The Journal of Organic Chemistry
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silica gel (EtOAc/hexane 5:95À10:90): pale yellow solid; yield 95%; mp
85À88 °C (lit.7a mp 83À85 °C); Rf (10% EtOAc/hexane) 0.30; IR
(KBr, cmÀ1) 2843, 1658, 1581, 1460, 1399, 1372, 1261, 740; 1H NMR
(CDCl3, 400 MHz) δ 3.01 (t, J = 6.4 Hz, 2H), 3.96 (t, J = 6 Hz, 2H), 4.86
(s, 2H), 7.02 (t, J = 7.8 Hz, 1H), 7.37À7.15 (m, 6H), 7.38 (d, J = 7.6 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 28.5, 43.1, 47.2, 108.7, 116.3, 120.5,
123.9, 126.4, 126.5, 126.8, 128.8, 132.4, 134.0, 143.2, 148.8, 162.0;
HRESI-MS (m/z) calcd for C16H14N2O (M + H) 251.1184, found (M + H)
251.1183
2-(4-Benzhydrylpiperazin-1-yl)benzoxazole (3g). Prepared
as shown in the general experimental procedure and purified on silica gel
(EtOAc/hexane 10:90À15:85): pale yellow solid; yield 80%; mp
164À168 °C; Rf (20% EtOAc/hexane) 0.30; IR (KBr, cmÀ1) 2815,
1636, 1578, 1455, 1265, 1240, 1005, 742; 1H NMR (CDCl3, 400 MHz)
δ 2.51 (t, J = 5 Hz, 4H), 3.69 (t, J = 5 Hz, 4H), 4.28 (s, 1H), 7.00 (dt, J1 =
1 Hz, J2 = 7.8 Hz, 1H), 7.14 (dt, J1 = 1 Hz, J2 = 7.6 Hz, 1H), 7.35À7.18
(m, 8H), 7.44À7.42 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 45.8,
51.1, 76.0, 108.7, 116.2, 120.6, 123.9, 127.2, 127.9, 128.6, 142.1, 143.1,
148.7, 162.2. Anal. Calcd for C24H23N3O: C, 78.02; H, 6.27; N, 11.37.
Found: C, 78.24; H, 6.30; N, 11.21.
3.80À3.76 (m, 2H), 3.86À3.84 (m, 2H), 6.79 (d, J = 8.1 Hz), 7.14À7.09
(m, 2H); 13CNMR(CDCl3, 100 MHz) δ21.5, 27.1, 46.3, 46.9, 47.1, 57.3,
58.0, 107.9, 116.33 120.8, 133.5, 143.4, 146.9, 162.4; HRESI-MS (m/z)
calcd for C14H19N3O(M + Na) 268.1426, found (M + Na) 268.1425.
2-(4-Morpholinyl)-5-phenylbenzoxazole (3m)7e. Prepared
as shown in the general experimental procedure and purified on silica
gel (EtOAc/hexane 15:85À20:80): beige solid; yield 92%; mp
106À110 °C (lit.7e 105À110 °C); Rf (20% EtOAc/hexane) 0.30; IR
(KBr, cmÀ1) 2915, 2955,2969, 2856, 1638, 1579, 1465, 1446, 1425,
1385, 1357, 1303, 1274, 1258, 1207, 1191, 1069, 1058, 981, 894, 761,
699, 591, 515; 1H NMR (CDCl3, 400 MHz) δ 1.66 (s, 6H), 3.65 (s, 6H),
7.29À7.21 (m, 3H), 7.40 (t, J = 7.4 Hz, 2H), 7.58À7.55 (m, 3H); 13C
NMR (CDCl3, 100 MHz) δ 45.6, 66.0, 108.7, 115.0, 120.2, 126.8, 127.2,
128.6, 137.8, 141.4, 143.4, 148.2, 162.4; HRESI-MS (m/z) calcd for
C17H16N2O2 (M + H) 281.1290, found (M + H) 281.1299.
5-Phenyl-2-(piperidin-1-yl)benzoxazole (3n)7a. Prepared as
shown in the general experimental procedure and purified on silica gel
(EtOAc/hexane 15:85À20:80): pink solid; yield 91%; mp 117À121 °C
(lit.7a mp 118À120 °C); Rf (20% EtOAc/hexane) 0.30; IR (KBr, cmÀ1
)
2938, 2922, 2854, 1647, 1638, 1578, 1466, 762; 1H NMR (CDCl3, 400
MHz) δ 3.67 (q, J = 2 Hz, 4H), 3.76 (q, J = 4.4 Hz, 4H), 7.32À7.23 (m,
3H), 7.41 (t, J = 7.4 Hz, 2H), 7.59À7.56 (m, 3H); 13C NMR (CDCl3,
100 MHz) δ 23.9, 25.1, 46.5, 108.4, 114.5, 119.6, 126.7, 127.1, 128.5,
128.7, 137.5, 141.5, 143.7, 148.2, 162.6; HRESI-MS (m/z) calcd for
C18H18N2O (M + H) 279.1497, found (M + H) 279.1497.
