An efficient three-component synthesis of 3-(5-alkyl/aryl-1,3,4-oxadiazol- 2-yl)-3-hydroxy-1,3-dihydro-2 H -indol-2-ones

Article abstract of DOI:10.1055/s-0030-1258300

An efficient three-component synthesis of 3-(1,3,4-oxadiazol-2-yl)-3- hydroxy-1,3-dihydro-2H-indol-2-ones is described. A mixture of N-isocyaniminotriphenylphosphorane, an isatin, and a carboxylic acid undergoes a 1:1:1 addition reaction under mild condit

Full text of DOI:10.1055/s-0030-1258300

4082
PAPER
An Efficient Three-Component Synthesis of 3-(5-Alkyl/aryl-1,3,4-oxadiazol-
2-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-ones
T
hree-Component Syn
e
thesis of 1,3
h
,4-Oxadiaz
od
les i Adib,*a Ehsan Sheikhi,a Azadeh Kavoosi,a Hamid Reza Bijanzadehb
a
School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155–6455, Tehran, Iran
Fax +98(21)66495291; E-mail: madib@khayam.ut.ac.ir
b
Department of Chemistry, Tarbiat Modarres University, P. O. Box 14115–175, Tehran, Iran
Received 26 August 2010
have been described.11 Some indole derivatives have been
shown to possess antibacterial,12 antitumor,13 antiviral14
and anti-inflammatory15 properties.
Abstract: An efficient three-component synthesis of 3-(1,3,4-oxa-
diazol-2-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-ones is described.
A mixture of N-isocyaniminotriphenylphosphorane, an isatin, and a
carboxylic acid undergoes a 1:1:1 addition reaction under mild con-
ditions to afford the title compounds in excellent yields.
So far, the most common synthetic methods reported for
the preparation of 1,3,4-oxadiazoles involve: (i) transfor-
mation of an existing heterocycle and (ii) cyclizations.
Cyclizations may represent either a single bond forma-
tion: cyclodehydration of 1,2-diacylhydrazines, oxidative
cyclization of acylhydrazones, cyclodesulfurization of
thiosemicarbazides, or formation of two bonds: condensa-
tion and then cyclization of hydrazides with carboxylic
acids, acyl chlorides, esters, amides, trialkyl orthoesters,
carbon disulfide or other C–S containing components,
cyanogen bromide, potassium isocyanate, trichloro-
methylarenes, and imidoyl chlorides, among other ap-
proaches.2,3,16
Key words: N-isocyaniminotriphenylphosphorane, isatins, carbox-
ylic acids, 1,3,4-oxadiazoles, multi-component reactions, heterocy-
cles, cyclizations
Multi-component reactions (MCRs) have emerged as an
efficient and powerful tool in modern synthetic organic
chemistry due to their valued features such as atom econ-
omy, straightforward reaction design, and the opportunity
to construct target compounds by the introduction of sev-
eral diversity elements in a single chemical event. Typi-
cally, purification of products resulting from MCRs is
also simple since all the organic reagents employed are
consumed and are incorporated into the target compound.1
MCRs, leading to interesting heterocyclic scaffolds, are
particularly useful for the construction of diverse chemi-
cal libraries of ‘drug-like’ molecules. The isocyanide-
based MCRs are especially important in this area.1d,e
As far as we know there is only one report in the literature
on the synthesis of 3-hydroxy-3-(1,3,4-oxadiazol-2-yl)-
1,3-dihydro-2H-indol-2-ones. Very recently, Pervak et al.
used trimethylsilyl-1,3,4-oxadiazole as a synthon for the
synthesis of these compounds.17 Heating a mixture of tri-
methylsilyl-1,3,4-oxadiazole and an isatin in KF/dibenzo-
18-crown-6 system in boiling toluene or xylene led to the
corresponding trimethylsilyl ether intermediate, which
was converted into 3-hydroxy-3-(1,3,4-oxadiazol-2-yl)-
1,3-dihydro-2H-indol-2-ones on treatment with RbF.
