November 2010
Synthesis, Structures, and Herbicidal Activity of Isoxazole Derivatives
1315
NMR (400 MHz, CDCl3) d: 7.50 (d, 1H, J ¼ 7.2 Hz, Ph),
7.36 (d, 1H, J ¼ 9.6 Hz, Ph), 3.3ꢁ3.9 (bd, 2H, CH2), 3.2 (br,
2H, CH2), 1.28 (m, 3H, CH3), 1.12 (m, 3H, CH3); MS (API-
ES, positive), m/z: 398.9 ([MþH]þ).
suiting for analysis was obtained by recrystallization with alco-
1
hol; mp 78.5ꢁ80.0ꢀC; IR (KBr): 1647 (C¼¼O) cmꢂ1; H NMR
(400 MHz, CDCl3) d: 7.54 (d, 1H, J ¼ 6.0 Hz, Ph), 7.28 (d,
1H, J ¼ 9.6 Hz, Ph), 7.12 (d, 1H, J ¼ 2.8 Hz, isoxazole), 4.82
(s, 2H OCH2CO), 3.3ꢁ3.5 (m, 4H, 2EtACH2), 1.26 (t, 3H, J
¼ 7.2 Hz, EtACH3), 1.13 (t, 3H, J ¼ 7.2 Hz, EtACH3); MS
(API-ES, positive), m/z: 416.9 ([MþNa]þ).
Anal. Calcd. for C15H12O2N2Cl2F4 (399.17): C, 45.14; H,
3.03; N, 7.02. Found: C, 45.13; H, 2.96; N, 6.91.
General procedure for the preparation of compound
8. To a slurry of 3-(4-chloro-2-fluoro-5-hydroxy)phenyl-5-tri-
fluoromethylisoxazole (3c) (1.5 g, 5 mmol), anhydrous potas-
sium carbonate (1.7 g, 25 mmol) in acetone (15 mL), was
added dimethyl sulfate (0.75 mL, 7.5 mmol) or corresponding
chlorides. The mixture reacted at room temperature or
refluxed, allowed to cool and poured into water, resulting in a
white solid precipitate.
Anal. Calcd. for C16H15O3N2ClF4 (394.7): C, 48.68; H,
3.83; N, 7.10. Found: C, 49.04; H, 3.59; N, 7.01.
3-[4-Chloro-2-fluoro-5-(20-methyl)allyl]phenyl-5-trifluorome-
thylisoxazole (8f). This compound was obtained as a white
solid (refluxed for 6 h), yield 88%. A sample suiting for analy-
sis was obtained by recrystallization with alcohol; mp
82.0ꢁ82.5ꢀC; 1H NMR (400 MHz, CDCl3) d: 7.54 (d, 1H, J
¼ 6.4 Hz, Ph), 7.28 (d, 1H, J ¼ 10.0 Hz, Ph), 7.15 (d, 1H, J
¼ 3.6 Hz, isoxazole), 5.18 (s, 1H, ¼¼CH), 5.05 (s, 1H, ¼¼CH),
4.55(s, 2H, OCH2), 1.87 (s, 3H, CH3); MS (API-ES, negative),
m/z: 333.9 ([M-H]ꢂ).
3-(4-Chloro-2-fluoro-5-methoxy)phenyl-5-trifluoromethylisox-
azole (8a). This compound was obtained as a white solid
(reacted at room temperature for 3 h), yield 89%. A sample
suiting for analysis was obtained by recrystallization with alco-
hol; mp 80.0ꢁ80.5ꢀC; 1H NMR (400 MHz, CDCl3) d: 7.54
(d, 1H, J ¼ 6.4 Hz, Ph), 7.28 (d, 1H, J ¼ 10.0 Hz, Ph), 7.15
(d, 1H, J ¼ 3.2 Hz, isoxazole), 3.96 (s, 3H, OCH3); MS (API-
ES, negative), m/z: 329.6 ([M þ Cl]ꢂ).
Anal. Calcd. for C14H10O2NClF4 (335.7): C, 50.09; H, 3.00;
N, 4.17. Found: C, 49.89; H, 2.90; N, 3.98.
Crystal structure determination. Saturated solution of 4a
and 4b in EtOAc were covered with n-hexane, and stand in air
at room temperature to give single crystals. The data were
obtained on a Bruker SMART APEX CCD diffractometer with
Anal. Calcd. for C11H6O2NClF4 (295.6): C, 44.69; H, 2.05;
N, 4.74. Found: C, 44.61; H, 2.00; N, 4.54.
˚
Ethyl 2-chloro-4-fluoro-5-[(5-trifluoromethyl)isoxazole-3-
yl]phenyl carbonate (8b). This compound was obtained as a
white solid (refluxed for 2 h), yield 96%. A sample suiting for
analysis was obtained by recrystallizationꢂw1 ith alcohol; mp
;
1H NMR (400
graphite monochromated Mo Ka radiation (k ¼ 0.71073 A).
