H, CH3CdN), 2.88 (d, J ) 4.8 Hz, 3H, CH3NH), 3.63 (s, 2H, CH2),
3.94 (s, 3H, CdNOCH3), 5.08 (s, 2H, CH2O), 6.75 (br s, 1H, CH3NH),
7.00 (s, 1H, CHdC), 7.18-7.25 (m, 3H, ArH), 7.33-7.42 (m, 4H,
ArH), 7.47-7.50 (m, 1H, ArH). IR (KBr): ν 3360, 2940, 1670, 1520,
1030, 980, 760 cm-1. Anal. Calcd for C22H23N3O3: C, 70.01; H, 6.14;
N, 11.13. Found: C, 70.12; H, 6.26; N, 11.04.
1H, ArH). IR (KBr): ν 3360, 2950, 1670, 1510, 1040, 980, 760 cm-1
.
Anal. Calcd for C22H22ClN3O3: C, 64.15; H, 5.38; N, 10.20. Found: C,
64.24; H, 5.49; N, 10.13.
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(5-fluoro-1H-
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6r). Yellow
viscous liquid. Yield: 88.2%. 1H NMR (CDCl3, 300 MHz): δ 2.41 (s,
3H, CH3CdN), 2.88 (d, J ) 5.1 Hz, 3H, CH3NH), 3.62 (s, 2H, CH2),
3.96 (s, 3H, CdNOCH3), 5.11 (s, 2H, CH2O), 7.03-7.14 (m, 1H, ArH),
7.28-7.34 (m, 4H, ArH), 7.44-7.47 (m, 1H, ArH), 7.48-7.51 (m,
1H, ArH), 7.92-7.95 (m 1H, ArH). IR (KBr): ν 3360, 2960, 1675,
1520, 1040, 980, 760 cm-1. Anal. Calcd for C22H22FN3O3: C, 66.82;
H, 5.61; N, 10.63. Found: C, 66.91; H, 5.67; N, 10.47.
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(6-chloro-1H-
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6n). Yellow
viscous liquid. Yield: 84.5%. 1H NMR (CDCl3, 300 MHz): δ 2.09 (s,
3H, CH3CdN), 2.87 (d, J ) 5.1 Hz, 3H, CH3NH), 3.63 (s, 2H, CH2),
3.95 (s, 3H, CdNOCH3), 5.09 (s, 2H, CH2O), 7.10-7.15 (m, 1H, ArH),
7.17-7.24 (m, 2H, ArH), 7.30-7.41 (m, 4H, ArH), 7.48-7.51 (m,
1H, ArH). IR (KBr): ν 3360, 2960, 1670, 1520, 1020, 980, 760 cm-1
.
Anal. Calcd for C22H22ClN3O3: C, 64.15; H, 5.38; N, 10.20. Found: C,
64.28; H, 5.45; N, 10.11.
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(4-chloro-1H-
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(6-fluoro-1H-
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6o). Yellow
viscous liquid. Yield: 81.3%. 1H NMR (CDCl3, 300 MHz): δ 2.10 (s,
3H, CH3CdN), 2.85 (d, J ) 5.1 Hz, 3H, CH3NH), 3.64 (s, 2H, CH2),
3.96 (s, 3H, CdNOCH3), 5.10 (s, 2H, CH2O), 7.11-7.17 (m, 1H, ArH),
7.18-7.26 (m, 2H, ArH), 7.31-7.44 (m, 4H, ArH), 7.47-7.51 (m,
1H, ArH). IR (KBr): ν 3360, 2960, 1660, 1520, 1040, 760 cm-1. Anal.
Calcd for C22H22FN3O3: C, 66.82; H, 5.61; N, 10.63. Found: C, 66.78;
H, 5.65; N, 10.52.