N,N-Dibenylbenzoxazol-2-amine (3h)1. Prepared as shown in
the general experimental procedure and purified on silica gel (EtOAc/
hexane 5:95À10:90): colorless liquid; yield 95%; Rf (10% EtOAc/
hexane) 0.30; IR (KBr, cmÀ1) 3027, 1640, 1577, 1456, 1401, 1241, 821,
739, 698; 1H NMR (CDCl3, 400 MHz) δ 4.69 (s, 4H), 7.03 (t, J = 8.9
Hz, 1H), 7.22À7.16 (m, 1H), 7.35À7.25 (m, 11H), 7.40 (d, J = 7.8 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 50.3, 108.8, 116.2, 120.5, 124.0,
127.7, 127.9, 128.7, 136.2, 143.4, 148.8, 163.0; HRESI-MS (m/z) calcd
for C21H18N2O (M + Na) 337.1317, found (M + Na) 337.1317.
5-Methyl-2-(piperidin-1-yl)benzoxazole (3i)7e. Prepared as
shown in general experimental procedure and purified on silica gel
(EtOAc/hexane 5:95À10:90): white solid; yield 92%; mp 98À100 °C
2-(N-Benzyl-N-methylamino)-5-phenylbenzoxazole (3o)7e.
Prepared as shown in the general experimental procedure and purified on
silica gel (EtOAc/hexane 10:90À15:85): beige solid; mp yield 93%; mp
97À100 °C (lit.7e mp 96À100 °C); Rf (20% EtOAc/hexane) 0.30; IR
(KBr, cmÀ1) 3028, 1641, 1580, 1416, 1394, 1253, 1202, 1115, 812, 758,
697; 1H NMR (CDCl3, 400 MHz) δ 3.14 (s, 2H), 4.77 (s, 2H),
7.25À7.23 (m, 1H), 7.36À7.29 (m, 7H), 7.44À7.40 (m, 2H),
7.60À7.58 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ 35.2, 53.8, 108.6,
114.8, 119.8, 126.8, 127.3, 127.6, 127.7, 128.7, 128.7, 136.3, 137.7, 141.6,
144.0, 148.6, 163.4; HRESI-MS (m/z) calcd for C21H18N2O (M + H)
315.1497, found (M + H) 315.1499.
2-Morpholino-6-nitrobenzoxazole (3p). Prepared as shown in
the general experimental procedure and purified on silica gel (EtOAc/
hexane 10:90À15:85): yellow solid; yield 84%; mp 140À144 °C; Rf
(30% EtOAc/hexane) 0.30; IR (KBr, cmÀ1) 2982, 2918, 1651, 1589,
1504, 1322, 1294, 1103, 851; 1H NMR (CDCl3, 400 MHz) δ 3.77 (t, J =
5.3 Hz, 4H), 3.85 (t, J = 4.3 Hz, 4H), 7.34 (d, J = 8.6 Hz, 1H), 8.20À8.14
(m, 2H); 13C NMR (CDCl3, 100 MHz) δ 45.7, 66.0, 105.2, 115.1, 121.5,
141.6, 147.8, 149.7, 164.5; HRESI-MS (m/z) calcd for C11H11N3O4 (M+Na)
272.0647, found (M + H) 272.0643.
6-Nitro-2-(piperidin-1-yl)benzoxazole (3q). Prepared as shown
in the general experimental procedure and purified on silica gel (EtOAc/
hexane 10:90À15:85): yellow solid; yield 85%; mp 102À106 °C; Rf (30%
EtOAc/hexane) 0.30; IR (KBr, cmÀ1) 2947, 2863, 1651, 1587, 1506, 1449,
1369, 1332,1320, 1291, 1024, 803; 1H NMR (CDCl3, 400 MHz) δ 1.72 (s,
6H), 3.73 (s, 4H), 7.28 (d, J = 8.7 Hz, 1H), 8.17À8.09 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 23.8, 25.6, 46.7, 104.7, 114.5, 121.5, 141.1, 147.8,
150.4, 164.8; HRESI-MS (m/z) calcd for C12H13N3O3(M + Na)
270.0855, found (M + Na) 270.0854.