During recent years there has been considerable investiga-
tion on different classes of oxadiazoles. In particular,
compounds containing 1,3,4-oxadiazole nucleus have
been shown to possess a wide range of pharmacological
and therapeutic activities. Some 1,3,4-oxadiazoles have
exhibited analgesic, anti-inflammatory, anticonvulsant,
tranquilizing, myorelaxant, antidepressant, vasodilatato-
ry, diuretic, antiulcer, antiarythmic, antiserotoninic, spas-
molytic, hypotensive, antibronchocontrictive, anticho-
linergic, and antiemetic activities. Furthermore, many
1,3,4-oxadiazole derivatives have been reported as active
inhibitors of several enzymes.2,3
There are several reports on the use of N-isocyanimino-
triphenylphosphorane (Ph3PNNC, 1) (Scheme 1) in the
synthesis of metal complexes.18,19 However, applications
of 1 in organic synthesis are rare. Recently, synthesis of
1,3,4-oxadiazepines20 and 2-aryl-1,3,4-oxadiazoles21
were reported using N-isocyaniminotriphenylphospho-
rane (1) in MCRs.
As part of our current studies on the design of new routes
for the preparation of biologically active heterocyclic
compounds,22 very recently, we have described the
synthesis of 2-aryl-5-hydroxyalkyl-1,3,4-oxadiazoles,23a
3-(1-hydroxyalkyl)[1,2,4]triazolo[4,3-c]quinazolines,23b
and 3-aryl-1-(arylmethylideneamino)pyrrolidine-2,5-di-
ones23c by use of 1 in MCRs. Herein we wish to report a
new synthesis of 3-hydroxy-3-(1,3,4-oxadiazol-2-yl)-1,3-
dihydro-2H-indol-2-ones. Thus, a mixture of N-isocyan-
iminotriphenylphosphorane (1), an isatin 2, and a carbox-
ylic acid 3 undergoes a 1:1:1 addition reaction in CH2Cl2
at ambient temperature to produce the corresponding 3-
(5-alkyl/aryl-1,3,4-oxadiazol-2-yl)-3-hydroxy-1,3-dihy-
Differently substituted 1,3,4-oxadiazoles have potential
applications as photosensitizers,4 liquid crystals,5 ionic
liquid solvents6 and organic light-emitting devices.7 Some
of them also have photomechanic,8 photoluminescent, and
electrochromic properties.9,10
A huge number of synthetic or semi-synthetic indoles
with significant biological or pharmacological activities
SYNTHESIS 2010, No. 23, pp 4082–4086
x
x.
x
x
.
2
0
1
0
Advanced online publication: 14.10.2010
DOI: 10.1055/s-0030-1258300; Art ID: P13310SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Three-Component Synthesis of 1,3,4-Oxadiazoles
4083
X
O
N
N
X
HO
O
CH2Cl2
RCO2H
Ph3PO
Ph3PNNC
O
+
+
+
R
O
r.t., 12 h
N
NH
H
1
2
3
4
Scheme 1 One-pot three-component synthesis of 3-(5-alkyl/aryyl-1,3,4-oxadiazol-2-yl)-3-hydroxy-1,3-dihydro-2H-indol-2-ones 4
dro-2H-indol-2-ones 4a–h in 92–98% yields (Scheme 1, formation of the corresponding 3-(1,3,4-oxadiazol-2-yl)-
Table 1).
3-hydroxy-1,3-dihydro-2H-indol-2-ones 4. Any product
other than 4 and triphenylphosphine oxide could not be
detected by NMR spectroscopy.
All the reactions went to completion within 12 hours. 1H
NMR analysis of the reaction mixtures clearly indicated
The structures of the isolated products 4 were confirmed
1
on the basis of IR, H and 13C NMR spectroscopy, mass
Table 1 1,3,4-Oxadiazoles 4a–h
spectrometry, and elemental analysis. The IR spectrum of
4a showed absorptions at 3312, 3214 and 1711 cm–1 indi-
cating the presence of amide NH, hydroxy, and carbonyl
functionalities. The mass spectrum of 4a displayed the
molecular ion (M+) peak at m/z = 293, which was consis-
tent with the 1:1:1 adduct of N-isocyaniminotriphe-
nylphosphorane, benzoic acid, and isatin with the loss of
4
a
R
X
H
Yield (%)a
96
b
H
96
Cl
1
triphenylphosphine oxide. The H NMR spectrum of 4a
exhibited two fairly sharp signals due to OH (d = 7.65)
and NH (d = 10.80) groups, as well as characteristic sig-
nals for the nine H atoms of the phenyl and phenylene
moieties in the aromatic region of the spectrum. The 1H-
decoupled 13C NMR spectrum of 4a showed a distinct res-
onance at d = 72.56 due to COH group along with three
deshielded characteristic resonances at d = 164.63 and
164.70 for the two oxadiazole carbon atoms, and
d = 173.64 due to the carbonyl group as well as other ten
signals for the aromatic carbon atoms (7 CH and 3 C) in
agreement with the proposed structure.
