Page 5 of 9
The Journal of Organic Chemistry
temperature, which was evaporated in vacuum to obtain crude
products. Finally, the crude products were purified by silica
gel column chromatography to obtain target products 3a-z.
3-(4-Fluorobenzoyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole
1
2
3
4
5
6
7
8
(3g). Eluent = petroleum ether/ethyl acetate (20:1). Yield 63
o
1
mg (73%), white solid, mp 124.3-125.8 C. H NMR (400
MHz, CDCl3, ppm) δ 8.43-8.40 (m, 2H), 8.30-8.27 (m, 2H),
7.29-7.22 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ
181.2, 175.7, 168.0 (d, J = 66.7 Hz), 166.0, 165.0 (d, J = 64.8
Hz), 133.6 (d, J = 9.7 Hz), 131.4, 131.0 (d, J = 9.4 Hz), 119.6
(d, J = 3.1 Hz), 116.7 (d, J = 22.4 Hz), 116.0 (d, J = 22.0 Hz).
ESI-HRMS [M+H]+ m/z calcd for C15H8F2N2O2 286.0554,
found 286.0537.
3-Benzoyl-5-phenyl-1,2,4-oxadiazole (3a).3b,19 Eluent
petroleum ether/ethyl acetate (20:1). Yield 48 mg (64%),
=
o
o
1
white solid, mp 91.3-92.7 C (lit.19 mp 92 C). H NMR (300
MHz, CDCl3, ppm) δ 8.24 (d, J = 7.6 Hz, 2H), 8.18-8.15 (m,
2H), 7.62-7.53 (m, 2H), 7.47-7.43 (m, 4H). 13C{1H} NMR
(100 MHz, CDCl3, ppm) δ 183.0, 176.5, 166.2, 135.1, 134.6,
133.4, 130.7, 129.2, 128.7, 128.5, 123.4. ESI-MS [M+H]+ m/z
251.1. The structure of 3a was further confirmed by X-ray
crystallagraply (Scheme S1).
9
3-(4-Fluorobenzoyl)-5-(2-thienyl)-1,2,4-oxadiazole
(3h).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Eluent = petroleum ether/ethyl acetate (10:1). Yield 62 mg
o
1
(75%), white solid, mp 146.3-47.5 C. H NMR (300 MHz,
CDCl3, ppm) δ 8.20 (d, J = 8.6 Hz, 2H), 7.95 (d, J = 2.8 Hz,
1H), 7.64 (d, J = 4.9 Hz, 1H), 7.43 (d, J = 8.6 Hz, 2H), 7.17-
7.14 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3, ppm) δ 181.5,
172.3, 165.8, 141.4, 133.4, 113.3, 133.1, 132.0, 129.1, 128.8,
124.6. ESI-HRMS [M+H]+ m/z calcd for C13H7FN2O2S
274.0212, found 274.0220.
3-Benzoyl-5-(4-fluorophenyl)-1,2,4-oxadiazole (3b). Eluent
= petroleum ether/ethyl acetate (20:1). Yield 55 mg (68%),
o
1
white solid, mp 119.4-120.3 C. H NMR (400 MHz, CDCl3,
ppm) δ 8.29-8.22 (m, 4H), 7.67-7.63 (m, 1H), 7.53-7.49 (m,
2H), 7.24-7.19 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3,
ppm) δ 182.9, 175.6, 167.1, 165.4 (d, J = 265.1 Hz), 135.0,
134.6, 131.0 (d, J = 9.4 Hz), 130.6, 128.7, 119.7 (d, J = 3.3
Hz), 116.7 (d, J = 22.4 Hz). ESI-HRMS [M+H]+ m/z calcd for
C15H9FN2O2 268.0648, found 268.0623.
3-(3-Fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole (3i). Eluent
= petroleum ether/ethyl acetate (20:1). Yield 59 mg (73%),
o
1
white solid, mp 104.1-105.5 C. H NMR (300 MHz, CDCl3,
ppm) δ 8.18 (d, J = 7.3 Hz, 2H), 8.09 (d, J = 7.8 Hz, 1H), 7.97
(d, J = 9.4 Hz, 1H), 7.60-7.55 (m, 1H), 7.52-7.43 (m, 3H),
7.34-7.28 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3, ppm) δ
181.6 (d, J = 2.6 Hz), 165.9, 164.3, 161.0, 136.8 (d, J = 6.9
Hz), 133.6, 130.4 (d, J = 7.7 Hz), 129.3, 128.5, 126.6 (d, J =
3.0 Hz), 123.1, 121.7 (d, J = 22.4 Hz), 117.3 (d, J = 21.3 Hz).
ESI-HRMS [M+H]+ m/z calcd for C15H9FN2O2 268.0648,
found 268.0637.
3-Benzoyl-5-(2-chlorophenyl)-1,2,4-oxadiazole (3c). Eluent
= petroleum ether/ethyl acetate (20:1). Yield 57 mg (67%),
o
1
white solid, mp 83.2-84.9 C. H NMR (300 MHz, CDCl3,
ppm) δ 8.27 (d, J = 7.7 Hz, 2H), 8.14 (d, J = 7.7 Hz, 1H),
7.65-7.60 (m, 1H), 7.55-7.46 (m, 4H), 7.41-7.36 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 182.7, 175.2, 165.8,
135.1, 134.7, 134.1, 133.8, 132.4, 131.5, 130.7, 128.7, 127.2,
122.8. ESI-HRMS [M+H]+ m/z calcd for C15H9ClN2O2
284.0453, found 284.0431.