N-Benzyl-N-methyl-6-nitrobenzoxazol-2-amine (3r). Prepared
as shown in the general experimental procedure and purified on silica gel
(EtOAc/hexane 10:90À15:85): yellow solid; yield 80%; mp 100À104 °C;
Rf (20% EtOAc/hexane) 0.30; IR (neat, cmÀ1) 1653, 1591, 1510, 1466,
1330, 1283, 1132, 819; 1H NMR (CDCl3, 400 MHz) δ 3.19 (s, 3H), 4.80
(s, 2H), 7.39À7.31 (m, 6H), 8.19À8.13 (m, 2H); 13C NMR (CDCl3, 100
MHz) δ 35.2, 54.0, 105.0, 114.7, 121.4, 127.7, 128.1, 128.9, 135.3, 141.2,
147.9, 150.3, 165.6; HRESI-MS (m/z) calcd for C15H13N3O3(M + Na)
306.0855, found (M + Na) 306.0854.
(lit.7e mp 94À97 °C); Rf (20% EtOAc/hexane) 0.20; IR (KBr, cmÀ1
)
1
2940, 2855, 1656, 1587, 1440, 1292, 1259, 1183, 1019, 889, 792; H
NMR (CDCl3, 400 MHz) δ 1.65 (s, 6H), 2.37 (s, 3H), 3.63 (s, 4H), 6.78
(d, J = 8 Hz, 1H), 7.08 (d, J = 8 Hz, 1H), 7.13 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 21.4, 23.9, 25.1, 107.8, 116.3, 120.8, 133.3, 143.2,
146.7, 162.4; HRESI-MS (m/z) calcd for C13H16N2O (M + H)
217.1341, found (M + H) 217.1346 .
5-Methyl-2-(4-methyl-1-piperazinyl)benzoxazole (3j)11a
.
Prepared as shown in the general experimental procedure and purified
on silica gel (EtOAc/hexane 10:90À20:80): white solid; yield 82%; mp
65À67 °C (lit.11a mp 63À64 °C); Rf (20% EtOAc/hexane) 0.20; IR
(KBr, cmÀ1) 2919, 2850, 2803, 1645, 1574, 1449, 1281, 1268, 1171,
1147, 1003, 803; 1H NMR (CDCl3, 400 MHz) δ 2.34 (s, 3H), 2.38 (s,
3H), 2.51 (t, J = 5.1 Hz, 4H), 3.71 (t, J = 5 Hz, 4H), 6.80À6.82 (m, 1H),
7.15À7.10 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 21.5, 45.5, 46.2,
54.2, 108.0, 116.7, 121.3, 133.6, 143.2, 146.9, 162.6; HRESI-MS (m/z)
calcd for C13H17N3O (M + H) 232.1450, found (M + H) 232.1454.
5-Methyl-2-thiomorpholinobenzoxazole (3k). Prepared as
shown in the general experimental procedure and purified on silica gel
(EtOAc/hexane 5:95À7:93): colorless liquid; yield 60%; Rf (10%
EtOAc/hexane) 0.40; IR (KBr, cmÀ1) 2916, 1633, 1583, 1260, 1180,
956; 1H NMR (CDCl3, 400 MHz) δ 2.39 (s, 3H), 2.72 (t, J = 5 Hz, 4H),
3.98 (t, J = 5 Hz, 4H), 6.82 (d, J = 8 Hz, 1H), 7.15À7.10(m, 2H); 13C
NMR (CDCl3, 100 MHz) δ 21.5, 26.0, 48.0, 108.0, 116.7, 121.4, 133.7,
142.9, 146.8, 161.8; HRESI-MS (m/z) calcd for C12H14N2OS (M + H)
235.0905, found (M + H) 235.0907.
5-Methyl-2-(4-methyl-1,4-diazepan-1-yl)benzoxazole (3l).
Prepared as shown in the general experimental procedure and purified
on silica gel (EtOAc/hexane 25:75À40:60): gray solid; yield 80%; mp
66À70 °C; Rf (50% EtOAc/hexane) 0.20; IR (KBr, cmÀ1) 2945, 2788,
1638, 1584, 1181, 791; 1H NMR (CDCl3, 400 MHz) δ 2.03À2.09 (m,
2H), 2.38 (s, 3H), 2.41 (s, 3H), 2.67À2.64 (m, 2H), 2.79À2.76 (m, 2H),
7942
dx.doi.org/10.1021/jo201402a |J. Org. Chem. 2011, 76, 7938–7944