c
H
H
98
95
d
S
e
NO2
94
N
f
NO2
NO2
NO2
97
92
93
A mechanistic rationalization for this reaction is provided
in Scheme 2. On the basis of the well-established chemis-
try of isocyanides,1d,e,24–26 it is reasonable to assume that
the first step could involve nucleophilic addition of the
isocyanide 1 on the isatin 2 and subsequent protonation of
the alkoxide intermediate 5 by the acid 3, leading to the ni-
trilium intermediate 6. This intermediate may be attacked
g
h
a Isolated yields.
O
O
_
O
HO
R
_
C
+
+
3
N
N
Ph3P
O
Ph3P
N
N
NH
N
H
O
5
1
2
+
Ph3P
Ph3P
_
O
HO
N
N
N
N
O
HO
HO
4
+
O
R
Ph3P
N
N
NH
– Ph3PO
O
R
NH
NH
O
6
O
O
O
8
9
_
O
R
7
Scheme 2 Proposed mechanism for the reaction
Synthesis 2010, No. 23, 4082–4086 © Thieme Stuttgart · New York

4084
M. Adib et al.
PAPER
3-[5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl]-3-hydroxy-1,3-di-
hydro-2H-indol-2-one (4b)
Yield: 0.31 g (96%); light pink crystals; mp 236 °C.
by the conjugate base of the acid 7 to form the adduct 8.
This adduct may undergo intramolecular aza-Wittig reac-
tion of the iminophosphorane moiety with the ester carbo-
nyl to afford the isolated 3-(1,3,4-oxadiazol-2-yl)-3-
hydroxy-1,3-dihydro-2H-indol-2-ones 4 by removal of
triphenylphosphine oxide from the betaine intermediate 9.
IR (KBr): 3320 (OH), 3189 (NH), 1703 (C=O), 1606, 1545, 1470,
1403, 1347, 1280, 1239, 1185, 1127, 1078, 1009, 952, 929, 877,
829, 738 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 6.92 (d, J = 7.7 Hz, 1 H,
CH), 7.04 (t, J = 7.5 Hz, 1 H, CH), 7.33 (t, J = 7.8 Hz, 1 H, CH),
7.46 (d, J = 7.4 Hz, 1 H, CH), 7.65 (s, 1 H, OH), 7.68 (d, J = 8.6 Hz,
2 H, 2 × CH), 8.00 (d, J = 8.6 Hz, 2 H, 2 × CH), 10.80 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.56 (COH), 110.42 (CH),
121.80 (C), 122.40 and 125.46 (2 × CH), 128.32 (C), 128.47 and
129.69 (2 × CH), 130.71 (CH), 137.04 and 141.95 (2 × C), 163.99
and 164.81 (2 × OC=N), 173.58 (C=O).
EI-MS: m/z (%) = 329 (2, [M+ 37Cl]), 327 (8, [M+ 35Cl]), 293 (24),
279 (20), 236 (16), 191 (11), 167 (31), 149 (100), 97 (28), 83 (31),
77 (11), 69 (36), 57(96), 43 (40).
In summary, we have developed a one-pot three-compo-
nent reaction between N-isocyaniminotriphenylphospho-
rane (1), isatins 2 and carboxylic acids 3 for the
preparation of 3-(5-alkyl/aryl-1,3,4-oxadiazol-2-yl)-3-hy-
droxy-1,3-dihydro-2H-indol-2-ones 4, which are of po-
tential synthetic and pharmacological interest. Mild
reaction conditions and excellent yields of the products
are the main advantages of this method. The reactions
were performed under neutral conditions, and the starting
materials and reagents have been mixed without any acti-
vation or modification. The simplicity of this method
makes it an interesting alternative to other 1,3,4-oxadia-
zole syntheses. 3-(1,3,4-Oxadiazol-2-yl)-3-hydroxy-2H-
indol-2-ones prepared in the present study may find useful
applications in synthetic organic, bioorganic, and medici-
nal chemistry.
