The Journal of Organic Chemistry
Note
Representative Procedure for the Synthesis of Benzox-
azoles. An oven-dried reaction tube (25 mL) with a magnetic stir bar
was charged with Ts(OH)·H2O (9.51 mg, 0.1 mmol), CuI (9.50 mg,
0.1 mmol), 2-aminophenol (1a, 54.53 mg, 0.5 mmol), 2,4-pentane-
dione (2a, 75.0 mg, 0.75 mmol), and CH3CN (4 mL). The reaction
mixture was sealed and stirred at 80 °C for 16 h. The solvent was
removed under reduced pressure, and the residue obtained was
purified via silica gel chromatography (eluent: ethyl acetate/petroleum
ether = 1:5) to afford 2-methylbenzo[d]oxazole (3a) as a colorless oil
(54.7 mg, 82% yield).
5-Chloro-2-ethylbenzo[d]oxazole (3l):10 Yield 69%, 62.6 mg,
white solid; H NMR (400 MHz, CDCl3) δ 1.44 (t, J = 7.5 Hz, 3H),
1
2.95 (q, J = 7.5 Hz, 2H), 7.25 (d, J = 8.5 Hz, 1H), 7.38 (d, J = 8.5 Hz,
1H), 7.64 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 10.9, 22.3, 111.1,
119.7, 124.8, 129.6, 142.6, 149.5, 169.7.
6-Chloro-2-methylbenzo[d]oxazole (3m):11 Yield 89%, 74.4
mg, off white solid; 1H NMR (400 MHz, CDCl3) δ 2.63 (s, 3H), 7.27
(d, J = 8.4 Hz, 1H), 7.47 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 14.7, 111.0, 120.0, 124.9, 130.2, 140.4, 151.3,
164.7.
2-Methylbenzo[d]oxazole (3a):5b Yield 82%, 54.7 mg, colorless
oil; 1H NMR (400 MHz, CDCl3) δ 2.63 (s, 3H), 7.27−7.29 (m, 2H),
7.45−7.47 (m, 1H), 7.64−7.67 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.7, 110.4, 119.6, 124.3, 124.6, 141.7, 151.2, 164.0.
2-Ethylbenzo[d]oxazole (3b):5b Yield 76%, 56.0 mg, colorless
oil; 1H NMR (400 MHz, CDCl3) δ 1.47 (t, J = 7.6 Hz, 3H), 2.97 (q, J
= 7.6 Hz, 2H), 7.29−7.31 (m, 2H), 7.47−7.50 (m, 1H), 7.68−7.70 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 10.9, 22.2, 110.2, 119.5, 124.0,
124.4, 141.4, 150.8, 168.1.
6-Chloro-2-ethylbenzo[d]oxazole (3n): Yield 66%, 59.5 mg, off
white solid, mp 40−42 °C; 1H NMR (400 MHz, CDCl3) δ 1.45 (t, J =
7.5 Hz, 3H), 2.94 (q, J = 7.5 Hz, 2H), 7.28 (dd, J = 7.8, 1.4 Hz, 1H),
7.50 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
10.9, 22.3, 111.1, 120.2, 124.8, 130.2, 140.4, 151.4, 169.8; IR (KBr)
3104, 2983, 1618, 1576, 1451, 1226, 1153, 924, 859, 828, 733 cm−1;
HRMS (EI) calcd for C9H8NOCl 181.0294 [M]+; found 181.0288.
5-Bromo-2-methylbenzo[d]oxazole (3o):9 Yield 80%, 84.0 mg,
1
white solid; H NMR (400 MHz, CDCl3) δ 2.63 (s, 3H), 7.33(d, J =
2-Isopropylbenzo[d]oxazole (3c):5b Yield 25%, 20.0 mg,
8.6 Hz, 1H), 7.39 (d, J = 8.6 Hz, 1H), 7.77 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 14.7, 111.5, 116.9, 122.5, 127.5, 143.2, 150.0, 165.2.
5-Bromo-2-ethylbenzo[d]oxazole (3p): Yield 73%, 82.2 mg, off
white solid, mp 52−54 °C; 1H NMR (400 MHz, CDCl3) δ 1.44 (t, J =
7.6 Hz, 3H), 2.95 (q, J = 7.6 Hz, 2H), 7.33 (d, J = 8.6 Hz, 1H), 7.39
(d, J = 8.5 Hz, 1H), 7.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
10.9, 22.2, 111.5, 116.8, 122.6, 127.5, 143.1, 149.9, 169.4; IR (KBr)
3097, 2984, 1731, 1610, 1567, 1463, 1365, 1223, 1152, 929, 810 cm−1;
HRMS (EI) calcd for C9H8NOBr 224.9789, 226.9769; found
224.9795, 226.9770.
