The reaction of (N-isocyanimino)triphenylphosphorane with benzoic acid derivatives: a novel synthesis of 2-aryl-1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1016/j.tetlet.2007.01.021

The reactions of benzoic acid derivatives with (N-isocyanimino)triphenylphosphorane proceed smoothly at room temperature to afford 2-aryl-1,3,4-oxadiazoles in high yields.

Full text of DOI:10.1016/j.tetlet.2007.01.021

Tetrahedron Letters 48 (2007) 1549–1551
The reaction of (N-isocyanimino)triphenylphosphorane
with benzoic acid derivatives: a novel synthesis
of 2-aryl-1,3,4-oxadiazole derivatives
Ali Souldozi and Ali Ramazani*
Department of Chemistry, The University of Zanjan, PO Box 45195-313, Zanjan, Iran
Received 4 November 2006; revised 19 December 2006; accepted 4 January 2007
Available online 7 January 2007
Abstract—The reactions of benzoic acid derivatives with (N-isocyanimino)triphenylphosphorane proceed smoothly at room temper-
ature to afford 2-aryl-1,3,4-oxadiazoles in high yields.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
ing program to develop efficient and robust methods for
1
9–21
the preparation of heterocyclic compounds,
we
1
,3,4-Oxadiazoles have attracted interest in medicinal
sought to develop a convenient preparation of 2-aryl-
1,3,4-oxadiazoles 5a–g. Herein, we report a hitherto
unknown two-component reaction, which, starting from
simple and readily available benzoic acid derivatives
affords 2-aryl-1,3,4-oxadiazoles 5a–g in a one-pot
reaction with (N-isocyanimino)triphenylphosphorane 2
(Scheme 1).
chemistry as surrogates of carboxylic acids, esters,
and carboxamides. They are an important class of
heterocyclic compounds that have a wide range of
pharmaceutical and biological activities including anti-
microbial, anti-fungal, anti-inflammatory, and anti-
1
–5
hypertensive.
Several methods have been reported in the literature for
the synthesis of 1,3,4-oxadiazoles. These protocols are
2. Results and discussion
6
–11
multi-step in nature.
The most general method
involves the cyclization of diacylhydrazides with a vari-
ety of reagents, such as thionyl chloride, phosphorus
oxychloride or sulfuric acid, usually under harsh reac-
tion conditions. Few reliable and operationally simple
examples have been reported for the one-step synthesis
of 1,3,4-oxadiazoles, especially from readily available
carboxylic acids and acid hydrazides.12–16
The benzoic acid derivative 1 and (N-isocyanimino)tri-
phenylphosphorane 2 in dichloromethane react together
in a 1:1 ratio at room temperature to produce 2-aryl-
1,3,4-oxadiazoles 5 and triphenylphosphine oxide 6
(Scheme 1). The reaction proceeds smoothly and cleanly
under mild conditions and no side reactions were
observed. The mechanism of the reaction between the
benzoic acid derivative 1 and (N-isocyanimino)triphen-
ylphosphorane 2 has not been established experimen-
tally. However, a possible explanation is proposed in
Scheme 1. On the basis of the well established chemistry
In recent years, several methods have been reported for
the preparation of (N-isocyanimino)triphenylphospho-
1
7,18
rane (CNNPPh ) 2 (Scheme 1).
There are several
3
2
2
reports on the use of (N-isocyanimino)triphenylphos-
of isocyanides, it is reasonable to assume that the pro-
tonation of 2 by carboxylic acid 1 followed by quench-
ing of the cationic center by the conjugate base of the
1
7,18
phorane 2 in the synthesis of metal complexes.
How-
ever, the application of 2 in the synthesis of organic
compounds has not been reported. As part of our ongo-
2
3
carboxylic acid can generate iminophosphorane 4.
2
3
Intramolecular aza-Wittig reaction of iminophospho-
rane 4 would lead to the formation of 2-aryl-1,3,4-
oxadiazoles 5 and triphenylphosphine 6 (Scheme 1).
The structures of the products were deduced from their
Keywords: Benzoic acid; (N-Isocyanimino)triphenylphosphorane;
2
*
-Aryl-1,3,4-oxadiazole; Aza-Wittig reaction.