Anal. Calcd for C16H10ClN3O3 (327.72): C, 58.64; H, 3.08; N,
12.82. Found: C, 58.5; H, 3.2; N, 12.7.
3-Hydroxy-3-[5-(2-naphthyl)-1,3,4-oxadiazol-2-yl]-1,3-dihy-
dro-2H-indol-2-one (4c)
Yield: 0.33 g (98%); light pink crystals; mp 273–274 °C.
IR (KBr): 3158 (NH), 3118 (OH), 1725 (C=O), 1616, 1537, 1467,
1381, 1329, 1234, 1184, 1115, 1073, 1031, 994, 917, 865, 810, 747,
661 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 6.97 (d, J = 7.8 Hz, 1 H,
CH), 7.07 (t, J = 7.5 Hz, 1 H, CH), 7.35 (t, J = 7.7 Hz, 1 H, CH),
7.55 (d, J = 7.4 Hz, 1 H, CH), 7.58–7.65 (m, 2 H, 2 × CH), 7.75 (s,
1 H, OH), 7.98 (d, J = 7.6 Hz, 1 H, CH), 8.05 (d, J = 8.5 Hz, 1 H,
CH), 8.09 (d, J = 8.5 Hz, 1 H, CH), 8.14 (d, J = 7.5 Hz, 1 H, CH),
8.61 (s, 1 H, CH), 10.88 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.70 (COH), 110.51 (CH),
120.24 (C), 122.49, 122.77, 125.56, 127.13, 127.35, 127.87 and
128.33 (7 × CH), 128.49 (C), 128.95, 129.33 and 130.76 (3 × CH)
132.41, 134.30 and 142.05 (3 × C), 164.81 and 165.00 (2 × OC=N),
173.79 (C=O).
All the chemicals were obtained from Merck (Germany), and were
used without further purification. Melting points were measured on
an Electrothermal 9100 apparatus and are uncorrected. Elemental
analyses for C, H, and N were performed using a Heraeus CHN-O-
Rapid analyzer. Mass spectra were recorded on an Agilent Technol-
ogies (HP) 5973 mass spectrometer operating at an ionization po-
tential of 20 eV. 1H and 13C NMR spectra were measured (DMSO-
d6 solution) with a Bruker DRX-500 Avance spectrometer at 500.1
and 125.8 MHz, respectively. IR spectra were recorded on a
Shimadzu IR–460 spectrometer. Chromatography columns were
prepared from Merck silica gel 60.
1,3,4-Oxadiazoles 4a–h; General Procedure
EI-MS: m/z (%) = 343 (100, [M+]), 314 (7), 287 (14), 230 (5), 195
(10), 153 (94), 146 (20), 127 (35), 119 (39), 92 (18), 77 (9), 65 (9).
A mixture of N-isocyaniminotriphenylphosphorane (1; 302 mg, 1
mmol), an appropriate isatin 2 (1 mmol), and an appropriate carbox-
ylic acid 3 (1 mmol) in CH2Cl2 (4 mL) was stirred at r.t. for 12 h.
Then, the solvent was removed and the residue was purified by col-
umn chromatography using n-hexane–EtOAc (4:1) as eluent. The
solvent was removed to afford the product (Table 1).
Anal. Calcd for C20H13N3O3 (343.34): C, 69.96; H, 3.82; N,12.24.
Found: C, 69.9; H, 3.8; N, 12.3.
3-{5-[(Benzylsulfanyl)methyl]-1,3,4-oxadiazol-2-yl}-3-hydroxy-
1,3-dihydro-2H-indol-2-one (4d)
Yield: 0.33 g (95%); light pink crystals; mp 178 °C.
3-Hydroxy-3-(5-phenyl-1,3,4-oxadiazol-2-yl)-1,3-dihydro-2H-
indol-2-one (4a)
Yield: 0.28 g (96%); light pink crystals; mp 234 °C.
