PDS Inhibition by O-(2-Phenoxy)ethyl-N-aralkylcarbamates
J. Agric. Food Chem., Vol. 51, No. 10, 2003 3051
Table 1. Physical Data of O-(1-Ethyl-2-phenoxy)ethyl-N-benzylcarbamates and Their Phytoene Desaturase and ú-Carotene Desaturase Inhibitory
Activities
pI50
pI50
elem anal. found
[calcd] (%)
no.
R
mp (°C)
60−61
(PDS)
(ZDS)
1H NMR (δ, DMSO)
1
1
3-CF
6.9
7.1
7.0
<4.0
<4.0
<4.0
0.90 (3H, t, JH ) 7.4 Hz), 1.64 (2H, m), 4.04 (2H, d, JH ) 6.3 Hz), 4.18 (2H, d, JH )
6.1 Hz), 4.91 (1H, m), 6.88−6.97 (3H, m), 7.01−7.32 (6H, m), 7.78 (1H, t, JH ) 6.2 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.66 (2H, m), 4.01 (2H, d, JH ) 5.1 Hz), 4.19 (2H, d, JH )
6.2 Hz), 4.90 (1H, m), 6.90−6.95 (3H, m), 7.18−7.33 (7H, m), 7.78 (1H, t, JH ) 6.2 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.70 (2H, m), 4.09 (2H, d, JH ) 10.5 Hz), 4.18 (2H, d, JH )
6.5 Hz), 4.92 (1H, m), 6.94 (1H, t, JH ) 7.6 Hz), 7.14−7.31 (7H, m), 7.41 (1H, d, JH )
7.9 Hz), 7.78 (1H, t, JH ) 6.2 Hz)
0.90 (3H, t, JH ) 7.4 Hz), 1.64 (2H, m), 4.04 (2H, d, JH ) 6.3 Hz), 4.18 (2H, d, JH )
6.1 Hz), 4.91 (1H, m), 6.88−6.97 (3H, m), 7.01−7.32 (6H, m), 7.78 (1H, t, JH ) 6.2 Hz)
0.89 (3H, t, JH ) 7.4 Hz), 1.63 (2H, m), 4.03 (2H, m), 4.17 (2H, d, JH ) 6.2 Hz),
4.88 (1H, m), 6.94 (2H, d, JH ) 8.9 Hz), 7.20−7.32 (7H, m), 7.77 (1H, t, JH ) 6.2 Hz)
0.90 (3H, t, JH ) 7.4 Hz), 1.64 (2H, m), 3.99−4.19 (4H, m), 4.89 (1H, m), 6.72−6.84 (3H, m),
7.20−7.34 (6H, m), 7.78 (1H, t, JH ) 6.1 Hz)
0.90 (3H, t, JH ) 7.4 Hz), 1.65 (2H, m), 4.06 (2H, m), 4.18 (2H, d, JH ) 6.1 Hz), 4.89 (1H, m),
6.94 (2H, d, JH ) 8.1 Hz), 7.10−7.32 (7H, m), 7.77 (1H, t, JH ) 6.2 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.66 (2H, m), 4.05−4.19 (4H, m), 4.92 (1H, m), 7.20−7.33 (6H, m),
7.38−7.51 (3H, m), 7.77 (1H, t, JH ) 6.2 Hz)
0.92 (3H, t, JH ) 7.4 Hz), 1.67 (2H, m), 4.12−4.26(4H, m), 4.92 (1H, m), 7.20−7.27 (5H, m),
7.40 (1H, dd, JH ) 2.1 and 8.1 Hz), 7.56 (1H, t, JH ) 8.2 Hz), 7.71−7.83 (3H, m)
0.90 (3H, t, JH ) 7.5 Hz), 1.66 (2H, m), 2.26 (3H, s), 3.98 (2H, m), 4.19 (2H, d, JH ) 6.2 Hz),
4.89 (1H, m), 6.70−6.75 (3H, m), 7.11−7.33 (6H, m), 7.78 (1H, t, JH ) 6.2 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.17 (6H, d, JH ) 6.9 Hz), 1.65 (2H, m), 2.83 (1H, m), 4.01 (2H, m),
4.19 (2H, d, JH ) 6.2 Hz), 4.88 (1H, m), 6.71−6.82 (3H, m), 7.14−7.32 (6H, m),
7.77 (1H, t, JH ) 6.1 Hz)
0.90 (3H, t, JH ) 7.3 Hz), 1.65 (2H, m), 3.71 (3H, s), 4.02 (2H, m), 4.18 (2H, d, JH ) 6.1 Hz),
4.88 (1H, m), 6.48−6.51 (3H, m), 7.12−7.32 (6H, m), 7.77 (1H, t, JH ) 5.9 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.31 (3H, t, JH ) 7.1 Hz), 1.67 (2H, m), 4.03−4.20 (4H, m),
4.30 (2H, q, JH ) 7.1 Hz), 4.91 (1H, m), 7.18−7.22 (6H, m), 7.39−7.46 (2H, m),
7.54 (1H, m), 7.76 (1H, t, JH ) 6.1 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.46 (2H, m), 4.00−4.19 (4H, m), 4.91 (1H, m), 7.16−7.43 (8H, m),
7.53 (1H, d, JH ) 7.7 Hz), 7.77 (1H, t, JH ) 6.2 Hz), 13.02 (1H, br)
