Journal of Agricultural and Food Chemistry
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d6) δ 2.48 (s, 3H, S−CH3), 7.26−7.33 (m, 2H, Ph−H, Py−H), 7.41 (dt,
1H, J = 7.6, 1.4 Hz, Ph−H), 7.57 (dd, 1H, J = 8.0, 1.4 Hz, Ph−H), 7.63
(dd, 1H, J = 7.9, 1.3 Hz, Ph−H), 8.00 (dd, 1H, J = 7.1, 1.6 Hz, Py−H),
8.62 (dd, 1H, J = 4.8, 1.7 Hz, Py−H), 10.22 (s, 1H, CONH); MS (ESI),
278.03 (C13H11ClN2OS, [M + H]+). Anal. Calcd for C13H11ClN2OS: C,
56.01; H, 3.98; N, 10.05. Found: C, 55.73; H, 3.75; N, 10.26.
N-(2-Bromophenyl)-2-(methylthio)nicotinamide 3a-04: yellow
powder; yield, 88.7%; mp, 142−143 °C; 1H NMR (400 MHz,
DMSO-d6) δ 2.51 (s, 3H, S−CH3), 7.23−7.30 (m, 2H, Ph−H, Py−
H), 7.41 (dt, 1H, J = 7.6, 1.3 Hz, Ph−H), 7.57 (dd, 1H, J = 7.9, 1.3 Hz,
Ph−H), 7.73 (dd, 1H, J = 8.0, 1.3 Hz, Ph−H), 8.01 (dd, 1H, J = 7.6, 1.4
Hz, Py−H), 8.62 (dd, 1H, J = 4.8, 1.7 Hz, Py−H), 10.19 (s, 1H,
CONH); MS (ESI), 322.98 (C13H11BrN2OS, [M + H]+). Anal. Calcd
for C13H11BrN2OS: C, 48.31; H, 3.43; N, 8.67. Found: C, 48.36; H, 3.75;
N, 8.30.
2-(Methylthio)-N-(o-tolyl)nicotinamide 3a-05: white powder; yield,
42.1%; mp, 197−198 °C; 1H NMR (400 MHz, DMSO-d6) δ 2.29 (s, 3H,
Ar−CH3), 2.49 (s, 3H, S−CH3), 7.16−7.28 (m, 4H, 3Ph−H, Py−H),
7.39 (d, 1H, J = 7.3 Hz, Ph−H), 7.95 (d, 1H, J = 7.1 Hz, Py−H), 8.60
(dd, 1H, J = 4.8, 1.6 Hz, Py−H), 9.99 (s, 1H, CONH); MS (ESI), 259.08
(C14H14N2OS, [M + H]+). Anal. Calcd for C14H14N2OS: C, 65.09; H,
5.46; N, 10.84. Found: C, 65.18; H, 5.93; N, 10.47.
Anal. Calcd for C13H11FN2OS: C, 59.53; H, 4.23; N, 10.68. Found: C,
59.41; H, 4.29; N, 10.10.
N-(3-Bromophenyl)-2-(methylthio)nicotinamide 3a-12: light yel-
1
low powder; yield, 82.0%; mp, 168−169 °C; H NMR (400 MHz,
DMSO-d6) δ 2.49 (s, 3H, S−CH3), 7.28 (dd, 1H, J = 7.5, 4.8 Hz, Py−H),
7.33−7.35 (m, 2H, Ph−H), 7.63−7.66 (m, 1H, Ph−H), 7.94 (dd, 1H, J
= 7.6, 1.7 Hz, Ph−H), 8.05−8.06 (m, 1H, Py−H), 8.61 (dd, 1H, J = 4.9,
1.7 Hz, Py−H), 10.63 (s, 1H, CONH); MS (ESI), 322.98
(C13H11BrN2OS, [M + H]+). Anal. Calcd for C13H11BrN2OS: C,
48.31; H, 3.43; N, 8.67. Found: C, 48.26; H, 3.71; N, 8.60.