1
colorless oil; H NMR (400 MHz, CDCl3) δ 1.47 (d, J = 7.0 Hz,
6H) 3.22−3.29 (m, 1H), 7.29−7.31 (m, 2H), 7.47−7.50 (m, 1H),
7.68−7.70 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 20.6, 29.2, 110.2,
119.9, 124.3, 124.7, 141.5, 151.0, 171.6.
2-Phenylbenzo[d]oxazole (3d):9 Yield 49%, 48.0 mg, white
1
solid; H NMR (400 MHz, CDCl3) δ 7.34−7.38 (m, 2H), 7.52−7.60
(m, 4H), 7.77−7.79 (m, 1H), 8.25−8.27 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 110.8, 120.1, 124.7, 125.3, 127.3, 127.7, 129.1, 131.7,
142.2, 150.9, 163.2.
2,6-Dimethylbenzo[d]oxazole (3e):9 Yield 74%, 54.7 mg,
2-Methyl-5-nitrobenzo[d]oxazole (3q):10 Yield 65%, 58.0 mg,
white solid; 1H NMR (400 MHz, CDCl3) δ 2.71 (s, 3H), 7.58 (d, J =
8.9 Hz, 1H), 8.27 (dd, J = 8.9, 2.2 Hz, 1H), 8.54 (d, J = 2.2 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 14.8, 110.6, 116.0, 120.9, 142.1, 145.3,
154.7, 167.3.
1
colorless oil; H NMR (400 MHz, CDCl3) δ 2.47 (s, 3H), 2.62 (s,
3H), 7.11 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 14.4, 21.6, 110.3, 118.6, 125.1, 134.6,
139.2, 151.2, 163.2.
2-Ethyl-5-nitrobenzo[d]oxazole (3r):10 Yield 64%, 61.1 mg,
2-Ethyl-6-methylbenzo[d]oxazole (3f): Yield 70%, 56.4 mg,
colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.43 (t, J = 7.6 Hz, 3H),
2.45 (s, 3H), 2.92 (q, J = 7.6 Hz, 2H), 7.09 (d, J = 8.0 Hz, 1H), 7.26
(s, 1H) 7.52 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 11.2,
21.9, 22.4, 110.7, 119.1, 125.4, 134.9, 139.4, 151.3, 167.8; IR (neat)
3384, 2959, 2924, 1730, 1575, 1454, 1259, 1117, 1072, 1037, 923, 811
cm−1; HRMS (ES) calcd for C10H11NONa 184.0738 [M + Na]+;
found 184.0734.
1
white solid; H NMR (400 MHz, CDCl3) δ 1.49 (t, J = 7.6 Hz, 3H),
3.03 (q, J = 7.6 Hz, 2H), 7.58 (d, J = 8.9 Hz, 1H), 8.27 (dd, J = 8.9, 2.2
Hz, 1H), 8.55 (d, J = 2.1 Hz, 1H).
5-Nitro-2-phenylbenzo[d]oxazole (3s):5c Yield 40%, 48.3 mg,
1
white solid; H NMR (400 MHz, CDCl3) δ 7.53−7.62 (m, 3H), 7.66
(d, J = 8.9 Hz, 1H), 8.25 (d, J = 7.8 Hz, 2H), 8.30 (d, J = 8.9 Hz, 1H),
8.62 (s, 1H).
2,5-Dimethylbenzo[d]oxazole (3g):9 Yield 78%, 57.5 mg, light
2-(4-Methoxyphenyl)benzo[d]oxazole (3t):5b Yield 15%, 17
1
1
yellow solid; H NMR (400 MHz, CDCl3) δ 2.46 (s, 3H), 2.62 (s,
mg, white solid; H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), 7.03
3H), 7.09 (d, J = 8.3 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H), 7.45 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 9.2, 16.1, 104.2, 114.0, 120.1, 128.5,
136.4, 143.9, 158.6.
(dd, J = 8.9, 2.7 Hz, 2H), 7.31−7.34 (m, 2H), 7.53−7.57 (m, 1H),
7.73−7.75 (m, 1H), 8.20 (dd, J = 8.9, 2.7 Hz, 2H).
2-Methyloxazolo[4,5-b]pyridine (3u):12 Yield 59%, 39.4 mg,
white solid; 1H NMR (400 MHz, CDCl3) δ 2.71 (s, 3H), 7.28 (s, 1H),
7.78 (d, J = 8.0 Hz, 1H), 8.54 (s, 1H).
