Y(OTf)3-catalyzed, one-pot synthesis of 1,2,4-oxadiazole derivatives

Article abstract of DOI:10.1080/00397910701577695

Direct one-step synthesis of 1,2,4-oxadiazole from ketones, nitriles, and nitric acid is described using yttrium triflate [Y(OTf)3] as the catalyst. The salient features of this method include a simple procedure, mild condition, easy purification, and goo

Full text of DOI:10.1080/00397910701577695

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Y(OTf)3‐Catalyzed, One‐Pot Synthesis of
1,2,4‐Oxadiazole Derivatives
Chuanming Yu a , Min Lei a , Weike Su a & Yuanyuan Xie a
a Zhejiang Key Laboratory of Pharmaceutical Engineering , College of
Pharmaceutical Sciences, Zhejiang University of Technology , Hangzhou,
China
Published online: 14 Dec 2007.
To cite this article: Chuanming Yu , Min Lei , Weike Su & Yuanyuan Xie (2007) Y(OTf)3‐Catalyzed, One‐Pot
Synthesis of 1,2,4‐Oxadiazole Derivatives, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 37:24, 4439-4452, DOI: 10.1080/00397910701577695
To link to this article: http://dx.doi.org/10.1080/00397910701577695
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Synthetic Communicationsw, 37: 4439–4452, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701577695
Y(OTf)3-Catalyzed, One-Pot Synthesis of
1,2,4-Oxadiazole Derivatives
Chuanming Yu, Min Lei, Weike Su, and Yuanyuan Xie
Zhejiang Key Laboratory of Pharmaceutical Engineering, College
of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou, China
Abstract: Direct one-step synthesis of 1,2,4-oxadiazole from ketones, nitriles, and
nitric acid is described using yttrium triflate [Y(OTf)3] as the catalyst. The salient
features of this method include a simple procedure, mild condition, easy purification,
and good yields.
Keywords: ketones, nitriles, 1,2,4-oxadiazole derivatives, yttrium triflate
The 1,2,4-oxadiazole derivatives are of significant importance to medicinal
chemistry because they are found in many biologically active compounds.
Publications have reported that substituted 1,2,4-oxadiazole derivatives have
found applications in diverse therapeutic areas including as antikinetoplastid
materials,[1] b3 adrenergic receptor agonists,[2] anti-inflammatory substances,[3]
muscarinic agonists,[4] and serotonineric antagonists.[5]
The widespread interest in 1,2,4-oxadiazole-containing structures has
promoted extensive studies of their synthesis. These include the cycloaddition
of nitrile oxides to amidoximes;[6] treatment of acylated amidoximes with
bases such as NaH, NaOEt, or pyridine;[7] the O-acylation of amidoximes
by an activated carboxylic acid derivative such as ester[5] or acid chlorides
followed by cyclodehydration,[8] the O-acylation of o-vinylbenzamidoxime
Received February 22, 2007
Address correspondence to Weike Su, Zhejiang Key Laboratory of Pharmaceutical
Engineering, College of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou 310014, China. E-mail: leyleem@yahoo.com.cn
4439