2-(Methylthio)-N-(3-(trifluoromethyl)phenyl)nicotinamide 3a-13:
1
white powder; yield, 82.0%; mp, 168−169 °C; H NMR (400 MHz,
DMSO-d6) δ 2.49 (s, 3H, S−CH3), 7.31 (dd, 1H, J = 7.0, 4.0 Hz, Py−H),
7.36−7.38 (m, H, Ph−H), 7.74 (dd, 1H, J = 8.4, 2.0 Hz, Ph−H), 7.79
(dd, 1H, J = 8.2, 2.0 Hz, Ph−H), 7.91 (dd, 1H, J = 7.6, 1.8 Hz, Ph−H),
8.12 (dd, 1H, J = 8.6, 3.4 Hz, Py−H), 8.61 (dd, 1H, J = 6.0, 1.6 Hz, Py−
H), 10.38 (s, 1H, CONH); MS (ESI), 313.05 (C14H11F3N2OS, [M +
H]+). Anal. Calcd for C14H11F3N2OS: C, 53.84; H, 3.55; N, 8.97. Found:
C, 53.91; H, 3.67; N, 9.01.
2-(Methylthio)-N-(3-nitrophenyl)nicotinamide 3a-14: yellow pow-
der; yield, 75.2%; mp, 198−199 °C; 1H NMR (400 MHz, DMSO-d6) δ
2.49 (s, 3H, S−CH3), 7.31 (dd, 1H, J = 7.6, 4.8 Hz, Py−H), 7.68 (t, 1H, J
= 8.2 Hz, Ph−H), 8.00−8.02 (m, 2H, Ph−H), 8.06 (dd, 1H, J = 8.2, 1.0
Hz, Ph−H), 8.64 (dd, 1H, J = 4.9, 1.7 Hz, Py−H), 8.75 (t, 1H, J = 2.0 Hz,
Py−H), 10.95 (s, 1H, CONH); MS (ESI), 290.05 (C14H11F3N2OS, [M
+ H]+). Anal. Calcd for C13H11N3O3S: C, 53.97; H, 3.83; N, 14.52.
Found: C, 53.99; H, 3.50; N, 14.65.
N-(3-Methoxyphenyl)-2-(methylthio)nicotinamide 3a-15: white
powder; yield, 90.1%; mp, 165−166 °C; 1H NMR (400 MHz,
DMSO-d6) δ 2.48 (s, 3H, S−CH3), 3.76 (s, 3H, Ar−OCH3), 6.70−
6.73 (m, H, Ph−H), 7.25−7.28 (m, 3H, 2Ph−H, Py−H), 7.40 (s, H,
Ph−H), 7.90 (dd, 1H, J = 7.6, 1.7 Hz, Py−H), 8.06 (dd, 1H, J = 8.2, 1.0
Hz, Py−H), 8.60 (dd, 1H, J = 4.9, 1.7 Hz, Py−H), 10.45 (s, 1H,
CONH); MS (ESI), 290.05 (C14H14N2O2S, [M + H]+). Anal. Calcd for
C14H14N2O2S: C, 53.97; H, 3.83; N, 14.52. Found: C, 53.99; H, 3.50; N,
14.65.
2-(Methylthio)-N-(2-(trifluoromethyl)phenyl)nicotinamide 3a-06:
1
white crystal; yield, 60.3%; mp, 164−165 °C; H NMR (400 MHz,
DMSO-d6) δ 2.48 (s, 3H, S−CH3), 7.30 (dd, 1H, J = 7.6, 4.8 Hz, Py−H),
7.55−7.59 (m, 2H, Ph−H), 7.76−7.79 (m, 1H, Ph−H), 7.82 (d, 1H, J =
7.9 Hz, Ph−H), 7.92 (dd, 1H, J = 7.6, 1.6 Hz, Py−H), 8.62 (dd, 1H, J =
4.8, 1.7 Hz, Py−H), 10.31 (s, 1H, CONH); MS (ESI), 313.05
(C14H11F3N2OS, [M + H]+). Anal. Calcd for C14H11F3N2OS: C, 53.84;
H, 3.55; N, 8.97. Found: C, 53.51; H, 3.24; N, 8.64.
N-(2,4-Dichlorophenyl)-2-(methylthio)nicotinamide 3a-07: light
1
yellow powder; yield, 51.7%; mp, 183−184 °C; H NMR (400 MHz,
DMSO-d6) δ 2.48 (s, 3H, S−CH3), 7.20−7.24 (m, 1H, Ph−H), 7.28
(dd, 1H, J = 7.6, 4.8 Hz, Py−H), 7.43 (dd, 1H, J = 8.6, 1.9 Hz, Ph−H),
7.63−7.73 (m, 1H, Ph−H), 8.00 (d, 1H, J = 7.6 Hz, Py−H), 8.63 (dd,
1H, J = 4.8, 1.7 Hz, Py−H), 10.31 (s, 1H, CONH); MS (ESI), 312.99
(C13H10Cl2N2OS, [M + H]+). Anal. Calcd for C13H10Cl2N2OS: C,
49.85; H, 3.22; N, 8.94. Found: C, 49.33; H, 3.10; N, 8.54.