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6s). Straw
1
yellow viscous liquid. Yield: 81.4%. H NMR (CDCl3, 300 MHz): δ
2.10 (s, 3H, CH3CdN), 2.87 (d, J ) 4.8 Hz, 3H, CH3NH), 3.62 (s,
2H, CH2), 3.97 (s, 3H, CdNOCH3), 5.10 (s, 2H, CH2O), 7.11-7.18
(m, 2H, ArH), 7.23-7.31 (m, 4H, ArH), 7.38-7.41 (m, 1H, ArH),
7.48-7.52 (m, 1H, ArH). IR (KBr): ν 3360, 2950, 1670, 1520, 1040,
980, 760 cm-1. Anal. Calcd for C22H22ClN3O3: C, 64.15; H, 5.38; N,
10.20. Found: C, 64.27; H, 5.45; N, 10.11.
Biological Assay. The fungicidal activities of compounds 6a-s
against Pyricularia oryzae, Botrytis cinerea, and Phytophthora infestans
in vitro were tested according to the following procedure (20): The
synthesized target compounds were dissolved in DMF to a concentration
of 250 mg/L. The solutions (1 mL) were mixed rapidly with thawed
potato glucose agar culture medium (9 mL) at 50 °C. The mixtures
were poured into Petri dishes. After the dishes were cooled to room
temperature, the solidified plates were incubated with a 4 mm mycelium
Data for (E,E)-R-(Methoxyimino)-N-methyl-2-[(((1-(6-methyl-1H-
inden-2-yl)ethylidene)amino)oxy)methyl]phenylacetamide (6p). Yellow
viscous liquid. Yield: 84.5%. 1H NMR (CDCl3, 300 MHz): δ 2.09 (s,
3H, CH3CdN), 2.87 (d, J ) 5.1 Hz, 3H, CH3NH), 3.63 (s, 2H, CH2),
3.95 (s, 3H, CdNOCH3), 5.09 (s, 2H, CH2O), 7.10-7.15 (m, 1H, ArH),
7.17-7.24 (m, 2H, ArH), 7.30-7.41 (m, 4H, ArH), 7.48-7.51 (m,
1H, ArH). IR (KBr): ν 3360, 2960, 1670, 1520, 1020, 980, 760 cm-1
.

Indene-Substituted Oxime Ether Strobilurins
J. Agric. Food Chem., Vol. 56, No. 13, 2008 5251
Scheme 1. General Synthetic Route for the Target Compounds 6a-s
disk at 28 °C for 48 h. Water was used as the blank control. The
mycelial elongation radius (mm) of the fungus settlements was
measured after 48 h of culture. The growth inhibition rates were
calculated with the following equation: I ) [(C - T)/C] × 100. Here,
I is the growth inhibition rate (%), C is the control settlement radius
(mm), and T is the treatment group fungus settlement radius (mm).
The fungicidal activities of compounds 6a-s against cucumber
Pseudoperonospora cubensis, wheat Erysiphe graminis, and cucumber
Colletotrichum lagenarium in vivo were tested according to the
following procedure (21): The synthesized target compounds (0.0111
g) were dissolved in 0.5 mL of DMF, and then distilled water
(containing 0.1% Tween 80) was added to the solution to a concentra-
tion of 1000 mg/L. The solution was diluted to the tested concentration,
sprayed onto the plants, and allowed to dry for 2 h. Twenty-four hours
later, the plants were inoculated with fungal spores. Each test utilized
control plants which were sprayed with a 1/1/2 (by volume) mixture
of acetone, methanol, and water (containing 0.1% Tween 80) and
inoculated with fungal spores. The results are percent disease control
as compared to that of the untreated check, wherein 100 is rated as
complete disease control and 0 as no disease control. The remainder
of the technique of each of the tests is as follows: (1) For cucumber P.
cubensis, large and fully expanded leaves were collected from the
cucumber plants which were maintained in the greenhouse. The cucum-
ber leaves were sprayed with the solution of the synthesized compound
and inoculated by a spore suspension of P. cubensis (1 × 105 spores/
mL of water) which was cultured on cucumber plants. The cucumber
leaves were returned to a controlled environmental chamber (T ) 20
°C, RH ) 90%) for 5 days. Then the leaves were examined for disease
development. (2) For wheat E. graminis, the fungal pathogen E.
graminis was cultured on wheat seedlings in a greenhouse conditions
(18 °C). 7-Day old wheat seedlings which had been previously sprayed
with the solution of the synthesized compound were inoculated by E.
graminis spores. The inoculated seedlings were kept in greenhouse
conditions (18 °C) and subirrigated. The percent disease control was
rated 7 days after the inoculation. (3) For cucumber C. lagenarium,
the fungal pathogen C. lagenarium was cultured on potato dextrose
agar (PAD) in the dark at 22 °C for a period of 8-14 days. Spores of
C. lagenarium were removed from the PAD plates. The spore
suspension of C. lagenarium (3 × 106 spores/mL of water) was sprayed
onto the upper leaf surface of 15 day old cucumber plants which had
been previously treated with the solution of the synthesized compound.