4440
C. Yu et al.
and trifluoroacetic anhydride in pyridine;[9] and condensation of nitriles,
hydroxyl amine, and aldehydes under microwave irradiation.[10] Recently,
Itoh and his coworkers reported the one-pot synthesis of 3-acetyl- and
3-benzoyl-1,2,4-oxadiazoles using Fe(NO3)3.[11] However, many of these
processes suffer from limitations such as drastic reaction conditions, low
yields, and tedious workup procedures.
During the past decade, rare-earth-metal triflates have been found to be
unique Lewis acids. They are water-tolerant, reusable catalysts, and they
can effectively promote carbon–carbon and carbon–heteroatom bond
formation in good yields.[12] Because of their unique catalytic properties,
rare-earth-metal triflates have been extensively used for a plethora of
organic reactions. In our most recent work, we investigated the use of
Y(OTf)3 as a catalyst for the preparation of 1,2,4-oxadiazole derivatives.
The reaction of ketones and nitriles with nitric acid in the presence of
Y(OTf)3 gave corresponding 1,2,4-oxadiazole derivatives in good yields
(Scheme 1). Although there are several papers reporting the synthesis of
1,2,4-oxadiazole derivatives, there are few reports in the literature using
ketones, nitriles, and nitric acid as starting materials in the presence of rare-
earth-metal triflates as catalysts.
At first, we carried out the reaction in benzonitrile at 808C, taking a
1:1.1 mol ratio mixture of 4-fluoroacetophenone and nitric acid in the
presence of 5 mol% Y(OTf)3 for 4 hours to afford 3-(4-fluorobenzoyl)-5-
phenyl-1,2,4-oxadiazole in 54% yield (Table 1, entry 8). Encouraged by this
result, we studied different reaction parameters, and the results are summar-
ized in Table 1. Among the various metal triflates such as Cu(OTf)2,
Zn(OTf)2, Mg(OTf)2, Yb(OTf)3, Eu(OTf)3, and Y(OTf)3 studied for this
reaction, Y(OTf)3 was found to be the most effective catalyst in terms of
reaction yields. Then, the reaction was performed in different amounts of
Y(OTf)3.
As shown in Table 1, no reaction was observed when the mixture was
stirred under similar conditions in the absence of Y(OTf)3, even after
heating for 12 h (Table 1, entry 7). Furthermore, we have changed the
amount of Y(OTf)3 from 5 to 30 mol%, finding that the use of 10 mol%
was optimal to ensure high reaction efficiency (85%, yield).
To optimize the temperature for the reaction, we carried out the reaction at
temperatures ranging from 60 to 1108C (Table 2); we found that the yield of
Scheme 1.

1,2,4-Oxadiazole Derivatives
Table 1. Optimization of the reaction conditionsa
4441
Catalyst
(mol%)
Entry
Catalyst
Yieldb,c (%)
1
2
Cu(OTf)2
Zn(OTf)2
Mg(OTf)2
Yb(OTf)3
Eu(OTf)3
Y(OTf)3
None
10
10
10
10
10
10
—
5
62
59
3
31
83
4
5
81
6
85
7
NDd
54
8
Y(OTf)3
Y(OTf)3
Y(OTf)3
Y(OTf)3
9
15
20
30
85
86
10
11
86
aReaction conditions: 4-fluoroacetophenone (0.28 g, 2.0 mmol),
HNO3 (0.15 g, 2.2 mmol, conc. 95%), benzonitrile (1 mL),
reaction temperature 808C, reaction time 4 h.
bIsolated yields based on 4-fluoroacetophenone.
cThe product was 3-(4-fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole.
dNo product was detected.
product improved as the temperature increased from 60 to 808C. The yield
plateaued when the temperature further increased from 90 to 1108C.
Therefore, a reaction of 808C was considered to be most suitable.
Having established the optimized reaction conditions, we then success-
fully synthesized a variety of 1,2,4-oxadiazole derivatives (Scheme 2), and
the results are summarized in Table 3.
Table 2. Optimization of the reaction temperaturea
Temperature
(8C)
Entry
Yieldb,c (%)
1
2
3
4
5
6
60
70
52
74
85
85
86
85
80
90
100
110
aReaction conditions: 4-fluoroacetophenone (0.28 g, 2.0 mmol),
HNO3 (0.15 g, 2.2 mmol, conc. 95%), benzonitrile (1 mL),
reaction time 4 h.
bIsolated yields based on 4-fluoroacetophenone.
cThe product was 3-(4-fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole.