N-(3,4-Dichlorophenyl)-2-(methylthio)nicotinamide 3a-16: white
crystal; yield, 88.4%; mp, 151−152 °C; 1H NMR (400 MHz, DMSO-d6)
δ 2.49 (s, 3H, S−CH3), 7.29 (dd, 1H, J = 7.6, 4.9 Hz, Py−H), 7.64 (s,
2H, Ph−H), 7.96 (dd, 1H, J = 7.6, 1.7 Hz, Ph−H), 8.09 (s, 2H, Py−H),
8.62 (dd, 1H, J = 4.9, 1.5 Hz, Py−H), 10.75 (s, 1H, CONH); MS (ESI),
290.05 (C13H10Cl2N2OS, [M + H]+). Anal. Calcd for C13H10Cl2N2OS:
C, 53.97; H, 3.83; N, 14.52. Found: C, 53.99; H, 3.50; N, 14.65.
N-(3-Chloro-4-fluorophenyl)-2-(methylthio)nicotinamide 3a-17:
N-(2,6-Difluorophenyl)-2-(methylthio)nicotinamide 3a-08: white
powder; yield, 56.1%; mp, 191−192 °C; 1H NMR (400 MHz, DMSO-
d6) δ 2.47 (s, 3H, S−CH3), 7.28 (dd, 1H, J = 7.6, 4.8 Hz, Py−H), 7.50
(dd, 1H, J = 8.6, 2.3 Hz, Ph−H), 7.66 (d, 1H, J = 8.6 Hz, Ph−H), 7.75 (d,
1H, J = 2.4 Hz, Ph−H), 8.00 (dd, 1H, J = 7.6, 1.6 Hz, Py−H), 8.62 (dd,
1H, J = 4.8, 1.6 Hz, Py−H), 10.29 (s, 1H, CONH); MS (ESI), 281.05
(C13H10F2N2OS, [M + H]+). Anal. Calcd for C13H10F2N2OS: C, 55.71;
H, 3.60; N, 9.99. Found: C, 55.03; H, 3.38; N, 9.62.
1
white powder; yield, 82.0%; mp, 160−161 °C; H NMR (400 MHz,
DMSO-d6) δ 2.49 (s, 3H, S−CH3), 7.28 (dd, 1H, J = 7.6, 4.8 Hz, Py−H),
7.45 (t, 1H, J = 9.1 Hz, Ph−H), 7.60−7.65 (m, 1H, Ph−H), 7.94 (dd,
1H, J = 7.6, 1.7 Hz, Ph−H), 8.02 (dd, 1H, J = 6.9, 2.5 Hz, Py−H), 8.62
(dd, 1H, J = 4.8, 1.7 Hz, Py−H), 10.68 (s, 1H, CONH); MS (ESI),
297.02 (C13H10ClFN2OS, [M + H]+). Anal. Calcd for C13H10ClFN2OS:
C, 52.62; H, 3.40; N, 9.44. Found: C, 52.87; H, 3.53; N, 9.65.
2-(Methylthio)-N-(2,4,5-trichlorophenyl)nicotinamide 3a-09:
1
white powder; yield, 72.8%; mp, 183−184 °C; H NMR (400 MHz,
DMSO-d6) δ 2.43 (s, 3H, S−CH3), 7.24 (dd, 1H, J = 7.8, 4.8 Hz, Py−H),
7.67 (dd, 1H, J = 8.2, 3.6 Hz, Ph−H), 8.21−8.23 (m, 2H, Ph−H, Py−
H), 8.66 (dd, 1H, J = 4.8, 1.8 Hz, Py−H); MS (ESI), 346.95
(C13H9Cl3N2OS, [M + H]+). Anal. Calcd for C13H10F2N2OS: C, 44.92;
H, 2.61; N, 8.06. Found: C, 45.02; H, 2.41; N, 8.07.