The plants were placed in a fluorescent-lighted mist chamber (12 h
light, 12 h dark) for 48 h. After that infection period, the plants were
placed in a growth chamber (T ) 25 °C, RH ) 80%) for 3 days. The
treated plants were then evaluated for disease control.
The results are listed in Table 1, in which the inhibition percentage
was expressed as the mean of values obtained in three independent
experiments. To make a judgment on the fungicidal potency of the
synthesized compounds, the developing unsaturated oxime ether
fungicide SYP-Z071 and two commercial fungicides, trifloxystrobin
and kresoxim-methyl, were used as standards.
RESULTS AND DISCUSSION
Synthetic Chemistry. The synthetic route for the target
compounds is outlined in Scheme 1. The key intermediates
2-acetylindenes 4 were prepared on the basis of previous
literature (16, 22). First, ortho-halogenated benzaldehydes 3 were
reacted with 3-buten-2-ol in the presence of 5% Pd(OAc)2, 2.5
equiv of NaOAc, 2 equiv of n-Bu4NCl (TBAC), and 2 equiv of
LiCl at 110 °C to give 2-acetylindenes 4 in good yields. Then

5252 J. Agric. Food Chem., Vol. 56, No. 13, 2008
Tu et al.
ACKNOWLEDGMENT
2-acetylindenes 4 were reacted with hydroxylamine hydrochlo-
ride to produce 1-(1H-inden-2-yl)ethanone oximes 5 in high
yield according to the method described previously (23, 24).
Subsequently, the target compounds methyl 3-methoxyprope-
noate oxime ethers 6a-e and methyl R-(methoxyimino)benze-
neacetate oxime ethers 6f-l were obtained by the reaction of
ethanone oximes 5 with (E)-methyl 2-(2-(bromomethyl)phenyl)-
3-methoxyacrylate or (E)-methyl 2-(2-(bromomethyl)phenyl)-
2-(methoxyimino)acetate in the presence of base according to
the literature (16, 25). The target compounds 6m-s were
produced by ammonolysis of the corresponding methyl R-(meth-
oxyimino)benzeneacetate oxime ethers 6f-l (11). The structures
of the desired compounds were confirmed by 1H NMR, IR, and
elemental analyses.
We thank the Pesticide Bioactivity Center of SYRICI
(Shenyang Research Institute of Chemical Industry) for the test
of biological activities.
LITERATURE CITED
(1) Beautement, K.; Clough, J. M.; De Fraine, P. J.; Godfrey, C. R. A.
Fungicidal ꢀ-methoxyacrylates: From natural products to novel
synthetic agricultural fungicides. Pestic. Sci. 1991, 31, 499–519.
(2) Sauter, H.; Steglich, W.; Anke, T. Strobilurins: Evolution of a
new class of active substances. Angew. Chem., Int. Ed. 1999, 38,
1328–1349, and references therein.
(3) Bartett, D. W.; Clough, J. M.; Godfrey, C. R. A.; Godwin, J. R.;
Hall, A. A.; Heaney, S. P.; Maund, S. J. Understanding the
strobilurin fungicides. Pestic. Outlook 2001, 12, 143–148.
(4) Bartlett, D. W.; Clough, J. M.; Godwin, J. R.; Hall, A. A.; Hamer,
M.; Parr-Dobrzanski, B. The strobilurin fungicides. Pest Manage.
Sci. 2002, 58, 649–662.
(5) Yue, X.; Qing, F.; Sun, H.; Fan, J. A Suzuki coupling approach
to double bonds locked analogues of strobilurin A. Tetrahedron
Lett. 1996, 37, 8213–8216.
(6) Rossi, R.; Carpita, A.; Ribecaia, A.; Mannina, L. Stereocontrolled
synthesis of carbon-carbon double bond locked analogues of
strobilurins which are characterized by a trans-1,2-disubstituted
cyclopropane ring. Tetrahedron 2001, 57, 2847–2856.