4442
C. Yu et al.
Scheme 2.
As shown in Table 3, acetonitrile (Table 3, entries 1–5), benzonitrile
(Table 3, entries 6–11), and 2-fluorobenzonitrile (Table 3, entries 12–15)
were used in this reaction. We found that the reactivity of acetonitrile was
lower than aromatic nitriles in terms of reaction times and reaction yields.
The reactions were completed within 10–30 h when using acetonitrile as
substrate, much longer than that required for aromatic nitriles (4 h). Further-
more, relative low yields were obtained when using acetonitrile (Table 3,
entries 1–5).
Moreover, several aromatic and aliphatic ketones were examined under the
optimized conditions using 10 mol% of Y(OTf)3. As shown in Table 3, we
found that all the aromatic ketones must carry at least one electron-withdrawing
group such as -Cl, -F, -NO2, otherwise, the reaction could not perform smoothly
to afford the products of 1,2,4-oxadiazoles. We investigated the reaction with
aromatic ketones carrying electron-donating groups, such as acetophenone,
4-methyl-acetophenone, and 4-methoxy-acetophenone; unfortunately, we
obtained the main products of furoxan derivatives, not the 1,2,4-oxadiazole
derivatives that we desired.
A probable mechanism for the reaction may be postulated as shown in
Scheme 3. In this reaction mechanism, the enolization 4 of ketones was accel-
erated by Y(OTf)3, followed by the nitration of ketones. The formation of
nitrile oxides 6 proceeds via the acid-catalyzed dehydration of a-nitroketones
5, and the 1,2,4-oxadiazole derivatives 3 were obtained by the 1,3-dipolar
cycloaddition to nitriles.[11,13]
In conclusion, we have developed an efficient reaction protocal for the
synthesis of 1,2,4-oxadiazole derivatives using ketones, nitriles, and nitric
acid as starting materials in the prence of Y(OTf)3 as a catalyst. The easy
workup procedure, relatively short reaction times, and good yields make
this method a valid contribution to the existing methologies.
EXPERIMENTAL
All reagents were commercial available and used without any purification.
The melting points were recorded on a digital melting-point apparatus
1
WRS-1B and are uncorrected. H and 13C NMR spectra were recorded on a
Varian 400-MHz spectrometer. IR measurements were carried out with

Table 3. Y(OTf)3-catalyzed synthesis of 1,2,4-oxadiazole derivativesa
Time
Entry
Ketones 1
Nitriles 2
(h)
Products
Yieldb (%)
49
1
CH3CN
18
2
3
CH3CN
CH3CN
18
24
47
69
4
5
CH3CN
CH3CN
24
30
73
68
(continued)

Table 3. Continued
Time
(h)
Entry
6
Ketones 1
Nitriles 2
Products
Yieldb (%)
85
4
7
4
83
8
9
4
4
84
82

1,2,4-Oxadiazole Derivatives
4445

Table 3. Continued
Time
(h)
Entry
14
Ketones 1
Nitriles 2
Products
Yieldb (%)
80
4
15
4
81
aReaction conditions: ketones (2.0 mmol), HNO3 (0.15 g, 2.2 mmol, conc. 95%), nitriles (1 mL), reaction temperature 808C, catalyst
Y(OTf)3 10 mol%.
bIsolated yields based on ketones.

