Article
J. Agric. Food Chem., Vol. 58, No. 5, 2010 2737
compounds were obtained by the reaction of heptafluoroisopropyl aniline
with benzoyl isocyanates at room temperature in dried ethyl acetate (16).
General Procedure for the Synthesis of Heptafluoroisopropyl
Aniline Derivatives I. Heptafluoroisopropyl iodide (1.3 mmol), tetra-
butylammonium bromide (TBAB, 0.1 mmol), sodium bicarbonate
(1.3 mmol), and sodium hydrosulfite (1.3 mmol) were added sequentially
to a mixture of the arylamine (1 mmol) in diethyl ether and water. The
mixture was stirred at room temperature until TLC monitoring showed
that the reaction was complete (typically ca. 8-10 h). The mixture was
diluted in water and extracted with ethyl acetate. The organic layer was
washed successively with 2 N hydrochloric acid, 5% sodium carbonate,
and a saturated salt solution, dried over anhydrous MgSO4, and concen-
trated in vacuum, and the yellow crude product was purified by column
chromatography on silica gel using a petroleum ether/ethyl acetate (4:1)
mixture as eluent to afford the pure heptafluoroisopropylaniline.
General Procedure for the Synthesis of Target Compounds
IIa-n. A solution of aroyl isocyanate (3 mmol) in 2 mL of dried ethyl
acetate was added to a solution of 3 mmol heptafluoroisopropylaniline in
2 mL of dried ethyl acetate. After 5-7 h of stirring at room temperature,
the mixture was filtered and washed with a small amount of petroleum
ether and dried in a vacuum desiccator to give the desired compound
without further purification.
N-(2,6-Difluorobenzoyl)-N0-(4-heptafluoroisopropylphenyl)urea IIa:
yield, 85%; white solid; mp 213.5-215.9 °C; 1H NMR (400 MHz, CDCl3)
δ 7.06 (2H, t, J=8.4 Hz, ArH), 7.57 (3H, d, J=8.8 Hz, ArH), 7.66 (2H, d,
J=8.4 Hz, ArH), 8.92 (1H, s, NH), 10.63 (1H, s, NH); 13C NMR (100
MHz, CDCl3) δ 112.6, 120.3, 122.4, 126.6, 133.9, 139.4, 150.4, 158.8,
161.4, 162.1. HRMS Calcd for C17H9F9N2O2 (Mþ): 444.0520. Found:
444.0520.
N-(2,6-Difluorobenzoyl)-N0-(2-chloro-4-heptafluoroisopropylphenyl)urea
IIb: yield, 80%; white solid; mp 191.2-193.5 °C; 1H NMR (400 MHz,
CDCl3) δ 7.09 (2H, t, J=8.8 Hz, ArH), 7.54 (2H, t, J=7.2 Hz, ArH), 7.69
(1H, s, ArH), 8.19 (1H, s, NH), 8.53 (1H, d, J=8.8 Hz, ArH), 11.16 (1H, s,
NH); 13C NMR(100 MHz, CDCl3) δ 112.5, 121.7, 123.8, 124.9, 127.4,
129.8, 133.7, 134.4, 150.2, 161.5. HRMS Calcd for C17H8F9Cl N2O2 (Mþ):
478.0131. Found: 478.0131.
112.5, 118.8, 120.7, 123.1, 127.6, 130.1, 133.9, 151.1, 158.6, 161.2, 162.5.
HRMS Calcd for C17H8BrF9N2O2 (Mþ): 521.9625. Found: 521.9625.
N-(2,6-Difluorobenzoyl)-N0-(3-methyl-4-heptafluoroisopropylphenyl)urea
IId: yield, 84%; white solid; mp 180.7-182.8 °C; 1H NMR (400 MHz,
CDCl3) δ 2.46 (3H, s, CH3), 7.04 (2H, t, J=8.0 Hz, ArH), 7.37 (1H, d, J=
8.8 Hz, ArH), 7.45 (1H, s, ArH), 7.49-7.56 (1H, m, ArH), 8.05 (1H, d, J=
8.8 Hz, ArH), 9.64 (1H, s, NH), 10.62 (1H, s, NH); 13C NMR (100 MHz,
CDCl3) δ 18.2, 112.4, 119.2, 120.9, 121.9, 122.2, 124.1, 127.4, 128.3, 133.5,
138.0, 151.0, 158.7, 161.2, 162.4. HRMS Calcd for C18H11F9N2O2 (Mþ):
458.0677. Found: 458.0677.
N-(2,6-Difluorobenzoyl)-N0-(2-heptafluoroisopropyl-4-methylphenyl)urea
IIe: yield, 81%; white solid; mp 177.6-178.6 °C; 1H NMR (400 MHz,
CDCl3) δ 2.41 (3H, s, CH3), 7.01 (2H, t, J=8.4 Hz, ArH), 7.32 (2H, t, J=
8.4 Hz, ArH), 7.45-7.52 (1H, m, ArH), 7.75 (1H, s, ArH), 9.02 (1H, s,
NH), 10.60 (1H, s, NH); 13C NMR (100 MHz, CDCl3) δ 21.0, 112.2, 112.3,
127.4, 132.5, 151.4, 158.7, 161.2, 161.8. HRMS Calcd for C18H11F9N2O2
(Mþ): 458.0678. Found: 458.0677.