(7) Rossi, R.; Bellina, F.; Ciucci, D.; Carpita, A.; Fanelli, C. A new
synthesis of fungicidal methyl (E)-3-methoxypropenoates. Tet-
rahedron 1998, 54, 7595–7614.
(8) Ross, R.; Nguyen, D. V.; Shaber, S. H. Aryl and heteroarylcy-
clopropyl oxime ethers and their use as fungicides and insecticides.
EP 1024135, 2000; Chem. Abstr. 2000, 133, 135113z.
(9) Lim, H.; Chung, B. J.; Chung, J. S.; Choi, I. Y.; Park, D. J.;
Hwang, C. I. Novel acrylate-type fungicide. WO 0101779, 2001;
Chem. Abstr. 2001, 134, 82178m.
(10) Gewehr, M.; Sauter, H.; Muller, B.; Gypser, A.; Grammenos, W.;
Tormo, I. B. J.; Ptock, A.; Cullmann, O.; Grote, T.; Ammermann,
E.; Strathmann, S.; Lorenz, G.; Harries, V. Unsaturated oxime
ethers and the use thereof for control of harmful fungi and
veterinary pests. WO 0119803, 2001; Chem. Abstr. 2001, 134,
252341d.
(11) Ross, R.; Nguyen, D. V.; Shaber, S. H. Aryl and heteroarylcy-
clopropyl oxime ethers and their use as fungicides and insecticides.
EP 1120403, 2001; Chem. Abstr. 2001, 135, 137308g.
(12) Grote, T.; Ammermann, E.; Stierl, R.; Lorenz, G.; Strathmann,
S.; Schelberger, K.; Haden, E. Fungicide mixtures based on oxime
ether derivatives. WO 0249434, 2002; Chem. Abstr. 2002, 137,
29439h.
(13) Grote, T.; Ammermann, E.; Stierl, R.; Lorenz, G.; Stammler, G.;
Schelberger, K.; Haden, E. Fungicide mixtures on the basis of
oxime ether derivatives and guanidine derivatives. WO 03059067,
2003; Chem. Abstr. 2003, 139, 96697v.
Fungicidal Activities. The in vitro fungicidal activity results
of all compounds against P. oryzae, B. cinerea, and P. infestans
at a concentration of 25 mg/L are listed in Table 1. The results
of preliminary bioassays were compared with those of SYP-
Z071 and two commercial fungicides. As shown in Table 1,
all of the compounds 6a-s showed potent fungicidal activities
against the three tested fungi. Most of the compounds had more
potent fungicidal activities against P. oryzae and P. infestans
but a little lower activities against B. cinerea compared with
SYP-Z071. As compared with trifloxystrobin and kresoxim-
methyl, it was found that most of the compounds had similar
fungicidal activities against P. oryzae and P. infestans but
showed a little lower activities against B. cinerea.
The in vivo fungicidal activity results of all compounds
against cucumber P. cubensis, wheat E. graminis, and cucumber
C. lagenarium at a concentration of 6.25 mg/L are listed in
Table 1. As indicated in Table 1, most of the compounds
showed good fungicidal activities against the three tested fungi.
It was found that most of the compounds exhibited higher
fungicidal activities against wheat E. graminis and cucumber
C. lagenarium but lower activities against cucumber P. cubensis
than SYP-Z071. Additionally, it was found that 12 synthesized
compounds exhibited a 70% or more inhibition effect against
cucumber P. cubensis while trifloxystrobin and kresoxim-methyl
showed only a lower inhibition effect at the same test conditions.
On the other hand, most of the compounds showed similar
fungicidal activities against wheat E. graminis compared with
trifloxystrobin and kresoxim-methyl. It was also found that 13
compounds exhibited a 60% or more inhibition effect against
cucumber C. lagenarium while trifloxstrobin and kresoxim-
methyl showed 60% and 30% inhibition effects, respectively,
at the same test conditions. Analyzing all test results, it was
clear that R-(methoxyimino)-N-methylphenylacetamide oxime
ethers 6m-s exhibited broad spectra and remarkably higher
activities against all tested fungi. Furthermore, it can be
concluded that 6-methylindene-substituted compound 6p was
the most promising candidate for further study because it showed
a 100% inhibition effect against all tested fungi at the test
concentration.