IR (KBr): 3310 (NH), 3287 (OH), 1709 (C=O), 1615, 1572, 1463,
1409, 1352, 1186, 1125, 1082, 1033, 992, 924, 754, 700 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 3.77 and 3.88 (2 s, 4 H,
2 × CH2), 6.93 (d, J = 7.7 Hz, 1 H, CH), 7.04 (t, J = 7.6 Hz, 1 H,
CH), 7.24 (t, J = 7.0 Hz, 1 H, CH), 7.26–7.33 (m, 5 H, 5 × CH), 7.36
(d, J = 7.4 Hz, 1 H, CH), 7.60 (s, 1 H, OH), 10.80 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 23.47 and 35.12 (2 × CH2),
72.62 (COH), 110.45, 122.39, 125.26 and 127.17 (4 × CH), 128.45
(C), 128.49, 128.97 and 130.71 (3 × CH), 137.09 and 141.94
(2 × C), 164.89 and 165.30 (2 × OC=N), 173.67 (C=O).
EI-MS: m/z (%) = 353 (<1, [M+]), 291 (12), 263 (9), 231 (92), 213
(10), 206 (7), 181 (8), 161 (11), 147 (24), 119 (43), 123 (44), 91
(100), 84 (56), 77 (13), 65 (24).
IR (KBr): 3312 (NH), 3214 (OH), 1711 (C=O), 1611, 1550, 1462,
1368, 1229, 1238, 1183, 1118, 1074, 1020, 925, 759 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 6.92 (d, J = 7.7 Hz, 1 H,
CH), 7.04 (t, J = 7.5 Hz, 1 H, CH), 7.33 (t, J = 7.7 Hz, 1 H, CH),
7.46 (d, J = 7.4 Hz, 1 H, CH), 7.58–7.64 (m, 3 H, 3 × CH), 7.65 (s,
1 H, OH), 10.80 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.56 (COH), 110.39 (CH),
122.37 (CH), 122.90 (C), 125.40 and 126.61 (2 × CH), 128.38 (C),
129.47, 130.66 and 132.24 (3 × CH), 141.93 (C), 164.63 and 164.70
(2 × OC=N), 173.64 (C=O).
EI-MS: m/z (%) = 293 (15, [M+]), 279 (13), 266 (9), 229 (9), 191
(10), 167 (22), 149 (86), 112 (15), 97 (18), 83 (27), 77 (15), 69 (66),
57 (69), 43 (100).
Anal. Calcd for C18H15N3O3S (353.40): C, 61.18; H, 4.28; N, 11.89.
Found: C, 61.2; H, 4.3; N, 11.9.
Anal. Calcd for C16H11N303 (293.28): C, 65.53; H, 3.78; N, 14.33.
Found: C, 65.7; H, 3.8; N, 14.1.
Synthesis 2010, No. 23, 4082–4086 © Thieme Stuttgart · New York

PAPER
Three-Component Synthesis of 1,3,4-Oxadiazoles
4085
3-[5-(9-Anthryl)-1,3,4-oxadiazol-2-yl]-3-hydroxy-5-nitro-1,3-
dihydro-2H-indol-2-one (4e)
Anal. Calcd for C18H12N4O5 (364.32): C, 59.34; H, 3.32; N, 15.38.
Found: C, 59.5; H, 3.4; N, 15.2.
Yield: 0.41 g (94%); pale brown powder; mp 272–273 °C.
3-Hydroxy-3-[5-(2-naphthyl)-1,3,4-oxadiazol-2-yl]-5-nitro-1,3-
dihydro-2H-indol-2-one (4h)
Yield: 0.36 g (93%); pale brown powder; mp 269–270 °C.
IR (KBr): 3152 (NH), 3097 (OH), 1755 (C=O), 1617, 1531, 1461,
1404, 1331, 1244, 1186, 1106, 1012, 935, 899, 837, 782, 737, 687
cm–1.
IR (KBr): 3158 (NH), 3091 (OH), 1734 (C=O), 1615, 1526, 1455,
1404, 1341, 1290, 1232, 1190, 1123, 1068, 972, 940, 888, 829, 782,
740, 702 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 7.17 (d, J = 8.5 Hz, 1 H,
CH), 7.60–7.70 (m, 2 H, 2 × CH), 8.01 (d, J = 7.4 Hz, 1 H, CH),
8.07 (d, J = 7.5 Hz, 1 H, CH), 8.08 (s, 1 H, OH), 8.12 (d, J = 8.4 Hz,
1 H, CH), 8.18 (d, J = 7.4 Hz, 1 H, CH), 8.31 (d, J = 8.5 Hz, 1 H,
CH), 8.36 (s, 1 H, CH), 8.64 (s, 1 H, CH), 11.58 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.18 (COH), 110.96 (CH),
120.22 and 121.48 (2 × C), 122.83, 127.27, 127.40, 127.82, 127.90,
128.41, 129.01, 129.19 and 129.37 (9 × CH), 134.35, 132.42,
142.70 and 148.34 (4 × C), 163.74 and 165.38 (2 × OC=N), 173.80
(C=O).
