Zirconium(IV) chloride mediated cyclodehydration of 1,2-diacylhydrazines: A convenient synthesis of 2,5-diaryl 1,3,4-oxadiazoles

Article abstract of DOI:10.1081/SCC-120039492

Zirconium(IV) chloride was invented as a mild catalyst for the cyclodehydration of 1,2-diacylhydrazines. Efficient synthesis of several 2,5-disubstituted 1,3,4-oxadiazoles is reported.

Full text of DOI:10.1081/SCC-120039492

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Zirconium(IV) Chloride
Mediated Cyclodehydration
of 1,2‐Diacylhydrazines:
A Convenient Synthesis of
2
,5‐Diaryl 1,3,4‐Oxadiazoles
a a a
G. V. M. Sharma , Asra Begum , Rakesh
&
a
Palakodety Radha Krishna
a
Discovery Laboratory, Organic Chemistry
Division‐III, Indian Institute of Chemical
Technology, Hyderabad, 500 007, India
Published online: 10 Jan 2011.
To cite this article: G. V. M. Sharma , Asra Begum , Rakesh & Palakodety
Radha Krishna (2004) Zirconium(IV) Chloride Mediated Cyclodehydration of
1,2‐Diacylhydrazines: A Convenient Synthesis of 2,5‐Diaryl 1,3,4‐Oxadiazoles,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 34:13, 2387-2391, DOI: 10.1081/SCC-120039492
To link to this article: http://dx.doi.org/10.1081/SCC-120039492
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SYNTHETIC COMMUNICATIONS
Vol. 34, No. 13, pp. 2387–2391, 2004
Zirconium(IV) Chloride Mediated
Cyclodehydration of 1,2-Diacylhydrazines:
A Convenient Synthesis of
,5-Diaryl 1,3,4-Oxadiazoles
#
2
*
G. V. M. Sharma, Asra Begum, Rakesh,
and Palakodety Radha Krishna
Discovery Laboratory, Organic Chemistry Division-III,
Indian Institute of Chemical Technology, Hyderabad, India
ABSTRACT
Zirconium(IV) chloride was invented as a mild catalyst for the cyclo-
dehydration of 1,2-diacylhydrazines. Efficient synthesis of several
2,5-disubstituted 1,3,4-oxadiazoles is reported.
Key Words: Zirconium(IV) chloride; Diacylhydrazines; Cyclization;
,3,4-Oxadiazoles.
1
#
IICT communication no: 030310.
Correspondence: G. V. M. Sharma, Discovery Laboratory, Organic Chemistry Div-
*
ision-III, Indian Institute of Chemical Technology, Hyderabad 500 007, India;
E-mail: esmvee@iict.ap.nic.in.
2
387
DOI: 10.1081/SCC-120039492
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2
388
Sharma et al.
INTRODUCTION
1,3,4-Oxadiazole derivatives, displaying a broad spectrum of biological
activity and a variety of applications in many fields, are compounds of
[1]
general interest. The most common approach towards the preparation of
0
2,5-disubstituted 1,3,4-oxadiazoles consists in cyclodehydration of N,N -
diacylhydrazines promoted by reagents including thionyl chloride, phos-
[2]
[
phorous oxychloride, phosphorous pentoxide, polyphosphoric acid,
3]
[4]
[5]
[6]
and sulfuric acid at elevated temperatures. Though few attempts have
been made to replace these drastic reaction conditions with milder reagents
[
7]
[8]
such as palladium(0) and triphenylphosphine adducts to affect the cycli-
zation, these suffer from the undesired side products. To circumvent such
problems, investigation for efficient and mild reaction conditions for the
synthesis of 1,3,4-oxadiazoles is always warranted.
Herein, in this communication, we wish to report a simple and efficient
method for the synthesis of 1,3,4-oxadiazoles via cyclization of the corres-
ponding diacylhydrazines using zirconium(IV) chloride as the catalyst
(
Sch. 1). Initially, symmetrical diacylhydrazine (entry 1) was treated with
1
3
0 mol% of ZrCl in dichloromethane and acetonitrile independently for
4
hr at room temperature. Being attracted with the better result (71%) in
dichloromethane as solvent, several 1,2-diacylhydrazines bearing a variety
of substituted aromatic rings (Table 1) were prepared and subjected to
cyclodehydration by treatment with 10 mol% of ZrCl . Typically, all the
4
reactions were completed within a shorter time (less than 3 hr) as indicated
by TLC analysis, and the oxadiazoles were obtained in high yields with no
significant byproducts. Interestingly, both aromatic ring deactivating groups
(
entries 4 and 5) and activating groups (entries 6–8) gave good to excellent
yields.
In summary, we have developed a simple and general method for the
synthesis of 1,3,4-oxadiazoles using inexpensive ZrCl as catalyst. Additional
4
advantages over the existing methods include higher yields, shorter reaction
times, and a simple experimental procedure, which makes it a useful process
for the synthesis of 1,3,4-oxadiazoles.
Scheme 1.