Corresponding author. Tel.: +98 241 5152572; fax: +98 241
1
13
5283100; e-mail: aliramazani@yahoo.com
IR, H NMR and C NMR spectra. The mass spectra
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.01.021

1550
A. Souldozi, A. Ramazani / Tetrahedron Letters 48 (2007) 1549–1551
O
X
Y
_
+
OH
CH Cl2
+
2
C
N
N
PPh3
r. t.
1
2
Ph P
3
N
O
_
O
+
N
X
Y
N
HC
N
PPh3
O
X
Y
H
O
3
4
1
, 3, 4, 5
X
Y
a
b
c
d
e
f
H
Br
H
Cl
H
Me
H
H
Br
H
Cl
H
X
N
N
+
Ph PO
O
H
3
Y
g
H
Me
5
6
Scheme 1.
of these compounds displayed molecular ion peaks at
the appropriate m/z values.
(CDCl , 250 MHz): dH 8.42 (s, 1H, oxadiazole); 8.11–
3
13
8.05 (m, 2H, arom); 7.59–7.48 (m, 3H, arom).
C
NMR (CDCl , 62.5 MHz): d 164.79 (1C, oxadiazole);
3
C
1
52.67 (1CH, oxadiazole); 132.03, 129.13, and 127.10
3
. Conclusions
(5CH, arom), 123.42 (1C, arom). Anal. Calcd for
C H N O (146): C, 65.75; H, 4.14; N, 19.17. Found:
C, 65.70; H, 4.39; N, 19.11. MS (EI) (m/z): 146 (M ).
8
6
2
+
We believe that the reported method offers a mild, sim-
ple, and efficient route for the preparation of 2-aryl-
1
,3,4-oxadiazole derivatives. Its ease of work-up, high
4.2. 2-(3-Bromophenyl)-1,3,4-oxadiazole 5b
yields and fairly mild reaction conditions make it a use-
ful addition to modern synthetic methodologies. Other
aspects of this process are under investigation.
White crystals; mp: 80.1 °C; Yield: 91%. IR (KBr) (mmax,
À1
1
cm ): 3092, 2923, 1653, 1553, 1115, 730. H NMR
(
CDCl , 250 MHz): dH 8.50 (s,1H, oxadiazole); 8.24–
3
8
.23 (m, 1H, arom); 8.04–8.01 (m, 1H, arom); 7.72–
1
3
4. General procedure
7.67 (m, 1H, arom); 7.44–7.34 (m, 1H, arom).
C
NMR (CDCl , 62.5 MHz): d 163.53 (1C, oxadiazole);
3
C
To a magnetically stirred solution of (N-isocyan-
152.87 (1CH, oxadiazole); 125.25 and 123.14 (2C,
arom); 135.01, 130.73, 129.96, and 125.63 (4CH, arom).
1
7
imino)triphenylphosphorane 2 (0.302 g, 1 mmol) in
CH Cl (8 ml) was added dropwise a solution of 1
Anal. Calcd for C
H BrN O (225): C, 42.70; H, 2.24;
5 2
2
2
8
(
1 mmol) in CH Cl (7 ml) over 15 min. The mixture
N, 12.45. Found: C, 42.64; H, 2.29; N, 12.53. MS (EI)
(m/z): 226 ((M+2) ), 224 (M ).
2 2
+
+
was stirred for 12 h at room temperature. The solvent
was removed under reduced pressure and the viscous
residue was purified by flash column chromatography
4.3. 2-(4-Bromophenyl)-1,3,4-oxadiazole 5c
(
silica gel; petroleum ether–ethyl acetate (8:1)). The sol-
vent was removed under reduced pressure and the prod-
ucts (5a–g) were obtained. The characterization data of
the compounds are given below.
White crystals; mp: 140.2 °C; Yield: 92%. IR (KBr)
À1
(m , cm ): 3146, 3092, 2930, 1600, 1477, 1108, 831.
max
1
H NMR (CDCl , 250 MHz): dH 8.47 (s, 1H, oxadiaz-
3
ole); 7.98–7.87 (m, 2H, arom); 7.70–7.50 (m, 2H, arom).
1
3
4
.1. 2-Phenyl-1,3,4-oxadiazole 5a
C NMR (CDCl , 62.5 MHz): d 164.11 (1C, oxadiaz-
3 C
ole); 152.74 (1CH, oxadiazole), 126.82 and 122.35 (2C,
arom), 131.83 and 128.51 (4CH, arom). Anal. Calcd
for C H BrN O (225): C, 42.70; H, 2.24; N, 12.45.