EI-MS: m/z (%) = 388 (36, [M+]), 277 (40), 231 (40), 196 (80), 164
(54), 155 (100), 139 (24), 127 (77), 104 (20), 91 (79), 77 (27), 63
(34).
1H NMR (500.1 MHz, DMSO-d6): d = 7.20 (d, J = 8.7 Hz, 1 H,
CH), 7.60–7.66 (m, 4 H, 4 × CH), 7.89–7.94 (m, 2 H, 2 × CH), 8.14
(br s, 1 H, OH), 8.21–8.28 (m, 2 H, 2 × CH), 8.35 (d, J = 8.7 Hz, 1
H, CH), 8.46 (s, 1 H, CH), 8.98 (s, 1 H, CH), 11.61 (br s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.09 (COH), 111.03 (CH),
115.89 (C), 121.53, 124.39, 126.02, 127.87, 128.33 and 128.97
(6 × CH), 129.09, 130.48 and 130.57 (3 × C), 132.07 (CH), 142.73
and 148.49 (2 × C), 163.42 and 164.73 (2 × OC=N), 173.75 (C=O).
EI-MS: m/z (%) = 438 (6, [M+]), 262 (8), 246 (78), 219 (21), 205
(100), 190 (39), 177 (53), 164 (44), 151 (17), 88 (23), 75 (17), 63
(27).
Anal. Calcd for C24H14N4O5 (438.40): C, 65.75; H, 3.22; N, 12.78.
Found: C, 65.8; H, 3.3; N, 12.7.
3-Hydroxy-5-nitro-3-[5-(2-quinolyl)-1,3,4-oxadiazol-2-yl]-1,3-
dihydro-2H-indol-2-one (4f)
Yield: 0.38 g (97%); pale brown powder; mp 291 °C.
Anal. Calcd for C20H12N4O5 (388.34): C, 61.86; H, 3.11; N, 14.43.
Found: C, 61.9; H, 3.2; N, 14.4.
IR (KBr): 3124 (NH), 3100 (OH), 1741 (C=O), 1617, 1533, 1473,
1392, 1334, 1297, 1261, 1180, 1124, 1097, 1038, 1008, 943, 903,
842, 775, 743, 669 cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 7.18 (d, J = 8.5 Hz, 1 H,
CH), 7.72 (dd, J = 7.3, 7.2 Hz, 1 H, CH), 7.87 (dd, J = 7.5, 7.3 Hz,
1 H, CH), 8.08 (d, J = 8.1 Hz, 1 H, CH), 8.16 (s, 1 H, OH), 8.20 (d,
J = 8.3 Hz, 1 H, CH), 8.27 (d, J = 8.4 Hz, 1 H, CH), 8.32 (d, J = 9.3
Hz, 1 H, CH), 8.34 (s, 1 H, CH), 8.61 (d, J = 8.4 Hz, 1 H, CH), 11.62
(s, 1 H, NH).
Acknowledgment
This research was supported by the Research Council of University
of Tehran as a research project (6102036/1/03).
References
13C NMR (125.8 MHz, DMSO-d6): d = 72.34 (COH), 111.00,
119.72, 121.51, 127.85, 125.56 and 128.23 (5 × CH), 128.45 (C),
128.58 (CH), 129.18 (C), 129.35, 130.99 and 138.17 (3 × CH),
142.56, 142.70, 147.16 and 148.37 (4 × C), 164.80 and 164.81
(2 × OC = N), 173.66 (C = O).
EI-MS: m/z (%) = 389 (24, [M+]), 333 (10), 277 (21), 197 (60), 192
(15), 164 (43), 155 (41), 140 (15), 128 (100), 114 (9), 101 (20), 90
(22), 75 (19), 63 (24).
(1) (a) Multicomponent Reactions; Zhu, J.; Bienaymé, H., Eds.;
VCH-Wiley: Weinheim, 2005. (b) Basso, A.; Banfi, L.;
Riva, R.; Guanti, G. J. Org. Chem. 2005, 70, 575.