3-(3-Fluorobenzoyl)-5-(4-chlorophenyl)-1,2,4-oxadiazole
(3j). Eluent = petroleum ether/ethyl acetate (20:1). Yield 64
1
mg (70%), white solid, mp 96.8-97.1 oC. H NMR (400 MHz,
3-Benzoyl-5-(2-methylphenyl)-1,2,4-oxadiazole (3d). Eluent
CDCl3, ppm) δ 8.28-8.24 (m, 2H), 8.14-8.12 (m, 1H), 8.03-
8.01 (m, 1H), 7.54-7.49 (m, 1H), 7.37-7.35 (m, 1H), 7.26-7.21
(m, 1H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 181.4 (d, J
= 2.6 Hz), 175.5, 165.9, 163.9, 161.4, 136.6 (d, J = 6.9 Hz),
135.6, 133.6, 130.6, 130.6 (d, J = 7.7 Hz), 128.5, 126.6, 126.6,
126.6, 124.7, 121.8 (d, J = 21.4 Hz), 117.3 (d, J = 23.4 Hz).
ESI-HRMS [M+H]+ m/z calcd for C15H8FClN2O2 302.0258,
found 302.0252.
= petroleum ether/ethyl acetate (20:1). Yield 51 mg (64%),
1
yellow liquid. H NMR (300 MHz, CDCl3, ppm) δ 8.36-8.32
(m, 2H), 8.23-8.20 (m, 1H), 7.69-7.67 (m, 1H), 7.58-7.48 (m,
3H), 7.40-7.37 (m, 2H), 2.78 (s, 3H). 13C{1H} NMR (75 MHz,
CDCl3, ppm) δ 183.2, 177.2, 165.9, 139.5, 135.2, 134.6, 132.9,
132.1, 130.6, 130.7, 128.7, 126.4, 122.5, 22.1. ESI-HRMS
[M+H]+ m/z calcd for C16H12N2O2 264.0899, found 264.0911.
3-Benzoyl-5-(4-methylphenyl)-1,2,4-oxadiazole (3e). Eluent
3-(3-Fluorobenzoyl)-5-(4-methylphenyl)-1,2,4-oxadiazole
= petroleum ether/ethyl acetate (20:1). Yield 49 mg (62%),
(3k). Eluent = petroleum ether/ethyl acetate (20:1). Yield 54
o
1
white solid, mp 91.2-92.1 C. H NMR (300 MHz, CDCl3,
ppm) δ 8.26 (d, J = 7.5 Hz, 2H), 8.07 (d, J = 8.2 Hz, 2H),
7.64-7.59 (m, 1H), 7.51-7.46 (m, 2H), 7.30 (d, J = 8.1 Hz, 2H),
2.39 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 183.2,
176.7, 166.1, 144.4, 135.2, 134.5, 130.7, 129.9, 128.7, 128.5,
120.6, 21.8. ESI-HRMS [M+H]+ m/z calcd for C16H12N2O2
264.0899, found 264.0917.
o
1
mg (64%), white solid, mp 114.6-115.5 C. H NMR (300
MHz, CDCl3, ppm) δ 8.19-8.13 (m, 3H), 8.05 (d, J = 9.5 Hz,
1H), 7.58-7.51 (m, 1H), 7.42-7.36 (m, 3H), 2.46 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3, ppm) δ 181.8, 176.8, 165.9,
163.9, 161.4, 144.5, 137.0 (d, J = 6.8 Hz), 130.4 (d, J = 7.6
Hz), 130.0, 128.5, 126.6 (d, J = 3.0 Hz), 121.6 (d, J = 21.5 Hz),
120.5, 117.2 (d, J = 23.6 Hz), 21.8. ESI-HRMS [M+H]+ m/z
calcd for C16H11FN2O2 282.0805, found 282.0807.
3-(4-Fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole (3f).3a Elu-
ent = petroleum ether/ethyl acetate (20:1). Yield 64 mg (80%),
3-(3-Fluorobenzoyl)-5-(4-methoxyphenyl)-1,2,4-oxadiazole
o
o
1
white solid, mp 105.4-106.7 C (lit.3a mp 106-108 C). H
NMR (300 MHz, CDCl3, ppm) δ 8.35-8.31 (m, 2H), 8.17 (d, J
= 7.4 Hz, 2H), 7.59-7.55 (m, 1H), 7.51-7.46 (m, 2H), 7.19-
7.12 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3, ppm) δ 181.3,
176.6, 116.7 (d, J = 257.9 Hz), 166.0, 133.6, 133.5, 131.5 (d, J
= 2.9 Hz), 129.3, 128.5, 123.2, 116.0 (d, J = 22.0 Hz). ESI-MS
[M+H]+ m/z 268.8.
(3l). Eluent = petroleum ether/ethyl acetate (20:1). Yield 57
o
1
mg (64%), white solid, mp 126.6-127.1 C. H NMR (300
MHz, CDCl3, ppm) δ 8.23-8.16 (m, 3H), 8.08-8.04 (m, 1H),
7.58-7.51 (m, 1H), 7.43-7.36 (m, 1H), 7.05 (d, J = 8.9 Hz, 2H),
3.92 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3, ppm) δ 181.9,
176.6, 165.9, 163.9, 163.8, 161.4, 144.5, 137.0 (d, J = 7.0 Hz),
130.5, 130.4 (d, J = 7.6 Hz), 126.6 (d, J = 3.0 Hz), 121.6 (d, J
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