ZrCl Mediated Cyclodehydration of 1,2-Diacylhydrazines
4
2389
Table 1. Preparation of 1,3,4-oxadiazoles with substituted aromatic rings.
0
Entry
Ar
Ar
Time (hr)
Yield (%)
1
2
3
4
5
6
7
8
C H
C H
6
3
71
74
88
86
74
75
78
80
6
5
5
5
5
C
C
6
H
H
p-ClC
p-OCH
6
H
4
3
6
3
C
6
H
4
2.5
2.75
3
p-NO C H
2
p-ClC H
6
6
4
4
p-NO
2
C
6
H
4
6 5
C H
p-OCH
p-FC H
3
C
6
H
4
p-OCH
p-FC H
3
C
6
H
4
4
2.5
2.7
2.5
6
4
6
4
p-FC H
6
p-OCH C H
3 6
4
1
Note: All the compounds were characterized by melting points, IR, H-NMR, and
mass spectroscopic analysis.
GENERAL EXPERIMENTAL PROCEDURE
1
The H-NMR spectra were recorded on Varian Gemini 200-MHz
spectrometer using TMS as an internal standard. Mass spectra were recorded
on a VG micromass 70-70H mass spectrometer, and IR spectra were recorded
on Nicolet FT IR-740. In a typical experimental procedure, a stirred solution
0
of N,N -diacylhydrazine (1 mmol) in dichloromethane (10 mL) and ZrCl4
(
0.1 mmol) was added and stirred for 2–3 hr at room temperature. After the
completion of the reaction, reaction mixture was diluted with excess dichloro-
methane and washed with water (10 mL). The organic layer was dried
(
Na SO ) and concentrated under reduced pressure. The crude residue was
2 4
purified by column chromatography (silicagel, Pet.ether–EtOAc) to afford
the 1,3,4-oxadiazoles.
SPECTRAL DATA
21 1
: M.P.: 1378C; IR (KBr): 850, 1260, 1600, 2950, 3190 cm ; H-NMR
1
(
CDCl , 200 MHz): d 7.45–7.65 (m, 6H), 8.10–8.28 (m, 4H); EIMS (m/z, %):
22 (M , 30), 165 (31), 105 (38), 77 (100), 51 (13.7); anal. calcd for
3
þ
2
C H N O: C, 75.66; H, 4.54; found: C, 75.58; H, 4.50; 2: M.P.: 1608C;
1
4 10 2
2
1
1
; H-NMR (CDCl3,
IR (KBr): 925, 1020, 1290, 1425, 1600, 2570 cm
2
2
00 MHz): d 7.41–7.58 (m, 5H), 8.0–8.20 (m, 4H); EIMS (m/z, %);
56 (M , 5), 156 (65), 139 (100), 111 (53), 75 (42.5); anal. calcd for
þ
C H ClN O: C, 65.51; H, 3.53; found: C, 65.48; H, 3.45; 3: M.P.: 1388C;
1
4
9
2
2
1
1
, H-NMR (CDCl3,
IR (KBr): 950, 1025, 1170, 1425, 1600, 2950 cm
3
00 MHz): d 3.80 (s, 3H), 6.95 (d, J ¼ 12.0 HZ, 2H), 7.45 (d, J ¼ 12.0 Hz,