N-(2,6-Difluorobenzoyl)-N0-(2-heptafluoroisopropyl-4-methoxylphenyl)-
urea IIf: yield, 85%; white solid; mp 173.9-175.6 °C; 1H NMR (400
MHz, CDCl3) δ 3.85 (3H, s, OCH3), 6.96-7.03 (3H, m, ArH), 7.09 (1H,
s, ArH), 7.42-7.49 (1H, m, ArH), 7.66 (1H, s, ArH), 9.32 (1H, s, NH),
10.44 (1H, s, NH); 13C NMR (100 MHz, CDCl3) δ 55.6, 112.1, 112.3,
116.4, 121.9, 133.2, 151.8, 158.7, 161.2, 161.9. HRMS Calcd for
C18H11F9N2O3 (Mþ) 474.0612. Found: 474.0626.
N-(2,6-Difluorobenzoyl)-N0-(3-chloro-4-heptafluoroisopropylphenyl)urea
IIg: yield, 75%; white solid; mp 197.9-199.0 °C; 1H NMR (400 MHz,
CDCl3) δ 7.08 (2H, t, J=8.4 Hz, ArH), 7.43 (1H, d, J=8.8 Hz, ArH),
7.52-7.59 (2H, m, ArH), 7.82 (1H, s, ArH), 9.31 (1H, s, NH), 10.72 (1H, s,
NH); 13C NMR (100 MHz, CDCl3) δ 111.8, 112.6, 118.0, 123.9, 134.1,
140.0, 150.7, 158.7, 161.3, 162.4. HRMS Calcd for C17H8F9Cl N2O2 (Mþ):
478.0131. Found: 478.0131.
N-(2,6-Difluorobenzoyl)-N0-(2-heptafluoroisopropyl-4-bromophenyl)urea
IIh: yield, 79%; white solid; mp 161.7-163.1 °C; 1H NMR (400 MHz,
CDCl3) δ 6.98-7.03 (2H, m, ArH), 7.46-7.58 (1H, m, ArH), 7.60 (2H, d, J
=8.0 Hz, ArH), 7.83 (1H, s, ArH), 9.41 (1H, s, NH), 10.80 (1H, s, NH);
13C NMR (100 MHz, CDCl3) δ 111.9, 112.3, 118.8, 119.1, 121.7, 122.0,
130.0, 133.4, 133.7, 134.6, 151.3, 158.7, 161.2, 161.9. HRMS Calcd for
C17H8 BrF9N2O2 (Mþ): 521.9625. Found: 521.9625.
N-(2,6-Difluorobenzoyl)-N0-(2,6-dimethyl-4-heptafluoroisopropylphenyl)-
urea IIi: yield, 95%; white solid; mp 203.6-206.7 °C; 1H NMR (400
MHz, CDCl3) δ 2.38 (6H, s, CH3), 7.20 (3H, t, J=8.4 Hz, ArH), 7.34 (2H,
s, ArH), 8.78 (1H, s, NH), 9.85 (1H, s, NH); 13C NMR (100 MHz, CDCl3)
δ 18.8, 111.9, 112.6, 125.4, 133.7, 135.7, 136.4, 150.5, 158.8, 161.4, 162.0.
HRMS Calcd for C19H13F9N2O2(Mþ): 472.0832. Found: 472.0833.
N-(2,6-Difluorobenzoyl)-N0-(2-fluoro-4-heptafluoroisopropylphenyl)urea
IIj: yield, 85%; white solid; mp 199.8-202.0 °C; 1H NMR (400 MHz,
CDCl3) δ 7.06 (2H, t, J=8.8 Hz, ArH), 7.35 (1H, d, J=8.8 Hz, ArH), 7.42
(1H, d, J=11.2 Hz, ArH), 7.55 (1H, s, ArH), 8.29 (1H, s, ArH), 9.11(1H, s,
NH), 10.91(1H, s, NH); 13C NMR (100 MHz, CDCl3) δ 111.6, 112.7,
113.2, 121.7, 122.1, 128.4, 133.9, 134.0, 151.1, 153.5, 158.9, 161.4, 161.9;
MS (EI, 70 ev) m/z (%)=462 (Mþ, 30), 141 (100).
N-(2,6-Difluorobenzoyl)-N0-(3-bromo-4-heptafluoroisopropylphenyl)urea
IIc: yield, 80%; white solid; mp 183.7-185.3 °C; 1H NMR (400 MHz,
CDCl3) δ 7.07 (2H, t, J=8.4 Hz, ArH), 7.17 (1H, t, J=8.0 Hz, ArH), 7.26
(1H, t, J=7.2 Hz, ArH), 7.51-7.58 (1H, m, ArH), 7.77 (1H, s, ArH), 9.93
(1H, s, NH), 10.57 (1H, s, NH); 13C NMR (100 MHz, CDCl3) δ 112.2,
N-(2,6-Difluorobenzoyl)-N0-(2,6-difluoro-4-heptafluoroisopropylphenyl)-
urea IIk: yield, 80%; white solid; mp: 197.3-198.9; 1H NMR (400 MHz,
CDCl3) δ 7.02 (2H, t, J=8.8 Hz, ArH), 7.27 (1H, d, J=8.0 Hz, ArH), 7.36
(1H, d, J=5.2 Hz, ArH), 7.47-7.52 (1H, m, ArH), 9.20(1H, s, NH), 10.05
(1H, s, NH); 13C NMR (100 MHz, CDCl3) δ 110.1, 111.7, 112.6, 115.9,
116.2, 128.5, 133.8, 134.0, 150.4, 156.4, 158.9, 161.4, 162.1. HRMS Calcd
for C17H7F11N2O2 (Mþ): 480.0332. Found: 480.0332.
Figure 1. Structure of flubendiamide.
Scheme 1. General Synthetic Route for the Target Compounds