10.1002/cmdc.201800348
ChemMedChem
FULL PAPER
diluted with CH2Cl2 (70 mL). The organic layer was washed with saturated
aqueous sodium bicarbonate (70 mL), saturated aqueous sodium chloride
(70 mL), dried (NaSO4), and was concentrated to afford the mixture of
sulfoxide and sulfone. Flash chromatography (silica gel, 3:1
hexanes:EtOAc → 1:2 hexanes:EtOAc) afforded 59 as an off-colorless
crystalline solid (208 mg, 75%): m.p. 76.0–77.8 °C; 1H NMR (CDCl3, 400
MHz) δ 7.91 (m, 1H), 7.49 (m, 1H), 7.34 (m, 1H), 2.18 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 142.0, 141.0, 132.2, 128.5, 128.2, 127.8, 124.9, 42.6;
IR (film) νmax 3072, 2996, 2922, 2853, 2167, 2060, 1582, 1572, 1466, 1439,
1414, 1293, 1127, 1076, 1047, 936, 760, 714, 532, 515, 496, 467, 457,
443, 434, 428, 418, 404 cm-1; HRMS (EI+) m/z: [M + H]+ calcd for
C8H8NOS2, 198.0047; found, 198.0065.
1-Isothiocyanato-4-(methylsulfonyl)benzene (67):[45] The purification
of 61 also provided 67 as a colorless solid (91 mg, 30%): m.p. 133.7–
134.4 °C; 1H NMR (CDCl3, 400 MHz) δ 7.95 (m, 2H), 7.40 (m, 2H), 3.07 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 139.8, 138.9, 137.2, 129.4 (2C), 126.7
(2C), 44.6; IR (film) νmax 3092, 3067, 3008, 3021, 2926, 2192, 2079, 1653,
1587, 1576, 1559, 1540, 1506, 1301, 1284, 1172, 1142, 1085, 931, 832,
777, 727, 668, 531, 450, 441, 434, 430, 418, 414, 404 cm-1; HRMS (EI+)
m/z: [M + H]+ calcd for C8H8NO2S2, 213.9996; found, 213.9979.
1-(Isothiocyanatomethyl)-2-(methylsulfinyl)benzene (62): To
a
solution of 56 (174 mg, 0.89 mmol) in dry CH2Cl2 (2.80 mL) was slowly
added mCPBA (70%, 230 mg, 0.93 mmol). The reaction was stirred at rt
for 2.5 h and was diluted with CH2Cl2 (35 mL). The organic layer was
washed with saturated aqueous sodium bicarbonate (35 mL), saturated
aqueous sodium chloride (35 mL), dried (NaSO4), and was concentrated
to afford the mixture of sulfoxide and sulfone. Flash chromatography (silica
gel, 1:3 hexanes:EtOAc) afforded 62 as a yellow green oil (145 mg, 77%):
1H NMR (CDCl3, 400 MHz): δ 8.05 (dd, J = 7.8, 1.4 Hz, 1H), 7.64 (td, J =
7.3, 1.4 Hz, 1H), 7.58 (td, J = 7.3, 1.4 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H),
4.90 (s, 2H), 2.81 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 144.5, 132.4,
132.1, 131.6, 130.7, 129.4, 124.7, 45.6, 43.8; IR (film) νmax 3054, 2987,
2360, 2340, 1653, 1559, 1540, 1507, 1420, 1265, 896, 740, 705, 668 cm-
1; HRMS (EI+) m/z: [M + H]+ calcd for C9H10NOS2, 212.0204; found,
212.0217.
1-Isothiocyanato-2-(methylsulfonyl)benzene (65): The purification of
59 also provided 65 as a colorless solid (52 mg, 17%): m.p. 92.8–93.4 °C;
1H NMR (CDCl3, 400 MHz) δ 8.05 (dd, J = 7.8, 1.4, 1H), 7.64 (td, J = 7.8,
1.8, 1H), 7.45 (m, 2H), 3.22 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 141.3,
135.1, 134.5, 130.7, 129.9, 129.5, 127.5, 43.5; IR (film) νmax 3090, 3069,
3024, 3008, 2955, 2925, 2853, 2177, 2099, 1874, 1737, 1727, 1584, 1571,
1469, 1443, 1409, 1316, 1271, 1244, 1212, 1152, 1127, 1070, 1036, 955,
937, 875, 777, 759, 716, 654, 545, 536, 502, 475, 465, 454, 445, 431, 421,
413, 405 cm-1; HRMS (EI+) m/z: [M + H]+ calcd for C8H8NO2S2, 213.9996;
found, 213.9988.
1-Isothiocyanato-3-(methylsulfinyl)benzene (60): To a solution of 54
(254 mg, 1.40 mmol) in dry CH2Cl2 (4.20 mL) was slowly added mCPBA
(70%, 351 mg, 1.42 mmol). The reaction was stirred at rt for 2 h and was
diluted with CH2Cl2 (70 mL). The organic layer was washed with saturated
aqueous sodium bicarbonate (70 mL), saturated aqueous sodium chloride
(70 mL), dried (NaSO4), and was concentrated to afford the mixture of
sulfoxide and sulfone. Flash chromatography (silica gel, 3:1
hexanes:EtOAc → 1:2 hexanes:EtOAc) afforded 60 as a yellow oil (194
1-(Isothiocyanatomethyl)-3-(methylsulfinyl)benzene (63): To
a
solution of 57 (789 mg, 4.04 mmol) dissolved in dry CH2Cl2 (15.0 mL) was
slowly added mCPBA (70%, 1.64 g, 6.65 mmol). The reaction was stirred
at rt for 2 h and was diluted with CH2Cl2 (50 mL). The organic layer was
washed with saturated aqueous sodium bicarbonate (2 x 70 mL), saturated
aqueous sodium chloride (70 mL), dried (NaSO4), and was concentrated.
Flash chromatography (silica gel, 5:1:1 hexanes:CH2Cl2:EtOAc → 1:1
CH2Cl2:EtOAc) afforded 63 as a brown oil (156 mg, 18%): 1H NMR (CDCl3,
400 MHz) δ 7.16 (s, 1H), 7.60-7.52 (m, 2H), 7.46 (m, 1H), 4.80 (s, 2H),
2.74 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 147.0, 136.3, 134.0, 130.2,
129.6, 123.7, 122.0, 48.5, 44.2; IR (film) νmax 3455, 2997, 2923, 2853,
2178, 2095, 1599, 1476, 1429, 1342, 1084, 1049, 997, 957, 788, 710, 687
cm-1; HRMS (EI+) m/z: [M + H]+ calcd for C9H10NOS2, 212.0204; found,
212.0199.
1
mg, 70%): H NMR (CDCl3, 400 MHz) δ 7.57-7.48 (m, 3H), 7.33 (dt, J =
6.9, 2.3, 1H), 2.75 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 148.1, 138.3,
133.2, 130.7, 128.1, 122.1, 121.1, 44.2; IR (film) νmax 3055, 2996, 2923,
2196, 2104, 1586, 1574, 1545, 1536, 1532, 1474, 1421, 1415, 1299, 1279,
1248, 1085, 1079, 1050, 996, 960, 789, 680, 478, 470, 466, 448, 444, 436,
420, 415, 403 cm-1; HRMS (EI+) m/z: [M + H]+ calcd for C8H8NOS2,
198.0047; found, 198.0060.
1-Isothiocyanato-3-(methylsulfonyl)benzene (66):[45] The purification of
60 also provided 66 as a light yellow solid (37 mg, 13%): m.p. 75.2–
77.5 °C; 1H NMR (CDCl3, 400 MHz) δ 7.84 (dt, J = 7.8, 1.8 Hz, 1H), 7.82
(t, J = 1.8 Hz, 1H), 7.59 (t, J = 8.2 Hz, 1H), 7.49 (ddd, J = 8.2, 2.3, 0.9 Hz,
1H), 3.09 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 142.4, 139.4, 133.4, 131.0,
130.7, 125.8, 124.9, 44.6; IR (film) νmax 2955, 2923, 2853, 2092, 2072,
2022, 2012, 1985, 1963 ,1314, 1297, 1143, 1088, 1075, 970, 774, 731,
676, 575, 531, 517, 508, 493, 481, 458, 445, 440, 421, 412, 406 cm-1;
HRMS (EI+) m/z: [M + H]+ calcd for C8H8NO2S2, 213.9996; found,
213.9989.