2-Ethyl-5-methylbenzo[d]oxazole (3h):10 Yield 72%, 58.1 mg,
colorless oil; 1H NMR (400 MHz, CDCl3) δ 1.43 (t, J = 7.6 Hz, 3H),
2.44 (s, 3H), 2.93 (q, J = 7.6 Hz, 2H), 7.08 (d, J = 8.2 Hz, 1H), 7.33
(d, J = 8.3 Hz, 1H), 7.44 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
10.9, 21.5, 22.2, 109.6, 119.5, 125.4, 133.8, 141.6, 149.1, 168.2.
5-Methoxy-2-methylbenzo[d]oxazole (3i):9 Yield 75%, 61.3
mg, white solid; 1H NMR (400 MHz, CDCl3) δ 2.59 (s, 3H), 3.82 (s,
3H), 6.86 (dd, J = 8.8, 2.3 Hz, 1H), 7.13 (d, J = 2.3 Hz, 1H), 7.32 (dd,
J = 8.8, 1.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.5, 55.9, 102.7,
110.2, 112.6, 142.4, 145.6, 157.0, 164.6.
N-(2-Hydroxyphenyl)acetamide (4a):6a Yield 10%, 7.6 mg, off
white solid; 1H NMR (400 MHz, DMSO-d6) δ 2.10 (s, 3H), 6.76 (dd,
J = 7.5, 7.4 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.94 (dd, J = 7.6, 7.4 Hz,
1H), 7.69 (d, J = 7.8 Hz, 1H), 9.32 (s, 1H), 9.76 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 23.7, 115.9, 119.0, 122.4, 124.7, 126.5, 147.9,
169.0.
(E)-3-(2-Hydroxyphenylamino)-1,3-diphenylprop-2-en-1-
1
one (4b): Yellowish solid, mp 146−148 °C; H NMR (400 MHz,
DMSO-d6) δ 6.14 (s, 1H), 6.31 (d, J = 8.0 Hz, 1H), 6.46 (dd, J = 7.2,
7.2 Hz, 1H), 6.86 (dd, J = 7.6, 7.2 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H),
7.42−7.55 (m, 8H), 8.01 (d, J = 7.2 Hz, 2H), 10.09 (s, 1H), 12.66 (s,
1H); 13C NMR (100 MHz, DMSO-d6) δ 97.2, 116.5, 120.0, 125.3,
125.8, 128.0, 129.0, 129.1, 129.3, 130.4, 132.0, 137.1, 150.4, 162.3,
189.4. IR (KBr) 3376, 3154, 1587, 1479, 1343, 1285, 1222, 1096, 942,
851, 753, 695 cm-1; HRMS (ES) calcd for C21H18NO2 316.1338 [M +
H]+; found 316.1337; for C21H17NO2Na 338.1157 [M + Na]+; found
338.1153.
2-Ethyl-5-methoxybenzo[d]oxazole (3j): Yield 73%, 64.4 mg,
yellowish oil; 1H NMR (400 MHz, CDCl3) δ 1.43 (t, J = 7.6 Hz, 3H),
2.92 (q, J = 7.6 Hz, 2H), 3.83 (s, 3H), 6.87 (dd, J = 8.8, 2.4 Hz, 1H),
7.17 (d, J = 2.2 Hz, 1H), 7.33 (d, J = 8.8 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 10.9, 22.2, 55.9, 102.8, 110.3, 112.6, 142.2, 145.5,
157.0, 169.0; IR (neat) 2941, 1573, 1483, 1441, 1285, 1196, 1152,
1028, 839, 804 cm−1; HRMS (ES) calcd for C10H12NO2 178.0868 [M
+ H]+; found 178.0865.
5-Chloro-2-methylbenzo[d]oxazole (3k):9 Yield 67%, 56.3 mg,
off white solid; 1H NMR (400 MHz, CDCl3) δ 2.63 (s, 3H), 7.25 (d, J
= 8.6 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.62 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 14.7, 111.0, 119.5, 124.8, 129.6, 142.7, 149.6, 165.4.
N-(5-Chloro-2-hydroxyphenyl)acetamide (4c):6a Yield 29%,
1
26.9 mg, off white solid; H NMR (400 MHz, DMSO-d6) δ 2.11 (s,
3H), 6.86 (d, J = 8.6 Hz, 1H), 6.96 (dd, J = 2.2, 8.6 Hz, 1H), 7.96 (d, J
D
dx.doi.org/10.1021/jo500604x | J. Org. Chem. XXXX, XXX, XXX−XXX