New Type Oxazolidinone-Based Strobilurin Analogues
Bull. Korean Chem. Soc. 2010, Vol. 31, No. 11 3343
found C 48.57, H 2.88, N 11.33.
phenyl) oxazolidin-2-one (9a-9l):23 Amixture of compound 4
(3.0 mmol) and anhydrous K2CO3 (1.5 equiv., 0.63 g, 4.5 mmol)
in dry acetone (20 mL) was stirred and refluxed for 1 h. Then,
the solution 0.77 g (1.0 equiv, 3.0 mmol) of 8 in dry acetone
(20 mL) was added. The mixture was reacted for 12 h at the
refluxing temperature. The resulting mixture was cooled to room
temperature and filtered. The filtrate was added chloroform
(50 mL)and washed with water (2 × 50 mL). The organic layer
was dried over MgSO4, filtered and evaporated to afford re-
sidue which was purified by silica gel column chromatography
(eluent: petroleum ether/ethyl acetate = 2:1, v/v) monitoring
by TLC. The pure fractions were combined and evaporated to
afford the target compounds. The following compounds 9a-9l
were prepared according to this procedure.
3-(2-((1-Phenyl-2H-pyrazol-3-yloxy)methyl)phenyl)oxazo-
lidin-2-one (9a):Awhite solid, yield 88.5%, mp 105 - 106 oC,
1H-NMR (CDCl3) δ 4.00 (t, J = 7.8, 2H, CH2), 4,48 (t, J = 7.8,
2H, CH2), 5.37(s, 2H, CH2), 5.92(d, J = 2.6, 1H, CH), 7.19-
7.66 (m, 9H, Ar-H), 7.75 (d, J = 2.6, 1H, CH); 13C-NMR (CDCl3)
δ 48.77, 62.49, 67.72, 93.79, 117.84, 125.43, 126.81, 127.81,
128.36, 129.34, 129.47, 130.66, 134.98, 136.40, 140.07, 156.99,
164.03; MS m/z 336.1(M+) 176.0; Anal. calcd for C19H17N3O3:
C 68.05, H 5.11 N 12.53, found C 68.01, H 5.16, N 12.49.
3-(2-((1-(4-Chlorophenyl)-2H-pyrazol-3-yloxy)methyl)
phenyl)oxazolidin-2-one (9b): A white solid, yield 86%, mp
138 - 139 oC, 1H-NMR (CDCl3) δ 4.03 (t, J = 7.8, 2H, CH2), 4.47
(t, J = 7.8, 2H, CH2), 5.35 (s, 2H, CH2), 5.93 (d, J = 2.6, 1H, CH),
7.30-7.65 (m, 8H, Ar-H), 7.70 (d, J = 2.6, 1H, CH); 13C-NMR
(CDCl3) δ 48.83, 62.54, 67.84, 94.38, 118.98, 125.66, 126.83,
127.85, 128.44, 129.45, 129.58, 130.69, 134.87, 136.40, 140.88,
160.35, 164.2, MS m/z 370.1(M+), 176.0; Anal. calcd for C19H16-
ClN3O3: C 61.71, H 4.36, N 11.36, found C, 61.68, H, 4.40,
N,11.32.
3-(2-((1-(3-Chlorophenyl)-2H-pyrazol-3-yloxy)methyl)
phenyl)oxazolidin-2-one (9c): Awhite solid, yield 89.0%, mp
131 - 132 oC, 1H-NMR (CDCl3) δ 4.05 (t, J = 7.9, 2H, CH2),
4.50 (t, J = 7.9, 2H, CH2), 5.36 (s, 2H, CH2), 5.93 (d, J = 2.6,
1H, CH), 7.16-7.65(m, 8H, Ar-H), 7.71(d, J = 2.6, 1H, CH);
13C-NMR (CDCl3) δ 48.80, 62.55, 67.78, 94.72, 115.59, 118.09,
125.33, 126.73, 127.97, 128.41, 129.54, 130.43, 130.62, 134.84,
135.22, 136.39, 141.03, 164.22; MS m/z 370.0(M+), 176.0; Anal.
Calcd for C19H16ClN3O3: C 61.71, H 4.36, N 11.36, found C
61.68, H 4.40, N 11.31.
3-(2-((1-(4-Bromophenyl)-2H-pyrazol-3-yloxy)methyl)
phenyl)oxazolidin-2-one (9d): Awhite solid, yield 86.0%, mp
174 - 175 oC, 1H-NMR (CDCl3) δ 4.03 (t, J = 7.9, 2H, CH2), 4.48
(t, J = 7.9, 2H, CH2), 5.35 (s, 2H, CH2), 5.93 (d, J = 2.7, 1H,
CH), 7.29-7.65 (m, 8H, Ar-H), 7.70 (d, J = 2.7, 1H, CH); 13C-
NMR (CDCl3) δ, 48.83 62.54, 67.87, 94.50, 118.45, 119.32,
126.84, 127.85, 128.44, 129.59, 130.69, 132.42, 134.90, 136.44,
139.17, 157.01, 164.27; MS m/z 4.0(M+), 176.0; Anal. calcd for
C19H16BrN3O3: C 55.09, H 3.89, N 10.14, found C 55.06, H
3.93, N 10.10.