N-(4-Chloro-3-fluorophenyl)-2-(methylthio)nicotinamide 3a-18:
1
white powder; yield, 82.7%; mp, 150−151 °C; H NMR (400 MHz,
CDCl3) δ 2.48 (s, 3H, S−CH3), 7.28 (dd, 1H, J = 7.6, 4.9 Hz, Py−H),
7.49 (dd, 1H, J = 8.9, 1.8 Hz, Ph−H), 7.58 (t, 1H, J = 8.6 Hz, Ph−H),
7.86 (dd, 1H, J = 11.9, 2.3 Hz, Ph−H), 7.94 (dd, 1H, J = 7.6, 1.6 Hz, Py−
H), 8.62 (dd, 1H, J = 4.8, 0.9 Hz, Py−H), 10.78 (s, 1H, CONH); MS
(ESI), 397.02 (C23H40N2OS, [M + H]+). Anal. Calcd for C23H40N2OS:
C, 54.62; H, 3.40; N, 9.44. Found: C, 57.47; H, 3.62; N, 9.48.
N-(2,5-Dimethoxyphenyl)-2-(methylthio)nicotinamide 3a-10:
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white−gray powder; yield, 58.2%; mp, 189−190 °C; H NMR (400
MHz, DMSO-d6) δ 2.48 (s, 3H, S−CH3), 3.73 (s, 3H, Ar−OCH3), 3.78
(s, 3H, Ar−OCH3), 6.74 (dd, 1H, J = 9.0, 3.0 Hz, Ph−H), 7.01 (d, 1H, J
= 9.0 Hz, Ph−H), 7.24 (dd, 1H, J = 7.5, 4.9 Hz, Py−H), 7.60 (s, 1H, Ph−
H), 7.91 (d, 1H, J = 7.1 Hz, Py−H), 8.58 (dd, 1H, J = 4.8, 1.6 Hz, Py−
H), 9.59 (s, 1H, CONH); MS (ESI), 305.09 (C15H16N2O3S, [M + H]+).
Anal. Calcd for C15H16N2O3S: C, 59.19; H, 5.30; N, 9.20. Found: C,
59.69; H, 5.70; N, 9.01.
N-(3,5-Bis(trifluoromethyl)phenyl)-2-(methylthio)nicotinamide
1
3a-19: white powder; yield, 74.8%; mp, 153−154 °C; H NMR (400
MHz, DMSO-d6) δ 2.50 (s, 3H, S−CH3), 7.32 (dd, 1H, J = 6.5, 4.8 Hz,
Py−H), 7.87 (s, 1H, Ph−H), 8.05 (dd, 1H, J = 7.6, 1.7 Hz, Py−H), 8.41
(s, 2H, Ph−H), 8.65 (dd, 1H, J = 4.8, 1.6 Hz, Py−H), 11.09 (s, 1H,
CONH); MS (ESI), 281.04 (C15H10F6N2OS, [M + H]+). Anal. Calcd
for C15H10F6N2OS: C, 47.37; H, 2.65; N, 7.37. Found: C, 47.35; H, 2.99;
N, 7.15.
N-(3-Fluorophenyl)-2-(methylthio)nicotinamide 3a-11: white
powder; yield, 83.2%; mp, 171−172 °C; 1H NMR (400 MHz,
DMSO-d6) δ 2.49 (s, 3H, S−CH3), 7.12 (dt, 1H, J = 9.0, 2.5 Hz, Ph−
H), 7.28 (dd, 1H, J = 7.6, 4.9 Hz, Py−H), 7.38−7.42 (m, 1H, Ph−H),
7.46−7.48 (m, 1H, Py−H), 7.69 (td, 1H, J = 11.6, 2.0 Hz, Ph−H), 7.94
(dd, 1H, J = 7.6, 1.7 Hz, Ph−H), 8.60 (dd, 1H, J = 4.9, 1.7 Hz, Py−H),
10.68 (s, 1H, CONH); MS (ESI), 263.06 (C13H11FN2OS, [M + H]+).
2-(Methylthio)-N-(3,4,5-trifluorophenyl)nicotinamide 3a-20:
1
white powder; yield, 60.3%; mp, 146−147 °C; H NMR (400 MHz,
DMSO-d6) δ 2.49 (s, 3H, S−CH3), 7.30 (dd, 1H, J = 7.6, 4.9 Hz, Py−H),
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dx.doi.org/10.1021/jf405437k | J. Agric. Food Chem. 2014, 62, 4063−4071