(c) Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2005, 44,
1602. (d) Dömling, A. Chem. Rev. 2006, 106, 17.
(e) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39,
3168.
(2) Hill, J. In Comprehensive Heterocyclic Chemistry II, Vol. 4;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon: London, 1996, Chap. 6, 267–287; and references
cited therein.
Anal. Calcd for C19H11N5O5 (389.33): C, 58.62; H, 2.85; N, 17.99.
Found: C, 58.5; H, 2.9; N, 17.8.
(3) Suwiński, J.; Szczepankiewicz, W. In Comprehensive
Heterocyclic Chemistry III, Vol 5; Katritzky, A. R.;
Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K., Eds.;
Elsevier Science: Oxford, 2008, Chap. 6, 396–458; and
references cited therein.
(4) Schinzel, E.; Martini, T.; Spatzier, W.; Probst, H. German
Patent DE 3126464, 1983; Chem. Abstr. 1983, 98, 199850.
(5) Chudgar, N. K.; Shah, S. N.; Vora, R. A. Mol. Cryst. Liq.
Cryst. 1989, 172, 51.
(6) Lozinskaya, E. I.; Shaplov, A. S.; Kotseruba, M. V.;
Komarova, L. I.; Lyssenko, K. A.; Antipin, M. Y.;
Golovanov, D. G.; Vygodskii, Y. S. J. Polym. Sci., Part A:
Polym. Chem. 2006, 44, 380.
3-Hydroxy-5-nitro-3-{5-[(E)-2-phenyl-1-ethenyl]-1,3,4-oxadia-
zol-2-yl}-1,3-dihydro-2H-indol-2-one (4g)
Yield: 0.33 g (92%); pale brown powder; mp 264–265 °C.
IR (KBr): 3186 (NH), 3106 (OH), 1758 (C=O), 1617, 1524, 1472,
1337, 1299, 1247, 1181, 1104, 1020, 961, 909, 834, 760, 719, 679
cm–1.
1H NMR (500.1 MHz, DMSO-d6): d = 7.15 (d, J = 8.9 Hz, 1 H,
CH), 7.37 (d, J = 16.6 Hz, 1 H, CH), 7.41–7.45 (m, 3 H, 3 × CH),
7.65 (d, J = 16.6 Hz, 1 H, CH), 7.80 (d, J = 8.2 Hz, 2 H, 2 × CH),
7.96 (br s, 1 H, OH), 8.29 (d, J = 2.2 Hz, 1 H, CH), 8.29 (dd, J = 8.9,
2.2 Hz, 1 H, CH), 11.53 (s, 1 H, NH).
13C NMR (125.8 MHz, DMSO-d6): d = 72.08 (COH), 109.67,
110.89, 121.28, 127.72, 127.96 and 128.90 (6 × CH), 129.20 (C),
130.11 (CH), 134.43 (C), 139.62 (CH), 142.67 and 148.28 (2 × C),
162.90 and 165.12 (2 × OC=N), 173.71 (C=O).
EI-MS: m/z (%) = 364 (21, [M+]), 289 (34), 277 (16), 262 (12), 254
(16), 172 (65), 164 (43), 159 (9), 131 (100), 117 (14), 104 (67), 91
(89), 77 (45), 57 (39).
(7) Zhang, H.; Huo, C.; Zhang, J.; Zhang, P.; Tian, W.; Wang,
Y. Chem. Commun. 2006, 281.
(8) Ikeda, T.; Mamiya, J.; Yu, Y. Angew. Chem. Int. Ed. 2007,
46, 506.
(9) Liou, G. S.; Huang, N. K.; Yang, Y. L. Eur. Polym. J. 2006,
42, 2283.
(10) Liou, G. S.; Hsiao, S. H.; Chen, W. C.; Yen, H.-J.
Macromolecules 2006, 39, 6036.
Synthesis 2010, No. 23, 4082–4086 © Thieme Stuttgart · New York

4086
M. Adib et al.
PAPER
(19) Souldozi, A.; Ramazani, A.; Bouslimani, N.; Welter, R.
Tetrahedron Lett. 2007, 48, 2617.
(20) Souldozi, A.; Ramazani, A. Tetrahedron Lett. 2007, 48,
1549.