0.91 (3H, t, JH ) 7.4 Hz), 1.65 (2H, m), 2.02 (3H, s), 3.99 (2H, m), 4.19 (2H, d, JH ) 6.1 Hz),
6.60 (1H, d, JH ) 8.0 Hz), 7.05−7.32 (8H, m), 7.77 (1H, t, JH ) 6.0 Hz), 9.90 (1H, br)
0.91 (3H, t, JH ) 7.4 Hz), 1.69 (2H, m), 4.08−4.26 (4H, m), 4.92 (1H, m), 7.15−7.33 (8H, m),
7.77 (1H, t, JH ) 6.0 Hz)
0.91 (3H, t, JH ) 7.4 Hz), 1.69 (2H, m), 4.05−4.26 (4H, m), 4.92 (1H, m), 7.18−7.36 (7H, m),
7.55 (1H, d, JH ) 2.5 Hz), 7.78 (1H, t, JH ) 6.1 Hz)
C, 62.22; H, 5.38; N, 3.75
[C, 62.12; H, 5.49; N, 3.81]
C, 72.79; H, 7.32; N, 4.13
[C, 72.22; H, 7.07; N, 4.68]
C, 64.75; H, 6.03; N, 4.20
[C, 64.77; H, 6.04; N, 4.20]
3
2
3
H
62−63
71−72
2-Cl
4
3-Cl
4-Cl
3-F
60−61
81−82
63−64
67−68
90−91
76−77
75−76
56−57
7.3
5.5
7.2
7.1
7.3
7.1
6.9
6.9
<4.0
<4.0
<4.0
<4.0
<4.0
<4.0
<4.0
<4.0
C, 64.80; H, 5.95; N, 4.10
[C, 64.77; H, 6.04; N, 4.20]
C, 64.73; H, 6.16; N, 3.97
[C, 64.77; H, 6.04; N, 4.20]
C, 68.00; H, 6.42; N, 4.25
[C, 68.12; H, 6.35; N, 4.41]
C, 57.20; H, 5.50; N, 3.40
[C, 57.15; H, 5.33; N, 3.70]
C, 70.31; H, 6.17; N, 8.65
[C, 70.35; H, 6.21; N, 8.64]
C, 64.74; H, 5.82; N, 7.83
[C, 62.78; H, 5.85; N, 8.13]
C, 72.73; H, 7.50; N, 4.28
[C, 72.82; H, 7.40; N, 4.47]
C, 73.85; H, 7.87; N, 3.85
[C, 73.87; H, 7.97; N, 4.10]
5
6
7
3-Br
8
3-CN
3-NO
9
2
10
11
3-CH
3
3-C H -iso
3
7
12
13
3-OCH
48−49
6.8
6.9
<4.0
<4.0
C, 69.16; H, 7.12; N, 4.00
[C, 69.28; H, 7.04; N, 4.25]
C, 67.70; H, 6.71; N, 3.46
[C, 67.91; H, 6.78; N, 3.77]
3
3-COOC H
oil
2
5
14
15
16
17
18
19
20
3-COOH
3-NHCOCH
170−172
139−140
104−105
72−73
<5.0
5.4
<4.0
<4.0
<4.0
<4.0
<4.0
<4.0
<4.0
C, 66.36; H, 6.12; N, 3.92
[C, 66.46; H, 6.16; N, 4.08]
C, 67.29; H, 6.69; N, 7.70
[C, 67.40; H, 6.79; N, 7.86]
C, 58.62; H, 5.27; N, 3.50
[C, 58.71; H, 5.20; N, 3.80]
C, 58.60; H, 5.28; N, 3.58
[C, 58.71; H, 5.20; N, 3.80]
C, 58.60; H, 5.28; N, 3.58
[C, 58.71; H, 5.20; N, 3.80]
C, 58.67; H, 5.05; N, 3.80
[C, 58.71; H, 5.20; N, 3.80]
C, 58.68; H, 5.48; N, 3.52
[C, 58.71; H, 5.20; N, 3.80]
3
2,3-Cl2
2,4-Cl2
2,5-Cl2
2,6-Cl2
3,4-Cl2
6.9
5.3
90−91
5.4
0.91 (3H, t, JH ) 7.4 Hz), 1.67 (2H, m), 4.08−4.26 (4H, m), 4.93 (1H, m), 7.02 (1H, dd, JH )
1.8 and 8.5 Hz), 7.09−7.31 (6H, m), 7.44 (1H, d, JH ) 8.3 Hz), 7.77 (1H, t, JH ) 6.1 Hz)
0.94 (3H, t, JH ) 7.4 Hz), 1.73 (2H, m), 4.02−4.27 (4H, m), 4.87 (1H, m), 7.13−7.32 (6H, m),
7.47 (1H, d, JH ) 8.1 Hz), 7.78 (1H, t, JH ) 6.1 Hz)
99−100
58−59
<5.0
6.5
0.90 (3H, t, JH ) 7.4 Hz), 1.63 (2H, m), 4.08 (2H, m), 4.18 (2H, d, JH ) 6.2 Hz), 4.89 (1H, m),
6.95 (1H, dd, JH ) 2.9 and 8.9 Hz), 7.20−7.33 (6H, m), 7.50 (1H, t, JH ) 8.9 Hz),
7.77 (1H, d, JH ) 6.2 Hz)
21
3,5-Cl2
88−89
6.5
<4.0
0.90 (3H, t, JH ) 7.4 Hz), 1.63 (2H, m), 4.04−4.24 (4H, m), 4.88 (1H, m), 7.00−7.33 (8H, m),
C, 58.74; H, 5.51; N, 3.49
[C, 58.71; H, 5.20; N, 3.80]
7.77 (1H, t, JH ) 6.1 Hz)
norflurazon
flurtamone
flurochloridone
SAN 380H
7.5
6.7
6.1
5.1
<4.0
<4.0
<4.0
4.3
to diphosgene (3.6 g, 31 mmol) at 0 °C and stirred for 3 h at 0-25 °C.