1,2,4-Oxadiazole Derivatives
4447
Scheme 3.
Nicolet Aviatar-370 instrument. Mass spectra were measured with a Thermo
Finnigan LCQ-Advantage. Elemental analyses (C, H, N, S) were performed
on a Fisons EA 1110 CHNS elemental analyzer.
General Procedure for the Preparation of 1,2,4-Oxadiazole
Derivatives
A mixture of ketones (1, 2.0 mmol) and HNO3 (0.15 g, 2.2 mmol, conc. 95%)
in nitriles (2, 1 mL) was stirred at 808C in the presence of 10 mol% Y(OTf)3
for the appropriate time (Table 3). After completion of the reaction as
indicated by thin-layer chromatography (TLC), the mixture was diluted
with AcOEt (20 mL) and washed with aq. NaHCO3 solution (10 mL ꢀ 2)
and sat. aq. NaCl (10 mL ꢀ 2). Then the organic phase was dried over
MgSO4 and concentrated in a vacuum. The residue was chromatographed
on silica gel and eluted with petroleum ether–AcOEt (5:1) to give pure
products 3.
Spectral and Analytical Data
3-(4-Fluorobenzoyl)-5-methyl-1,2,4-oxadiazole (3a)
White solid; mp 82–838C. IR (KBr): 1638, 1597, 1481, 1229, 907 cm21. 1H
NMR (400 MHz, CDCl3): d ¼ 8.36–8.39 (m, 2H, ArH), 7.20–7.24 (m, 2H,
ArH), 2.75 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 181.10,
177.62, 167.97, 165.53, 165.40, 133.53, 133.44, 131.34, 116.14, 115.92,
12.35 ppm. MS (EI): m/z (%) ¼ 206 (30) [Mþ]. Anal. calcd. for
C10H7FN2O2: C, 58.26; H, 3.42; N, 13.59. Found C, 58.22; H, 3.40; N, 13.63.
3-(4-Chlorobenzoyl)-5-methyl-1,2,4-oxadiazole (3b)
White solid; mp 108–1108C. IR (KBr): 1682, 1670, 1585, 1208, 911 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.28 (d, 2H, J ¼ 8.0 Hz, ArH), 7.52

4448
C. Yu et al.
(d, 2H, J ¼ 8.0 Hz, ArH), 2.74 (s, 3H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): d ¼ 181.74, 177.99, 165.83, 141.69, 133.58, 132.30, 129.44,
12.68 ppm. MS (EI): m/z (%) ¼ 222 (30), 224 (11) [Mþ]. Anal. calcd. for
C10H7ClN2O2: C, 53.95; H, 3.17; N, 12.58. Found C, 53.99; H, 3.14; N, 12.60.
5-Methyl-3-(3-nitrobenzoyl)-1,2,4-oxadiazole (3c)
Pale yellow crystal; mp 135–1378C. IR (KBr): 1680, 1621, 1533, 1206,
872 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 9.18 (s, 1H, ArH), 8.67
(d, 1H, J ¼ 8.0 Hz, ArH), 8.54 (d, 1H, J ¼ 8.0 Hz, ArH), 7.80 (dd, 1H,
J ¼ 8.0 Hz, ArH), 2.79 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
d ¼ 180.48, 178.12, 165.14, 148.30, 135.90, 134.84, 130.01, 128.56,
125.49, 12.35 ppm. MS (EI): m/z (%) ¼ 233 (30) [Mþ]. Anal. calcd. for
C10H7N3O4: C, 51.51; H, 3.03; N, 18.02. Found C, 51.57; H, 2.99; N, 18.09.
5-Methyl-3-(4-methyl-3-nitrobenzoyl)-1,2,4-oxadiazole (3d)
Yellow crystal; mp 112–1148C. IR (KBr): 1678, 1527, 1345, 1210, 869 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.96 (s, 1H, ArH), 8.46 (d, 1H, J ¼ 8.0 Hz,
ArH), 7.56 (d, 1H, J ¼ 8.0 Hz, ArH), 2.77 (s, 3H, CH3), 2.72 (s, 3H, CH3)
ppm. 13C NMR (100 MHz, CDCl3): d ¼ 180.18, 177.99, 165.25, 149.37,
140.14, 133.98, 133.81, 133.41, 126.94, 30.73, 12.36 ppm. MS (EI): m/z
(%) ¼ 248 (50) [M þ Hþ]. Anal. calcd. for C11H9N3O4: C, 53.44; H, 3.67;
N, 17.00. Found C, 53.38; H, 3.66; N, 16.89.
3-(2,4-Dichloro-5-fluorobenzoyl)-5-methyl-1,2,4-oxadiazole (3e)
White solid; mp 74–758C. IR (KBr): 3034, 1692, 1587, 1255, 852 cm21. 1H
NMR (400 MHz, CDCl3): d ¼ 7.58 (d, 1H, J ¼ 6.4 Hz, ArH), 7.52 (d, 1H,
J ¼ 8.4 Hz, ArH), 2.74 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):
d ¼ 181.42, 178.52, 165.60, 157.70, 155.19, 135.01, 134.96, 132.45,
128.32, 126.35, 126.16, 118.65, 118.40, 12.41 ppm. MS (EI): m/z
(%) ¼ 274 (21) [Mþ]. Anal. calcd. for C10H5Cl2FN2O2: C, 43.67; H, 1.83;
N, 10.18. Found C, 43.60; H, 1.88; N, 10.20.
3-(4-Fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole (3f)
White solid; mp 106–1088C. IR (KBr): 1687, 1600, 1467, 1217, 914 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.43 (dd, 2H, J1 ¼ 5.2 Hz, J2 ¼ 8.4 Hz,
ArH), 8.27 (d, 2H, J ¼ 8.0 Hz, ArH), 7.67 (t, 1H, J ¼ 8.0 Hz, ArH), 7.59
(t, 2H, J ¼ 8.0 Hz, ArH), 7.22–7.26 (m, 2H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): d ¼ 181.33, 176.65, 168.06, 165.50, 166.13, 133.65,
133.56, 131.56, 129.29, 128.54, 123.30, 116.18, 115.96 ppm. MS (EI): m/z
(%) ¼ 268 (25) [Mþ]. Anal. calcd. for C15H9FN2O2: C, 67.16; H, 3.38; N,
10.44. Found C, 67.10; H, 3.44; N, 10.49.

