Synthesis and Antifungal Activities of New Type β-Methoxyacrylate-Based Strobilurin Analogues
2.42 (s, 3H, CH3), 7.01 (s, 1H, CH-Py), 7.25—7.28 (m,
1H, 3-ArH), 7.36—7.39 (m, 2H, 4,5-ArH), 7.56 (d, J=
8.0 Hz, 1H, 6-ArH); m/z (ESI): 271 (M+H)+.
CHOCH3), 3.58 (s, 3H, CO2CH3), 4.15 (d, J=8.0 Hz,
1H, CHCOOCH3), 4.15 (d, J=8.0 Hz, 1H, CHOCH3),
6.52 (s, 1H, CH-Py), 7.08 (d, J=8.0 Hz, 1H, 3'-ArH),
7.29—7.38 (m, 2H, 4',5'-ArH), 7.62 (d, J=4.0 Hz, 1H,
6'-ArH); ESI m/z: 399 (M+H)+, 421 (M+Na)+.
4,6-Dichloro-2-(m-tolylthio)pyrimidine
(4e)
Yield 62%, white solid; 1H NMR (400 MHz, CDCl3) δ:
2.40 (s, 3H, CH3), 7.02 (s, 1H, CH-Py), 7.27 (s, 1H,
2-ArH), 7.31 (t, J=12.0 Hz, 1H, 4-ArH), 7.38 (d, J=
12.0 Hz, 2H, 5,6-ArH); m/z (ESI): 271 (M+H)+, 282
(M+Na)+.
Methyl 2-(2-(6-chloro-2-(o-tolylthio)pyrimidin-4-
yloxy)phenyl)-3,3-dimethoxypropanoate (5d) yield
1
52%, White solid; H NMR (400 MHz, CDCl3) δ: 2.17
(s, 3H, CH3), 3.01 (s, 3H, CHOCH3), 3.33 (s, 3H, CHO-
CH3), 3.50 (s, 3H, CO2CH3), 4.02 (d, J=8.0 Hz, 1H,
CHCOOCH3), 4.83 (d, J=8.0 Hz, 1H, CHOCH3), 6.48
(s, 1H, CH-Py), 6.75 (d, J=8.0 Hz, 1H, 3'-ArH), 6.98—
7.00 (m, 1H, 5'-ArH), 7.02—7.06 (m, 2H, 3,5-ArH),
7.10 (t, J=8.0 Hz, 1H, 4'-ArH), 7.15 (t, J=8.0 Hz, 1H,
4-ArH), 7.32 (d, J=8.0 Hz, 1H, 6'-ArH), 7.42 (d, J=
8.0 Hz, 1H, 6-ArH); ESI m/z: 443 (M+H)+.
4,6-Dichloro-2-(p-tolylthio)pyrimidine (4f) Yield
1
79%, white solid; H NMR (400 MHz, CDCl3) δ: 2.41
(s, 3H, CH3), 7.01 (s, 1H, CH-Py), 7.23 (d, J=12.0 Hz,
2H, 2,6-ArH), 7.45 (d, J=12.0 Hz, 2H, 3,5-ArH); m/z
(ESI): 271 (M+H)+, 282 (M+Na)+.
4,6-Dichloro-2-(pyridin-2-ylthio)pyrimidine (4g)
Yield 61%, white solid; 1H NMR (400 MHz, CDCl3) δ:
7.01 (s, 1H, CH-Py), 7.26—7.27 (m, 1H, 4-PyH), 7.70
(d, J=4.0 Hz, 2H, 5,6-PyH), 8.58 (d, J=4.0 Hz, 1H,
3-PyH); m/z (ESI): 258 (M+H)+.
Methyl 2-(2-(6-chloro-2-(m-tolylthio)pyrimidin-4-
yloxy)phenyl)-3,3-dimethoxypropanoate (5e) Yield
1
61%, white solid; H NMR (400 MHz, CDCl3) δ: 2.25
(s, 3H, CH3), 3.08 (s, 3H, CHOCH3), 3.40 (s, 3H,
CHOCH3), 3.58 (s, 3H, CO2CH3), 4.08 (d, J=8.0 Hz,
1H, CHCOOCH3), 4.92 (d, J=8.0 Hz, 1H, CHOCH3),
6.57 (s, 1H, CH-Py), 6.85 (d, J=8.0 Hz, 1H, 3'-ArH),
7.07—7.14 (m, 2H, 4,5'-ArH), 7.16—7.23 (m, 4H,
2,5,4',6'-ArH), 7.51 (d, J=8.0 Hz, 1H, 6-ArH); m/z
(ESI): 443 (M+H)+; ESI m/z: 475 (M+H)+, 497 (M+
Na)+.