Empirical absorption corrections were performed using the
SADABS program. Structures were solved by direct methods
and refined by full-matrix least-squares based on all data using
F2 using shelx97. All of the non-hydrogen atoms were refined
anisotropic ally. All of the hydrogen atoms were generated and
refined in ideal positions.
Post-emergence herbicidal activity test. Compounds were
formulated as 22 g/L emulsible concentrates, which were
diluted with water to the required concentration and applied to
pot-grown plants in a greenhouse.
Seeds of assayed weeds (Echinochloa crusgalli, Setaria viri-
dis, Abutilon theophrasti, and Acalypha australis) were germi-
nated in water at 30ꢀC under dark conditions for 48 h. The
germinated seeds were placed in a pot (0.1 m2) as 10 seeds
per-pot. While Echinochloa crusgalli was in the third-leaf
stage, Setaria viridis was in the second-leaf stage, Abutilon
theophrasti and Acalypha australis had two or three leaves,
the diluted formulation was applied. Fifteen days after treat-
ment, the upper-soil parts of the plants were cut off, and their
weights were measured freshly (FW). The degree of weeds
control by the test compounds was calculated with the follow-
ing formulation:
97.0ꢁ98.0ꢀC; IR (KBr): 1772 (C¼¼O) cm
MHz, CDCl3) d: 7.94 (d, 1H, J ¼ 7.2 Hz, Ph), 7.37 (d, 1H, J
¼ 10.0 Hz, Ph), 7.15 (d, 1H, J ¼ 2.4 Hz, isoxazole), 4.37 (q,
2H, J ¼ 7.2 Hz, CH2), 1.42 (t, 1H, J ¼ 7.2 Hz, CH3); MS
(API-ES, positive), m/z: 375.8 ([MþNa]þ).
Anal. Calcd. for C13H8O4NClF4 (353.7): C, 44.15; H, 2.28;
N, 3.96. Found: C, 44.43; H, 2.31; N, 3.87.
Methyl
20-[2-chloro-4-fluoro-5-[(5-trifluoromethyl)isoxa-
zole-3-yl]phenoxy]acetate (8c). This compound was obtained
as a white solid (refluxed for 2 h), yield 88%. A sample suit-
ing for analysis was obtained by recrystallizationꢂw1 ith alcohol;
;
1H NMR
mp 92.0ꢁ94.0ꢀC; IR (KBr): 1735 (C¼¼O) cm
(400 MHz, CDCl3) d: 7.50 (d, 1H, J ¼ 6.0 Hz, Ph), 7.32 (d,
1H, J ¼ 10.0 Hz, Ph), 7.15 (d, 1H, J ¼ 2.4 Hz, isoxazole),
4.78 (s, 2H, OCH2COO), 3.83 (s, 3H, CH3); MS (API-ES, pos-
itive), m/z: 375.8 ([MþNa]þ).
Anal. Calcd. for C13H8O4NClF4 (353.7): C, 44.15; H, 2.28;
N, 3.96. Found: C, 44.39; H, 2.38; N, 4.07.
Ethyl 20-[2-chloro-4-fluoro-5-[(5-trifluoromethyl)isoxazole-
3-yl]phenoxy]acetate (8d). This compound was obtained as a
white solid (refluxed for 2 h), yield 91%. A sample suiting for
analysis was obtained by recrystallizationꢂw1 ith alcohol; mp
CK ꢂ FW
Inhibition ¼
ꢄ 100%
72.5ꢁ73.0ꢀC; IR (KBr): 1729 (C¼¼O) cm
;
1H NMR (400
CK
MHz, CDCl3) d: 7.51(d, 1H, J ¼ 6.0 Hz, Ph), 7.32 (d, 1H, J
¼ 10.0 Hz, Ph), 7.15 (d, 1H, J ¼ 2.4 Hz, isoxazole), 4.76 (s,
2H, OCH2COO), 4.29 (q, 2H, J ¼ 7.2 Hz, Et-CH2), 1.32 (t,
3H, J ¼ 7.2 Hz, Et-CH3); MS (API-ES, positive), m/z: 368.0
([MþH]þ).
where CK is the fresh weight of untreated weed.
Each test was repeated three times.
Acknowledgments. The authors are grateful to the National
Natural Science Foundation of China (No. 20606005), the
Doctor Foundation of Liaoning Province, China (No.
20031068), and the Program for Changjiang Scholars and
Innovative Research Team in University (No. IRT0711) for fi-
nancial support of this work.
Anal. Calcd. for C14H10O4NClF4 (367.7): C, 45.73; H, 2.74;
N, 3.81. Found: C, 45.50; H, 2.66; N, 3.86.
N,N-diethyl 20-[2-chloro-4-fluoro-5-[(5-trifluoromethyl)isox-
azole-3-yl]phenoxy]acetamide (8e). This compound was ob-
tained as a white solid (refluxed for 2 h), yield 84%. A sample
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet