The Journal of Organic Chemistry
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7.57 (d, J = 8.6 Hz, 1H), 7.36 (s, 1H), 7.25 (d, J = 7.0 Hz, 1H), 7.00 (d, J
= 8.2 Hz, 1H), 6.80 (d, J = 8.6 Hz, 1H), 3.86 (s, 3H), 2.42 (s, 3H), 2.40
(s, 3H), 2.2 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ (ppm) 164.4,
159.4, 150.1, 142.39, 142.36, 135.0, 133.9, 127.0, 124.7, 118.8, 117.0,
109.2, 108.5, 55.5, 21.6, 18.0, 12.7. HRMS (ESI-TOF) (m/z): [M +
Na]+ calcd for C17H17NNaO2S 322.0878, found 322.0883.
7.04−7.02 (m, 2H), 2.74 (s, 3H), 2.43 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ (ppm) 165.6, 150.2, 142.1, 134.0, 124.7, 118.3, 109.2,
21.4, 14.5. HRMS (ESI-TOF) (m/z): [M + H]+ calcd for
C9H10NOS180.0483, found 180.0482.
Reference Compound 5-Methylbenz[d]oxazol-2(3H)-one (3bb).27
White solid. Yield: 60% (8.94 g). Mp: 129−131 °C (lit.28 130−131 °C).
Rf (10% EtOAc/hexane): 0.4. IR (KBr, cm−1): 2926, 1791, 1737, 1459,
1498. 1H NMR (400 MHz, CDCl3): δ (ppm) 9.82 (br s, 1H), 7.08 (d, J
= 8.1 Hz, 1H), 6.94−6.90 (m, 2H), 2.37 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ (ppm) 156.6, 141.9, 134.2, 129.4, 123.1, 110.7, 109.6,
21.4. HRMS (ESI-TOF) (m/z): [M + Na]+ calcd for C8H7NNaO2
172.0372, found 172.0374.
2-((4-Methoxy-2,3-dimethylphenyl)thio)-6-methylbenz[d]oxazole
(3o). 3o was prepared as described in the typical experimental
procedure. The crude product was purified on a silica gel (100−200
mesh) column (EtOAc/hexane, 3:97). Faint yellow solid. Yield: 95%
(71 mg). Mp: 110−112 °C. Rf (5% EtOAc/hexane): 0.4. IR (KBr,
cm−1):1576, 1508, 1262, 1210, 1087. 1H NMR (400 MHz, CDCl3): δ
(ppm) 7.56 (d, J = 8.6 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.19 (s, 1H),
7.04 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.6 Hz, 1H), 3.85 (m, 3H), 2.43 (s,
3H), 2.42 (s, 3H), 2.2 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ
(ppm) 163.7, 159.3, 152.1, 142.3, 139.9, 134.9, 134.1, 127.0, 125.2,
118.2, 117.0, 110.2, 108.5, 55.5, 21.6, 18.0, 12.7. HRMS (ESI-TOF) (m/
z): [M + Na]+ calcd for C17H17NNaO2S 322.0878, found 322.0877.
2-((3,4-Dimethoxyphenyl)thio)naphth[2,3-d]oxazole (3p). 3p was
prepared as described in the typical experimental procedure. The crude
product was purified on a silica gel (100−200 mesh) column (EtOAc/
hexane, 10:90). Orange solid. Yield: 52% (84 mg). Mp: 93−95 °C. Rf
(20% EtOAc/hexane): 0.4. IR (KBr, cm−1): 1582, 1506, 1496, 1377,
1259, 1230, 1130, 1003, 1011. 1H NMR (400 MHz, CDCl3): δ (ppm)
8.43 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.70 (d, J = 8.9 Hz,
1H), 7.63−7.49 (m, 3H), 7.34 (dd, J1 = 8.3 Hz, J2 = 1.8 Hz, 1H), 7.26 (s,
1H), 6.93 (d, J = 8.4 Hz, 1H), 3.93−3.90 (m, 6H). 13C{1H} NMR (100
MHz, CDCl3): δ (ppm) 161.7, 150.6, 149.4, 149.3, 137.5, 131.0, 128.4,
127.9, 126.9, 125.7, 125.4, 125.2, 122.1,118.1, 117.4, 111.7, 110.4, 56.1,
56.0. HRMS (ESI-TOF) (m/z): [M + Na]+ calcd for C19H15NNaO3S
(M+ + Na): 360.0669, found 360.0670.
2-((3,4-Dimethoxyphenyl)thio)benzo[d]thiazole (3r). 3r was pre-
pared as described in the typical experimental procedure. The crude
product was purified on a silica gel (100−200 mesh) column (EtOAc/
hexane, 10:90 to 15:85). White solid. Yield: 28% (42 mg). Mp: 101−102
°C. Rf (20% EtOAc/hexane): 0.4. IR (KBr, cm−1): 1582, 1502, 1426,
1255, 1235, 1135. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.86 (d, J = 8.2
Hz, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.41−7.33 (m, 2H), 7.27−7.21 (m,
2H), 6.95 (d, J = 8.2 Hz, 1H), 3.95 (s, 3H), 3.89 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ (ppm) 171.6, 154.0, 151.2, 149.7, 135.3, 129.1,
126.0, 124.1, 121.7, 120.7, 120.2, 118.1, 111.8, 56.0, 55.9. HRMS (ESI-
TOF) (m/z): [M + Na]+ calcd for C15H13NNaO2S2 326.0285, found
326.0282.
4-((5-Methylbenz[d]oxazol-2-yl)thio)phenol (5a). 5a was prepared
as described in the typical experimental procedure. The crude product
was purified on a silica gel (100−200 mesh) column (EtOAc/hexane,
5:95 to 15:85). White solid. Yield: 68% (44 mg). Mp: 185−186 °C. Rf
(20% EtOAc/hexane): 0.4. IR (KBr, cm−1): 3233, 1588, 1491, 1460,
1
1230, 1153, 1091. H NMR (400 MHz, CDCl3): δ (ppm) 9.30 (br s,
1H), 7.42 (d, J = 8.2 Hz, 2H), 7.36−7.34 (m, 2H), 7.08 (d, J = 8.2 Hz,
1H), 6.68 (d, J = 8.2 Hz, 2H), 2.40 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 167.6, 159.6, 150.0, 140.8, 137.2, 134.7, 125.4, 117.83,
117.80, 114.0, 109.55, 21.3. HRMS (ESI-TOF) (m/z): [M + Na]+ calcd
for C14H12NNaO2S 258.0589, found 258.0590.
4-((5-Chlorobenz[d]oxazol-2-yl)thio)phenol (5b). 5b was prepared
as described in the typical experimental procedure. The crude product
was purified on a silica gel (100−200 mesh) column (EtOAc/hexane,
5:95 to 15:85). Brown crystalline solid. Yield: 84% (58 mg). Mp: 190−
192 °C. Rf (20% EtOAc/hexane): 0.4. IR (KBr, cm−1): 3437, 1618,
1460, 1286. 1H NMR (400 MHz, DMSO): δ (ppm) 10.16 (br s, 1H),
7.69 (s, 1H), 7.64 (d, J = 8.6 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.33−7.31
(m, 1H), 6.90 (d, J = 8.4 Hz, 2H). 13C{1H} NMR (100 MHz, DMSO): δ
(ppm) 165.9, 159.7, 150.1, 142.7, 137.1, 128.9, 124.3, 118.3, 116.9,
113.3, 115.5. HRMS (ESI-TOF) (m/z): [M + Na]+ calcd for
C13H8NNaO2SCl 299.9862, found 299.9863.
4-(Benz[d]oxazol-2-ylthio)-2,6-dimethylphenol (5c). 5c was pre-
pared as described in the typical experimental procedure. Pale yellow
solid. The crude product was purified on a silica gel (100−200 mesh)
column (EtOAc/hexane, 5:95 to 10:90). Yield: 89% (60 mg). Mp: 210−
212 °C. Rf (10% EtOAc/hexane): 0.4. IR (KBr, cm−1): 3413, 1649,
1507, 1452, 2452, 1320, 1257, 1204. 1H NMR (400 MHz, DMSO): δ
(ppm) 8.93 (s, 1H), 7.61−7.57 (m, 2H), 7.30−7.28 (m, 4H), 2.19 (s,
6H). 13C{1H} NMR (100 MHz, DMSO): δ (ppm) 163.9, 155.6, 151.2,
141.4, 135.2, 126.0, 124.6, 124.4, 118.5, 113.6, 110.3, 16.4. HRMS (ESI-
TOF) (m/z): [M + Na]+ calcd for C15H13NNaO2S 294.0565, found
294.0563.
4-((5-Chlorobenz[d]oxazol-2-yl)thio)-2,6-dimethylphenol (5d). 5d
was prepared as described in the typical experimental procedure. The
crude product was purified on a silica gel (100−200 mesh) column
(EtOAc/hexane, 10:90). Cream-colored solid. Yield: 79% (60 mg). Mp:
216−218 °C. Rf (10% EtOAc/hexane): 0.4. IR (KBr, cm−1): 3448, 1648,
1475, 1253, 1133. 1H NMR (400 MHz, DMSO): δ (ppm) 8.95 (br s,
1H), 7.69 (s, 1H), 7.63 (d, J = 8.6 Hz, 1H), 7.32−7.30 (m, 3H), 2.18 (s,
6H). 13C{1H} NMR (100 MHz, DMSO): δ (ppm) 166.1, 155.8, 150.0,
142.7, 135.3, 128.8, 126.0, 124.2, 118.2, 113.0, 111.5, 16.4. HRMS (ESI-
TOF) (m/z): [M + Na]+ calcd for C15H12ClNNaO2S 328.0175, found
328.0175.
2-((2,3,4-Trimethoxyphenyl)thio)benzo[d]thiazole (3s). 3s was
prepared as described in the typical experimental procedure. The
crude product was purified on a silica gel (100−200 mesh) column
(EtOAc/hexane, 10:90). White solid. Yield: 52% (43 mg). Mp: 108−
110 °C. Rf (10% EtOAc/hexane): 0.4. IR (KBr, cm−1): 1455, 1424,
1294, 1088, 1004. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.85 (d, J = 8.2
Hz, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.39 (dd, J1=
J2= 7.7 Hz, 1H), 7.25 (dd, J1 = J17= 0.9 Hz, 1H), 6.78 (d, J = 8.7 Hz, 1H),
3.94 (s, 3H), 3.92 (s, 3H), 3.91 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 171.3, 156.7, 155.2, 154.1, 143.2, 135.4, 132.3, 126.0,
124.0, 121.7, 120.7, 114.8, 107.9, 61.7, 61.0, 56.1. HRMS (ESI-TOF)
(m/z): [M + Na]+ calcd for C16H15NNaO3S 356.0391, found 356.0415.
5-Methyl-2-((4-(methylthio)phenyl)thio)benz[d]oxazole (3t). 3t
was prepared as described in the typical experimental procedure. The
crude product was purified on a silica gel (100−200 mesh) column
(EtOAc/hexane, 3:97 to 5:95). White solid. Yield: 79% (57 mg). Mp:
69−70 °C. Rf (5% EtOAc/hexane): 0.4. IR (KBr, cm−1): 1645, 1507,
1253,1147. 1H NMR (400 MHz, CDCl3): δ (ppm) 7.59 (d, J = 8.3 Hz,
2H), 7.38 (s, 1H), 7.29−7.26 (m, 3H), 7.04 (d, J = 8.2 Hz, 1H), 2.51 (s,
3H), 2.42 (s, 3H) 3.83 (3H, s). 13C{1H} NMR (100 MHz, CDCl3): δ
(ppm) 163.3, 150.1, 142.1, 141.7, 134.9, 134.2, 126.8, 125.2, 122.6,
119.0, 109.3, 21.4, 15.2. HRMS (ESI-TOF) (m/z): [M + Na]+ calcd for
C15H13NNaOS2 310.0336, found 310.0336.
3,5-Dimethyl-4-((5-methylbenz[d]oxazol-2-yl)thio)phenol (5e). 5e
was prepared as described in the typical experimental procedure. The
crude product was purified on a silica gel (100−200 mesh) column
(EtOAc/hexane, 10:90). White solid. Yield: 72% (52 mg). Mp: 248−
250 °C. Rf (20% EtOAc/hexane): 0.3. IR (KBr, cm−1): 3473, 3123,
2922, 1590, 1463, 1313, 1257, 1152, 1105, 1023. 1H NMR (400 MHz,
DMSO): δ (ppm) 10.07 (br, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.31 (s, 1H),
7.04 (d, J = 8.2 Hz, 1H), 6.67 (s, 2H), 2.32 (s, 3H), 2.29 (s, 6H).
13C{1H} NMR (100 MHz, DMSO): δ (ppm) 163.6, 159.5, 149.9, 145.3,
141.9, 134.5, 125.5, 118.6, 116.1, 114.3, 109.9, 21.9, 21.2. HRMS (ESI-
TOF) (m/z): [M + H]+ calcd for C16H16NO2S 286.0902, found
286.0902.
5-Methyl-2-(methylthio)benz[d]oxazole (3aa, Table 1, Entry 21).26
Yellow liquid. Yield: 42% (19 mg). White semisolid. Rf (10% EtOAc/
hexane): 0.4. IR (KBr, cm−1): 1499, 1477, 1255, 1153. 1H NMR (400
MHz, CDCl3): δ (ppm) 7.3855 (d, J = 0.6 Hz, 1H), 7.30−7.26 (m, 1H),
4-(Benz[d]oxazol-2-ylthio)-2,6-di-tert-butylphenol (5f). 5f was
prepared as described in the typical experimental procedure. The
K
dx.doi.org/10.1021/jo501793q | J. Org. Chem. XXXX, XXX, XXX−XXX