Methyl 2-(2-(6-chloro-2-(p-tolylthio)pyrimidin-4-
yloxy)phenyl)-3,3-dimethoxypropanoate (5f) Yield
57%, light yellow solid; 1H NMR (400 MHz, CDCl3) δ:
2.33 (s, 3H, CH3), 3.09 (s, 3H, CHOCH3), 3.40 (s, 3H,
CHOCH3), 3.57 (s, 3H, CO2CH3), 4.07 (d, J=8.0 Hz,
1H, CHCOOCH3), 4.91 (d, J=8.0 Hz, 1H, CHOCH3),
6.57 (s, 1H, CH-Py), 6.85 (d, J=8.0 Hz, 1H, 3'-ArH),
6.96 (d, J=12.0 Hz, 1H, 6'-ArH), 7.14 (d, J=8.0 Hz,
2H, 3,5-ArH), 7.20—7.24 (m, 2H, 4',5'-ArH), 7.51 (d,
J=12.0 Hz, 2H, 2,6-ArH); m/z (ESI): 443 (M+H)+;
ESI m/z: 475 (M+H)+, 497 (M+Na)+.
General procedure for the preparation of the com-
pounds 5a—5g
Compound 4 (2 mmol) was added to a solution of 3
(2 mmol) and anhydrous potassium carbonate (3 mmol)
in dry N,N-dimethylformamide (DMF) (10 mL). The
resulting solution was mixed and heated to 60 ℃ for 8
h. The reaction mixture was poured into cool H2O (30
mL) and was extracted with ethyl acetate (20 mL×3),
the combined ethyl acetate extracts were washed with
brine and followed by drying with anhydrous sodium
sulfate. The solvent was removed from the filtrate in
vacuo, the residue was purified by chromatography on a
silica gel column using a mixture of n-hexane and ethyl
acetate to afford 5.
Methyl 2-(2-(6-chloro-2-methylpyrimidin-4-yloxy)-
phenyl)-3,3-dimethoxypropanoate (5a) Yield 73%,
yellow solid; 1H NMR (400 MHz, CDCl3) δ: 2.58 (s,
3H, CH3), 3.18 (s, 3H, CHOCH3), 3.42 (s, 3H, CHO-
CH3), 3.59 (s, 3H, CO2CH3), 4.19 (d, J=8.0 Hz, 1H,
CHCOOCH3), 4.98 (d, J=8.0 Hz, 1H, CHOCH3), 6.59
(s, 1H, CH-Py), 7.09 (d, J=8.0 Hz, 1H, 3'-ArH), 7.31—
7.40 (m, 2H, 4',5'-ArH), 7.65 (d, J=8.0 Hz, 1H, 6'-ArH);
m/z (ESI): 367 (M+H)+, 389 (M+Na)+.
Methyl
2-(2-(6-chloro-2-(pyridin-2-ylthio)pyri-
midin-4-yloxy)phenyl)-3,3-dimethoxypropanoate (5g)
1
Yield 62%, light yellow solid; H NMR (400 MHz,
CDCl3) δ: 3.03 (s, 3H, CH3), 3.33 (s, 3H, CO2CH3),
3.47 (s, 3H,=CHOCH3), 3.98 (d, J=8.0 Hz, 1H,
CHCOOCH3), 4.85 (d, J=8.0 Hz, 1H, CHOCH3), 6.60
(s, 1H, CH-Py), 6.87 (d, J=8.0 Hz, 1H, ArH), 7.11—
7.14 (m, 3H, 4',5',6'-ArH), 7.25 (t, J=8.0 Hz, 1H,
4-PyH), 7.33 (t, J=12.0 Hz, 1H, 5-PyH), 7.48 (d, J=
8.0 Hz, 1H, 6-PyH), 8.36 (d, J=8.0 Hz, 1H, 3-PyH);
ESI m/z: 462 (M+H)+, 484 (M+Na)+.
Methyl 2-(2-(2,6-dichloropyrimidin-4-yloxy)phe-
nyl)-3,3-dimethoxypropanoate (5b) Yield 58%, yel-
1
low solid; H NMR (400 MHz, DMSO-d6) δ: 3.10 (s,
3H, CHOCH3), 3.32 (s, 3H, CHOCH3), 3.49 (s, 3H,
CO2CH3), 4.01 (d, J=8.0 Hz, 1H, CHCOOCH3), 5.00
(d, J=8.0 Hz, 1H, CHOCH3), 7.29 (d, J=8.0 Hz, 1H,
3'-ArH), 7.35—7.39 (m, 1H, 5'-ArH), 7.42—7.46 (m,
1H, 4'-ArH), 7.51 (s, 1H, CH-Py), 7.62 (d, J=8.0 Hz,
1H, 6'-ArH); ESI m/z: 387 (M+H)+, 409 (M+Na)+.
Methyl 2-(2-(6-chloro-2-(methylthio)pyrimidin-4-
yloxy)phenyl)-3,3-dimethoxypropanoate (5c) Yield
General procedure for the preparation of the com-
pounds 6a—6g
Methane sulphonic acid (0.05 mmol) was added to a
solution of 5 (1.5 mmol) in 10 mL of acetic anhydride.
The resulting solution was mixed and heated to 90 ℃
1
66%, white solid; H NMR (400 MHz, CDCl3) δ: 2.22
(s, 3H, SCH3), 3.16 (s, 3H, CHOCH3), 3.42 (s, 3H,
Chin. J. Chem. 2012, 30, 1517—1524
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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