1,2,4-Oxadiazole Derivatives
4449
3-(4-Chlorobenzoyl)-5-phenyl-1,2,4-oxadiazole (3g)
White solid; mp 100–1028C. IR (KBr): 1687, 1561, 1461, 1218, 912 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.34 (d, 2H, J ¼ 8.4 Hz, ArH), 8.29
(d, 2H, J ¼ 7.8 Hz, ArH), 7.68 (t, 1H, J ¼ 7.8 Hz, ArH), 7.60 (t, 2H,
J ¼ 7.8 Hz, ArH), 7.56 (t, 2H, J ¼ 7.8 Hz, ArH) ppm. 13C NMR (100 MHz,
CDCl3): d ¼ 181.72, 176.68, 166.01, 141.42, 133.58, 133.39, 132.08,
129.29, 129.16, 128.53, 123.22 ppm. MS (EI): m/z (%) ¼ 284 (40), 286
(12) [Mþ]. Anal. calcd. for C15H9ClN2O2: C, 63.28; H, 3.19; N, 9.84.
Found C, 63.24; H, 3.22; N, 9.78.
3-(4-Methyl-3-nitrobenzoyl)-5-phenyl-1,2,4-oxadiazole (3h)
Yellowish crystal; mp 107–1098C. IR (KBr): 1656, 1596, 1270, 1164,
897 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 9.04 (s, 1H, ArH), 8.51
(d, 1H, J ¼ 7.6 Hz, ArH), 8.28 (d, 2H, J ¼ 7.6 Hz, ArH), 7.68 (t, 1H,
J ¼ 6.8 Hz, ArH), 7.57–7.62 (m, 3H, ArH), 2.74 (s, 3H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): d ¼ 180.79, 177.28, 166.09, 149.72, 140.55,
134.44, 134.29, 133.78, 129.67, 128.90, 127.43, 123.40, 21.16 ppm. MS
(EI): m/z (%) ¼ 309 (40) [Mþ]. Anal. calcd. for C16H11N3O4: C, 62.14; H,
3.58; N, 13.59. Found C, 62.15; H, 3.66; N, 13.49.
3-(3-Nitrobenzoyl)-5-phenyl-1,2,4-oxadiazole (3i)
Yellowish crystal; mp 123–1258C. IR (KBr): 1683, 1607, 1529, 1346,
1209 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 9.27 (s, 1H, ArH), 8.72
(d, 1H, J ¼ 8.0 Hz, ArH), 8.56 (d, 1H, J ¼ 8.0 Hz, ArH), 8.28 (d, 2H,
J ¼ 8.0 Hz, ArH), 7.80 (t, 1H, J ¼ 8.0 Hz, ArH), 7.69 (t, 1H, J ¼ 8.0 Hz,
ArH), 7.60 (d, 2H, J ¼ 8.0 Hz, ArH) ppm. 13C NMR (100 MHz, CDCl3):
d ¼ 180.75, 177.07, 165.69, 148.41, 136.19, 136.01, 133.79, 130.04,
129.29, 128.63, 128.57, 125.69, 122.99 ppm. MS (EI): m/z (%) ¼ 295 (30)
[Mþ]. Anal. calcd. for C15H9N3O4: C, 61.02; H, 3.07; N, 14.23. Found C,
61.00; H, 3.12; N, 14.19.
3-(2,4-Dichloro-5-fluorobenzoyl)-5-phenyl-1,2,4-oxadiazole (3j)
White solid; mp 121–1238C. IR (KBr): 1697, 1565, 1476, 1256, 1173 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.24 (d, 2H, J ¼ 8.0 Hz, ArH), 7.67 (t, 1H,
J ¼ 8.0 Hz, ArH), 7.56–7.60 (m, 4H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): d ¼ 181.77, 177.46, 166.21, 157.82, 155.31, 135.20, 135.12,
133.75, 132.53, 129.34, 128.56, 128.55, 126.45, 126.26, 123.08, 118.79,
118.55 ppm. MS (EI): m/z (%) ¼ 336 (25), 338 (16) [Mþ]. Anal. calcd. for
C15H7Cl2FN2O2: C, 53.44; H, 2.09; N, 8.31. Found C, 53.40; H, 2.10; N, 8.28.