White crystals; mp: 143.6 °C; Yield: 91%. IR (KBr)
À1
1
(
m
, cm ): 3008, 1692, 1661, 1530, 723. H NMR
max
8
5
2

A. Souldozi, A. Ramazani / Tetrahedron Letters 48 (2007) 1549–1551
1551
Found: C, 42.56; H, 2.17; N, 12.39. MS (EI) (m/z): 226
Acknowledgment
+
+
(
(M+2) ), 224 (M ).
.4. 2-(3-Chlorophenyl)-1,3,4-oxadiazole 5d
White crystals; mp: 115.3 °C; Yield: 86%. IR (KBr) (mmax,
This work was supported by the ‘Sandoogh Hemayate
as Pajuoheshgharane Keshvare Iran’.
4
À1
1
cm ): 3031, 2923, 1554, 1123, 777. H NMR (CDCl ,
3
References and notes
2
1
50 MHz): dH 8.50 (s, 1H, oxadiazole); 8.05–7.95 (m,
H, arom); 7.86–7.78 (m, 1H, arom), 7.58–7.44 (m, 2H,
1
. Tully, W. R.; Gardner, C. R.; Gillespie, R. J.; Westwood,
R. J. Med. Chem. 1991, 34, 2060–2067.
. Chen, C.; Senanayake, C. H.; Bill, T. J.; Larsen, R. D.;
Verhoeven, T. R.; Reider, P. J. J. Org. Chem. 1994, 59,
3738–3741.
1
3
arom). C NMR (CDCl , 62.5 MHz): dC 163.17 (1C,
3
oxadiazole), 152.84 (1CH, oxadiazole), 135.28 and
2
1
25.07 (2C, arom), 132.09, 130.52, 127.11, and 125.20
(
4CH, arom). Anal. Calcd for C H ClN O (180.5): C,
8
5
2
5
1
3.21; H, 2.79; N, 15.51. Found: C, 53.29; H, 2.85; N,
5.45. MS (EI) (m/z): 182 ((M+2) ), 180 (M ).
3. Holla, B. S.; Gonsalves, R.; Shenoy, S. Eur. J. Med. Chem.
2000, 35, 267–271.
+
+
4
5
6
. Crimmin, M. J.; O’Hanlon, P. J.; Rogers, N. H.; Walker,
G. J. Chem. Soc., Perkin Trans. 1 1989, 2047–2056.
. Laddi, U. V.; Desai, S. R.; Bennur, R. S.; Bennur, S. C.
Ind. J. Heterocycl. Chem. 2002, 11, 319–322.
. For some recent examples, see: Baxendale, I. R.; Ley, S.
V.; Martinelli, M. Tetrahedron 2005, 61, 5323–5349.
4
.5. 2-(4-Chlorophenyl)-1,3,4-oxadiazole 5e
White crystals; mp: 127.1–128.4 °C; Yield: 83%. IR
À1
(
KBr) (m , cm ): 3077, 1608, 1485, 1092, 838, 738.
H NMR (CDCl , 250 MHz): d 8.49 (s, 1H, oxadiaz-
max
1
3
H
7. Liras, S.; Allen, M. P.; Segelstein, B. E. Synth. Commun.
2000, 30, 437–443.
8. Brown, B. J.; Clemens, I. R.; Neesom, J. K. Synlett 2000,
1, 131–133.
9. Coppo, F. T.; Evans, K. A.; Graybill, T. L.; Burton, G.
Tetrahedron Lett. 2004, 45, 3257–3260.
3
ole); 8.03 (d, 2H, J = 8.4 Hz, arom); 7.50 (d, 2H,
HH
3
13
JHH = 8.4 Hz, arom). C NMR (CDCl , 62.5 MHz):
3
dC 164.01 (1C, oxadiazole), 152.73 (1CH, oxadiazole),
38.36 and 121.92 (2C, arom); 129.55 and 128.38
4CH, arom). Anal. Calcd for C H ClN O (180.5): C,
1
(
8
5
2
1
0. Brain, C. T.; Paul, J. M.; Loong, Y.; Oakley, P. J.
Tetrahedron Lett. 1999, 40, 3275–3278.