The reaction mixture was filtered, and the filtrate was concentrated
under reduced pressure. [2-(3-Chlorophenoxy)-1-ethyl]ethyl chlorofor-
mate was obtained in quantitative yield. The product could be used in
the subsequent reaction without further purification. To the chlorofor-
mate was added a solution of benzylamine (3.3 g, 30 mmol) and
pyridine (2.5 g, 31 mmol) in tetrahydrofuran (20 mL) at 5 °C. The
reaction mixture was stirred for 24 h at room temperature. After
evaporation, the residue was flash-chromatographed on silca gel with
ethyl acetate/petroleum ether (1:10, v/v). The isolated compound was
further purified by recrystallization from a mixture of dichloromethane
(M+, 100%), 206 (M+ - C6H4ClO). Anal. Calcd for C18H20ClNO3: C,
64.77; H, 6.04; N, 4.20. Found: C, 64.80; H, 5.95; N, 4.05.
[2-(3-Chlorophenoxy)-1-ethyl]ethyl benzoate (41). Benzoyl chloride
(700 mg, 5 mmol) in tetrahydrofuran (10 mL) was added to a solution
of [2-(3-chlorophenoxy)-1-ethyl]ethanol (800 mg, 4 mmol) and tri-
ethylamine (500 mg, 5 mmol) in tetrahydrofuran (10 mL). The reaction
mixture was stirred for 5 h at 5-25 °C and heated for 30 min at 40
°C. After evaporation of the reaction mixture, ethyl acetate (50 mL)
was added. The solution was washed with NaCl solution (3 × 50 mL).
The organic phase was dried over anhydrous sodium sulfate and then
concentrated to a syrup. The desired compound was separated using
flash chromatography on silica gel with ethyl acetate/petroleum ether
(1:15, v/v): yield, 740 mg (61%); oil; 1H NMR (250 MHz, DMSO) δ
0.94 (3H, t, JH ) 7.4 Hz), 1.80 (2H, m), 4.24 (2H, d, JH ) 5.0 Hz),
5.29 (1H, m), 6.89-6.99 (2H, m), 7.06 (1H, t, JH ) 2.2 Hz), 7.27 (1H,
t, JH ) 8.1 Hz), 7.51 (2H, t, JH ) 7.7 Hz), 7.65 (1H, t, JH ) 7.4 Hz),
7.94 (2H, d, JH ) 7.0 Hz); MS (EI), m/z 306 (M + 2, 32.5%), 304
(M+, 100%), 177 (M+ - C6H4ClO). Anal. Calcd for C17H17ClO3: C,
67.00; H, 5.62. Found: C, 66.92; H, 5.67.
1
and petroleum ether: yield, 7.0 g (70%); solid; mp, 60-61 °C; H
NMR (250 MHz, DMSO) δ 0.91 (3H, t, JH ) 7.4 Hz), 1.70 (2H, m),
4.09 (2H, d, JH ) 10.5 Hz), 4.18 (2H, d, JH ) 6.5 Hz), 4.92 (1H, m),
6.94 (1H, t, JH ) 7.6 Hz), 7.14-7.31 (7H, m), 7.41 (1H, d, JH ) 7.9
Hz), 7.78 (1H, t, JH ) 6.2 Hz); 13C NMR (62.5 MHz, DMSO) δ 9.56
(1C, s), 24.03 (1C, s), 45.06 (1C, s), 68.99 (1C, s), 73.84 (1C, s),
113.03-115.16 (5C, m), 127.13-128.64 (5C, m), 121.13 (1C, s),
138.40 (1C, s), 159.45 (1C, s); MS (EI), m/z 335 (M + 2, 32.5%), 333