4450
C. Yu et al.
3-Acetyl-5-phenyl-1,2,4-oxadiazole (3k)
Pale yellow crystal; mp 46–488C. IR (KBr): 2918, 1721, 1560, 1467,
1158 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.23 (d, 2H, J ¼ 7.6 Hz,
ArH), 7.64 (t, 1H, J ¼ 7.6 Hz, ArH), 7.56 (t, 2H, J ¼ 7.6 Hz, ArH), 2.77
(s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 189.02, 177.23,
166.34, 133.05, 129.22, 128.41, 123.27, 27.94 ppm. MS (EI): m/z
(%) ¼ 188 (30) [Mþ]. Anal. calcd. for C10H8N2O2: C, 63.82; H, 4.28; N,
14.89. Found C, 63.77; H, 4.25; N, 14.92.
3-(4-Fluorobenzoyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole (3l)
White solid; mp 114–1168C. IR (KBr): 1673, 1621, 1598, 1470, 1216 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 8.43 (dd, 2H, J1 ¼ 6.0 Hz, J2 ¼ 8.4 Hz,
ArH), 8.28 (t, 1H, J ¼ 7.2 Hz, ArH), 7.66 (dd, 1H, J1 ¼ 7.2 Hz,
J2 ¼ 8.0 Hz, ArH), 7.22–7.39 (m, 4H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): d ¼ 181.08, 173.82, 168.08, 165.52, 165.72, 162.25, 159.65,
125.52, 135.43, 133.66, 133.56, 131.50, 124.90, 117.38, 117.17, 116.20,
115.99 ppm. MS (EI): m/z (%) ¼ 286 (50) [Mþ]. Anal. calcd. for
C15H8F2N2O2: C, 62.94; H, 2.82; N, 9.79. Found C, 63.00; H, 2.77; N, 9.88.
3-(4-Chlorobenzoyl)-5-(2-fluorophenyl)-1,2,4-oxadiazole (3m)
White solid; mp 125–1268C. IR (KBr): 1682, 1620, 1468, 1222, 744 cm21. 1H
NMR (400 MHz, CDCl3): d ¼ 8.32 (d, 2H, J ¼ 8.4 Hz, ArH), 8.26 (t, 1H,
J ¼ 6.8 Hz, ArH), 7.66 (m, 1H, ArH), 7.56 (d, 2H, J ¼ 8.4 Hz, ArH),
7.28–7.38 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 181.37,
173.91, 165.54, 162.16, 159.57, 141.43, 135.52, 135.43, 133.26, 132.02,
131.18, 129.11, 124.85, 117.31, 117.11, 111.84, 111.72 ppm. MS (EI): m/z
(%) ¼ 302 (25) (Mþ). Anal. calcd. for C15H8ClFN2O2: C, 59.52; H, 2.66; N,
9.25. Found C, 59.50; H, 2.58; N, 9.19.
5-(2-Fluorophenyl)-3-(3-nitrobenzoyl)-1,2,4-oxadiazole (3n)
Pale yellow crystal; mp 130–1328C. IR (KBr): 1684, 1620, 1534, 1348,
1211 cm21
.
1H NMR (400 MHz, CDCl3): d ¼ 9.27 (s, 1H, ArH), 8.72
(d, 1H, J ¼ 7.6 Hz, ArH), 8.56 (d, 1H, J ¼ 8.0 Hz, ArH), 8.30 (t, 1H,
J ¼ 7.2 Hz, ArH), 7.80 (t, 1H, J ¼ 7.6 Hz, ArH), 7.69 (m, 1H, ArH), 7.32–
7.41 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3): d ¼ 180.54, 174.27,
165.37, 162.33, 159.73, 148.50, 136.21, 136.01, 135.78, 135.69, 131.29,
130.08, 128.69, 125.71, 125.01, 117.46, 117.26, 111.80, 111.59 ppm. MS
(EI): m/z (%) ¼ 313 (40) [Mþ]. Anal. calcd. for C15H8FN3O4: C, 57.52; H,
2.57; N, 13.41. Found C, 57.48; H, 2.55; N, 13.46.