5
1
3.21; H, 2.79; N, 15.51. Found: C, 53.15; H, 2.84; N,
5.46. MS (EI) (m/z): 182 ((M+2) ), 180 (M ).
+
+
1
1
1. Brain, C. T.; Brunton, S. A. Synlett 2001, 3, 382–384.
2. Tandon, V. K.; Chhor, R. B. Synth. Commun. 2001, 31,
4
.6. 2-m-Tolyl-1,3,4-oxadiazole 5f
1
727–1732.
1
3. Mashraqui, S. H.; Ghadigaonkar, S. G.; Kenny, R. S.
White crystals; mp: 64.4 °C; Yield: 92%. IR (KBr) (m
,
max
1
Synth. Commun. 2003, 33, 2541–2545.
À1
cm ): 3108, 2985, 2408, 2277, 1554, 1500, 1115, 731. H
14. Bentiss, F.; Lagrenee, M.; Barbry, D. Synth. Commun.
2001, 31, 935–938.
15. Jedlovska, E.; Lesko, J. Synth. Commun. 1994, 24, 1879–
NMR (CDCl , 250 MHz): dH 8.46 (s, 1H, oxadiazole);
3
7
2
1
1
1
.90–7.80 (m, 2H, arom); 7.43–7.31 (m, 2H, arom);
1
3
1
885.
6. Wang, Y.; Sauer, D. R.; Djuric, S. W. Tetrahedron Lett.
006, 47, 105–108.
.43 (s, 3H, CH3). C NMR (CDCl , 62.5 MHz): dC
3
1
1
64.90 (1C, oxadiazole); 152.56 (1CH, oxadiazole);
32.80, 129.01, 127.61, 124.21 (4CH, arom); 139.02,
2
7. Stolzenberg, H.; Weinberger, B.; Fehlhammer, W. P.;
23.33 (2C, arom); 21.32 (1C, CH ). Anal. Calcd for
3
P u¨ hlhofer, F. G.; Weiss, R. Eur. J. Inorg. Chem. 2005, 21,
C H N O (160): C, 67.49; H, 5.03; N, 17.49. Found:
9
8
2
4
263–4271.
+
C, 67.42; H, 5.11; N, 17.43 . MS (EI) (m/z): 160 (M ).
1
8. Chiu, T. W.; Liu, Y. H.; Chi, K. M.; Wen, Y. S.; Lu, K. L.
Inorg. Chem. 2005, 44, 6425–6430.
4
.7. 2-p-Tolyl-1,3,4-oxadiazole 5g
19. Yavari, I.; Ramazani, A.; Yahya-Zadeh, A. Synth. Com-
mun. 1996, 26, 4495–4499.
White crystals; mp: 86.9 °C; Yield: 93%. IR (KBr) (m
,
20. Ramazani, A.; Ahmadi, E.; Kazemizadeh, A. R.; Dolaty-
ari, L.; Noshiranzadeh, N.; Eskandari, I.; Souldozi, A.
Phosphorus, Sulphur, Silicon Relat. Elem. 2005, 180, 2419–
max
1
À1
cm ): 3123, 2915, 1615, 1500, 1100, 954, 831, 738. H
NMR (CDCl , 250 MHz): dH 8.44 (s, 1H, oxadiazole),
3
2
422.
7
2
1
1
.99–7.83 (m, 2H, arom), 7.34–7.18 (m, 2H, arom),
1
3
21. Ramazani, A.; Ahmadi, E. Phosphorus, Sulfur, Silicon
Relat. Elem. 2006, 181, 2725–2729.
.43 (s, 3H, CH3). C NMR (CDCl , 62.5 MHz): dC
3
64.89 (1C, oxadiazole); 152.37 (1CH, oxadiazole);
42.58 and 120.70 (2C, arom), 129.81 and 127.03
2
2. Shaabani, A.; Soleimani, E.; Khavasi, H. R.; Hoffmann,
R.-D.; Rodewald, U. Ch.; Pottgen, R. Tetrahedron Lett.
2006, 47, 5493–5496.
(
4CH, arom), 21.65 (1C, CH ). Anal. Calcd for
3
C H N O (160): C, 67.49; H, 5.03; N, 17.49. Found:
C, 67.55; H, 5.09; N, 17.43. MS (EI) (m/z): 160 (M ).
23. Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197–
9
8
2
+
1218.