2
390
Sharma et al.
þ
2
7
7
2
7
H), 7.92–8.10 (m, 4H); EIMS (m/z, %): 252 (M , 25), 152 (91), 135 (100),
7 (27), 45 (26); anal. calcd for C H N O : C, 71.42; H, 4.79; found: C,
1
5 12 2 2
1.38; H, 4.70; 4: M.P.: 2198C; IR (KBr): 950, 1025, 1170, 1425, 1600,
2
1 1
950 cm ; H-NMR (CDCl , 200 MHz): d 7.39–7.52 (d, J ¼ 8.6 Hz, 4H),
3
þ
.9–8.05 (d, J ¼ 8.6 Hz, 4H); EIMS (m/z, %): 301 (M , 37), 156 (62), 139
(
found: C, 55.62; H, 2.50; 5: M.P.: 203 C; IR (KBr): 950, 1025, 1170, 1425,
100), 75 (62), 50 (56); anal. calcd for C H ClN O : C, 55.74; H, 2.67;
14 8 3 3
o
2
1
1
1
8
1
600, 2950 cm
;
H-NMR (CDCl , 200 MHz): d 7.40–7.5 (m, 5H),
3
þ
.0–8.2 (d, J ¼ 8.33 Hz, 4H); EIMS (m/z, %); 267 (M , 1.25), 141 (22),
05 (100), 77 (77), 51 (41); anal. calcd for C H N O : C, 62.92; H, 3.39;
4 9 3 3
1
found: C, 62.80; H, 3.30; 6: M.P.: 1608C; IR (KBr): 840, 1020, 1170, 1590,
21 1
910, 3200 cm ; H-NMR (CDCl , 300 MHz): d 3.90 (s, 3H), 6.85–6.95
2
3
(
d, J ¼ 12.2 Hz, 2H), 6.95–7.05 (d, J ¼ 12.2 Hz, 2H), 8.05 (d, J ¼ 12.2 Hz,
þ
4
H); EIMS (m/z, %): 282 (M , 20), 152 (68), 135 (100), 71 (77), 44 (72);
anal. calcd for C H N O : C, 68.07; H, 5.00; found: C, 68.00; H, 4.86; 7:
1
6 14 2 3
2
1
1
; H-NMR
M.P.: 2008C; IR (KBr): 920, 1025, 1280, 1600, 2925 cm
(
CDCl , 300 MHz); d 7.10–7.20 (m, 4H), 8.10–8.20 (m, 4H); EIMS (m/z,
); 258 (M , 6), 140 (100), 123 (73), 95 (51), 75 (22); anal. calcd for
3
þ
%
C H F N O: C, 65.12; H, 3.12; found: C, 65.00; H, 3.02; 8: M.P.: 1058C;
1
4 8 2 2
2
1 1
IR (KBr): 950, 1025, 1425, 1600, 2950 cm ; H-NMR (CDCl , 300 MHz);
3
d 3.90 (s, 3H), 6.80–7.00 (m, 4H), 7.90–8.0 (d, J ¼ 17.6 Hz, 2H), 8.01–
þ
8
.10 (d, J ¼ 17.6 Hz, 2H); EIMS (m/z, %): 270 (M , 25), 152 (61), 135
(
found: C, 66.52; H, 4.02.
100), 92 (13), 77 (20); anal. calcd for C H FN O : C, 66.66; H, 4.10;
15 11 2 2
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Received in the USA March 2, 2004