1,2,4-Oxadiazole Derivatives
4451
5-(2-Fluorophenyl)-3-(4-methyl-3-nitrobenzoyl)-1,2,4-oxadiazole (3o)
Yellow crystal; mp 107–1098C. IR (KBr): 1679, 1618, 1553, 1353,
1
1203 cm21. H NMR (400 MHz, CDCl3): d ¼ 9.03 (s, 1H, ArH), 8.51 (dd,
1H, J1 ¼ 0.8 Hz, J2 ¼ 8.0 Hz, ArH), 8.28 (m, 1H, ArH), 7.67 (m, 1H, ArH),
7.58 (d, 1H, J ¼ 8.4 Hz, ArH), 7.31–7.41 (m, 2H, ArH), 2.73 (s, 3H, CH3)
ppm. 13C NMR (100 MHz, CDCl3): d ¼ 180.12, 174.10, 165.36, 162.27,
159.67, 149.45, 140.24, 135.69, 135.60, 134.09, 133.47, 131.25, 127.03,
124.96, 117.41, 117.21, 111.82, 111.70, 20.76 ppm. MS (EI): m/z
(%) ¼ 327 (25) [Mþ]. Anal. calcd. for C16H10FN3O4: C, 58.72; H, 3.08; N,
12.84. Found C, 58.77; H, 3.05; N, 12.88.
ACKNOWLEDGMENT
We are grateful to the National Basic Research Program (No. 2003CB114402)
and the National Natural Science Foundation of China (No. 20476098).
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