(14) Aspinall, I. H.; Worthington, P. A. ꢀ-Methoxyacrylates; synthesis
of new types of strobilurin fungicides with extended side chains.
Pestic. Sci. 1999, 55, 197–198.
(15) Li, Y.; Zhang, H.-Q.; Liu, J.; Yang, X.-P.; Liu, Z.-J. Stereoselective
synthesis and antifungal activities of (E)-(methoxyimino) benze-
neacetate derivatives containing 1,3,5-substituted pyrazole ring.
J. Agric. Food Chem. 2006, 54, 3636–3640.
Conclusion. A series of new indene-substituted oxime ether
strobilurins 6 were designed and synthesized by modifying the
side chain of unsaturated oxime ether strobilurin fungicide SYP-
Z071. The biological assay results indicated that all compounds
exhibited good or excellent fungicidal activities. It was found
that R-(methoxyimino)-N-methylphenylacetamide oxime ethers
6m-s exhibited broad spectra and remarkably higher activities
against all tested fungi. Especially, 6-methylindene-substituted
compound 6p was identified as the most promising candidate
for further study. Further investigation of this type of compound
is also in progress now.
(16) Tu, S.; Xu, L.-H.; Yu, C.-R.; Zhang, H.; Li, Z.-N. Synthesis and
biological activities of novel oxime ethers. Chin. J. Org. Chem.
2007, 27, 228–234. (in Chinese)
(17) Zhang, L. X.; Li, Z. Ch.; Li, B.; Sun, K.; Zhang, Z. J.; Zhan,
F. K.; Wang, J.; Shaber, S. H. SYP-Z071: a new broad-
spectrum fungicide candidate. ProceedingssBCPC International
Congress: Crop Science & Technology, Glasgow, U.K, 2003; pp
93-98.
(18) Zhang, L.-X.; Li, Z.-C.; Li, Z.-N.; Zhang, H.; Liu, C.-L.; Li, B.;
Shaber, S. H. Unsaturated oxime ethers and their use as fungicides
and insecticides. EP 936213, 1999; Chem. Abstr. 1999, 131,
170174a.

Indene-Substituted Oxime Ether Strobilurins
J. Agric. Food Chem., Vol. 56, No. 13, 2008 5253
(19) Ross, R.; Shaber, S. H.; Nguyen, D. V. Aryl and heteroarylcy-
clopropyl oxime ethers and their use as fungicides and insecticides.
US 6063956, 2000; Chem. Abstr. 2000, 132, 334289r.
(20) Liu, J.-B.; Tao, W.-F.; Hu, Y.; Dai, H.; Fang, J.-X. Synthesis
and biological activities of 3-aryl-1-(pyridin-3-yl)-2-(1H-1,2,4-
triazol-1-yl)prop-2-en-1-ol. Chin. J. Org. Chem. 2006, 11, 1566–
1570.
(21) Hostettmann, K.; Harborne, J. B. In Methods in Plant Biochem-
istry; Dey, P. M., Ed.; Academic Press: London, 1991; Vol. 6,
pp 33-46.
derivatives as testosterone 5R- reductase inhibitor. Chem. Pharm.
Bull. 1999, 47, 226–240.
(24) Abele, E.; Lukevics, E. Recent advances in the chemistry oximes.
Org. Prep. Proced. Int. 2000, 32, 235–264.
(25) Waditschatka, R.; Kelsall, E.; Ziegler, H.; Wang, L. Process for
the preparation of strobilurin intermediates. WO 0034229, 2000;
Chem. Abstr. 2000, 133, 43384k.
¨
Received for review January 26, 2008. Revised manuscript received
March 14, 2008. Accepted March 18, 2008. We thank Shenyang BMD
Chemical Co., Ltd. for financial support of this investigation.
(22) Dayker, G.; Grundt, P. Aunulated ring-systems by domino-Heck-
aldol- condensation and domino-Heck-Michael-addition processes.
Tetrahedron Lett. 1996, 37, 619–622.
(23) Ishibashi, K.; Nakajima, K.; Sugioka, Y.; Sugiyama, M.; Hamada,
T.; Horikoshi, H.; Nishi, T. Synthesis of 2-phenylbenzofuran
JF800273T