1-(3-Methylphenyl)-2H-pyrazolin-3-one (4l):Gray solid, mp
112 - 114 oC (decomposition), 1H-NMR (DMSO-d6) δ 2.35 (s,
3H, CH3), 5.79 (d, J = 2.2 Hz, 1H, CH), 7.00 (s, 1H, Ar-H),
7.29 (s, 1H, Ar-H), 7.48 (d, 2H, Ar-H), 8.18 (d, J = 2.2 Hz, 1H,
CH), 10.17 (s, 1H, OH); MS m/z 175.1 (M+); Anal. calcd for
C10H10N2O: C 68.95, H 5.79, N 16.08, found C 68.92, H 5.83,
N 16.07.
2-Chloroethyl-o-tolylcarbamate (6):20 Athree neck, 250 mL
round bottom flask fitted with a mechanical stirrer, dropping
funnel, and thermometer was charged with 2-methylaniline
(10.7 g, 0.1 mol), dichloromethane (150 mL) and 10% aqueous
NaOH solution (44 mL, 1.1 mol). 2-chloroethyl chloroformate
(10.8 mL, 0.11 mol) was added dropwise to the vigorously stirr-
ed reaction mixture over 20 min maintaining an internal tem-
o
perature of 25 C. At the end of the addition, the pH of the
aqueous layer was 8. After stirring an additional 15 min, the
pH of the aqueous layer (now 5 - 6) was adjusted to 11 with 5 mL
of 10% aqueous NaOH solution, and the mixture was stirred
an additional 4 h at refluxing temperature, monitored by TLC.
After cooling to room temperature, the organic layer washed
with water (200 mL× 3), dried over MgSO4, filtered and eva-
porated to afford residue. Yield 98%, white solid, mp 41 - 42 oC,
1H-NMR (CDCl3) δ 2.26 (s, 3H, CH3), 3.73 (t, J = 5.7 Hz, 2H,
CH2), 4.42 (t, J = 5.7 Hz, 2H, CH2), 6.47-7.23 (m, 4H, Ar-H),
7.74 (s, 1H, NH);MS m/z 214.1 (M+); Anal. calcd for C10H12-
ClNO2: C 55.95, H 6.10, N 6.52, found C 55.91, H 6.14, N 16.50.
3-(o-Tolyl)oxazolidin-2-one (7):21 A250 mL, 3 neck round
bottom flask fitted with a thermometer, mechanical stirrer, and
dropping funnel was charged with 78.1 g (0.344 mol) of com-
pound 6 and 200 mL of methanol. The white solution was treat-
ed with 82.5 mL of 25% methanolic NaOCH3, over 5 min main-
taining an internal temperature less than 30 oC. After 5 h the
reaction mixture was poured into water and extracted with
CH2Cl2 (3 × 300 mL). The combined organic extracts were
dried over MgSO4, filtered and evaporated to afford 62.8 g of
7 as a colorless oil. Yield 95.7%, 1H-NMR (CDCl3) δ 2.30 (s,
3H, CH3), 3.92 (t, J = 7.6 Hz, 2H, CH2), 4.49 (t, J = 7.6 Hz, 2H,
CH2), 7.22-7.27 (m, 4H, Ar-H);MS m/z 178.1 (M+); Anal. calcd
for C10H11NO2: C 67.40, H 6.79, N 7.86, found C 67.40, H 6.80,
N 7.85.
3-(2-(Bromomethyl)phenyl)oxazolidin-2-one (8):22 To the
solution of compound 7 (10.46 g, 59.0 mmol) in CCl4 (150 mL)
was added N-bromosuccinimide (1 equiv., 10.45 g, 59.0 mmol)
and azobisisobutyronitrile (0.1 equiv, 0.97 g, 5.9 mmol). The
reaction mixture was stirred and refluxed for 1 h without light
then filtered to remove succinimide and washed with brine
(100 mL × 3). The organic layer was dried over MgSO4, filtered
and evaporated to afford residue. The residue was purified by
silica gel column chromatography (eluent: petroleum ether/ethyl
acetate = 2:1, v/v) to afford 9.1 g of the title compound as a
white solid. Yield, 60%, mp 79 - 84oC, 1H-NMR (CDCl3) δ 4.10
(t, J = 7.9 Hz, 2H, CH2), 4.58 (t, J = 7.9 Hz, 2H, CH2), 4.58 (s,
2H, Ar-CH2Br), 7.23-7.47 (m, 4H, Ar-H);13C-NMR (CDCl3)
δ 30.01, 46.92, 63.17, 117.96, 129.78, 129.81, 131.93, 136.04,
136.26. MS m/z 256.0(M+), 146.1, 107.1; Anal. calcd for C10H10-
BrNO2: C 46.90, H 3.94, N 5.47, found C 46.87, H 3.96, N 5.43.
3-(2-((1-Substituted phenyl-2H-pyrazol-3-yloxy)methyl)
3-(2-((1-(3-Fluorophenyl)-2H-pyrazol-3-yloxy)methyl)
phenyl)oxazolidin-2-one (9e): Awhite solid, yield 81.0%, mp
91 - 93 oC, 1H-NMR (CDCl3) δ 4.00 (t, J = 7.9, 2H, CH2), 4.44
(t, J = 7.9, 2H, CH2), 5.35 (s, 2H, CH2), 5.91 (d, J = 2.6, 1H, CH),
6.85-7.63 (m, 8H, Ar-H), 7.71 (d, J = 2.6, 1H, CH);13C-NMR