1-(Isothiocyanatomethyl)-3-(methylsulfonyl)benzene
(69):
The
purification of 63 also provided 69 as a colorless solid (52 mg, 17%): m.p.
67.7–68.0 °C; 1H NMR (CDCl3, 400 MHz) δ 7.92 (dt, J = 6.4, 1.8 Hz, 1H),
7.88 (s, 1H), 7.66-7.59 (m, 2H), 4.83 (s, 2H), 3.07 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 141.6, 136.4, 134.7, 132.2, 130.4, 127.6, 126.0, 48.3, 44.7; IR
(film) νmax 3061, 3013, 2924, 2852, 2178, 2066, 1479, 1431, 1318, 1212,
1144, 1086, 962, 866, 759, 708 cm-1; HRMS (EI+) m/z: [M]+ calcd for
C9H9NO2S2, 227.0075; found, 227.0089.
1-(Isothiocyanatomethyl)-4-(methylsulfinyl)benzene (64): To
a
solution of 58 (125 mg, 0.64 mmol) in dry CH2Cl2 (1.70 mL) was slowly
added mCPBA (70%, 158 mg, 0.64 mmol). The reaction was stirred at rt
for 2 h and was diluted with CH2Cl2 (35 mL). The organic layer was washed
with saturated aqueous sodium bicarbonate (70 mL), saturated aqueous
sodium chloride (70 mL), dried (NaSO4), and was concentrated to afford
the mixture of sulfoxide and sulfone. Flash chromatography (silica gel, 1:1
hexanes:EtOAc → 1:1 CH2Cl2 ) afforded 64 as a light brown oil (35.9 mg,
24.9%): 1H NMR (CDCl3, 400 MHz) δ 7.69 (m, 2H), 7.50 (m, 2H), 4.81 (s,
2H), 2.74 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 140.7, 140.5, 134.4, 128.3,
127.8, 48.3, 44.6; IR (film) νmax 3420, 3055, 2927, 2854, 2361, 2337, 2188,
2096, 1636, 1456, 1436, 1410, 1317, 1265, 1091, 1091, 1018, 958, 896,
811, 739, 705, 668, 651 cm-1; HRMS (EI+) m/z: [M + H]+ calcd for
C9H10NOS2, 212.0204; found, 212.0206.
1-Isothiocyanato-4-(methylsulfinyl)benzene (61): To a solution of 55
(256 mg, 1.41 mmol) in dry CH2Cl2 (4.20 mL) was slowly added mCPBA
(70%, 358 mg, 1.45 mmol). The reaction was stirred at rt for 2 h and was
diluted with CH2Cl2 (70 mL). The organic layer was washed with saturated
aqueous sodium bicarbonate (70 mL), saturated aqueous sodium chloride
(70 mL), dried (NaSO4), and was concentrated to afford the mixture of
sulfoxide and sulfone. Flash chromatography (silica gel, 3:1
hexanes:EtOAc → 1:2 hexanes:EtOAc) afforded 61 as a light yellow solid
(171 mg, 62%): m.p. 74.7–77.5 °C; 1H NMR (CDCl3, 400 MHz) δ 7.65 (m,
2H), 7.37 (m, 2H), 2.73 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 144.5, 138.1,
134.4, 126.7 (2C), 125.1 (2C), 44.1; IR (film) νmax 3080, 3058, 3024, 2994,
2957, 2923, 2853, 2361, 2338, 2180, 2094, 1734, 1717, 1700, 1684, 1653,
1587, 1559, 1540, 1506, 1488, 1466, 1457, 1418, 1402, 1293, 1250, 1087,
1051, 1013, 955, 931, 831, 727, 676, 668, 516, 484, 472, 453, 440, 434,
417, 401 cm-1; HRMS (EI+) m/z: [M + H]+ calcd for C8H8NOS2, 198.0047;
found, 198.0032.
1-(Isothiocyanatomethyl)-4-(methylsulfonyl)benzene
(70):
The
purification of 64 also provided 70 as a green oil (92 mg, 68.6 %): 1H NMR
(CDCl3, 400 MHz) δ 8.00 (d, J = 8.2 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 4.86
(s, 2H), 3.08 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 140.8, 140.6, 134.6,
13
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