(21) Zarudnitskii, E. V.; Pervak, I. I.; Merkulov, A. S.;
Yurchenko, A. A.; Tolmachev, A. A. Tetrahedron 2008, 64,
10431.
(22) (a) Adib, M.; Ansari, S.; Mohammadi, A.; Bijanzadeh, H. R.
Tetrahedron Lett. 2010, 51, 30. (b) Adib, M.; Ansari, S.;
Feizi, S.; Asgarian Damavandi, J.; Mirzaei, P. Synlett 2009,
3263. (c) Adib, M.; Mahdavi, M.; Ansari, S.; Malihi, F.;
Zhu, L. G.; Bijanzadeh, H. R. Tetrahedron Lett. 2009, 50,
7246. (d) Adib, M.; Sheibani, E.; Bijanzadeh, H. R.; Zhu, L.
G. Tetrahedron 2008, 64, 10681. (e) Adib, M.; Sayahi, M.
H.; Ziyadi, H.; Zhu, L. G.; Bijanzadeh, H. R. Synthesis 2008,
3289. (f) Adib, M.; Mohammadi, B.; Bijanzadeh, H. R.
Synlett 2008, 3180. (g) Adib, M.; Mohammadi, B.;
Bijanzadeh, H. R. Synlett 2008, 177.
(11) d’Ischia, M.; Napolitano, A.; Pezzella, A. In Comprehensive
Heterocyclic Chemistry III, Vol. 3; Katritzky, A. R.;
Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K., Eds.;
Elsevier Science: Oxford, 2008, Chap. 4, 353–386; and
references cited therein.
(12) Seefeld, M. A.; Miller, W. H.; Newlander, K. A.; Burgess,
W. J.; DeWolf, W. E. Jr.; Elkins, P. A.; Head, M. S.; Jakas,
D. R.; Janson, C. A.; Keller, P. M.; Manley, P. J.; Moore, T.
D.; Payne, D. J.; Pearson, S.; Polizzi, B. J.; Qiu, X.;
Rittenhouse, S. F.; Uzinskas, I. N.; Wallis, N. G.; Huffman,
W. F. J. Med. Chem. 2003, 46, 1627.
(13) Lin, N. H.; Xia, P.; Kovar, P.; Park, C.; Chen, Z.; Zhang, H.;
Rosenberg, S. H.; Sham, H. L. Bioorg. Med. Chem. Lett.
2006, 16, 421.
(14) Sechi, M.; Derudas, M.; Dallocchio, R.; Dessi, A.; Bacchi,
A.; Sannia, L.; Carta, F.; Palomba, M.; Ragab, O.; Chan, C.;
Shoemaker, R.; Sei, S.; Dayam, R.; Neamati, N. J. Med.
Chem. 2004, 47, 5298.
(15) Dassonville, A.; Breteche, A.; Evano, J.; Duflos, M.;
le Baut, G.; Grimaud, N.; Petit, J. Y. Bioorg. Med. Chem.
Lett. 2004, 14, 5441.
(16) Polshettiwar, V.; Varma, R. S. Tetrahedron Lett. 2008, 49,
879.
(23) (a) Adib, M.; Riazati Kesheh, M.; Ansari, S.; Bijanzadeh, H.
R. Synlett 2009, 1575. (b) Adib, M.; Ansari, S.; Feizi, S.;
Bijanzadeh, H. R. Synlett 2010, 921. (c) Adib, M.; Ansari,
S.; Fatemi, S.; Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron
2010, 66, 2723.
(17) Stolzenberg, H.; Weinberger, B.; Fehlhammer, W. P.;
Pühlhofer, F. G.; Weiss, R. Eur. J. Inorg. Chem. 2005, 21,
4263.
(18) Chiu, T. W.; Liu, Y. H.; Chi, K. M.; Wen, Y. S.; Lu, K. L.
Inorg. Chem. 2005, 44, 6425.
(24) Ugi, I. Isonitrile Chemistry; Academic Press: London, 1971.
(25) Ugi, I. Angew. Chem., Int. Ed. Engl. 1982, 21, 810.
(26) Walborsky, H. M.; Periasamy, M. P. In The Chemistry of
Functional Groups, Supplement C; Patai, S.; Rappaport, Z.,
Eds.; Wiley: New York, 1983, Chap. 20, 835–837.
Synthesis 2010, No. 23, 4082–4086 © Thieme Stuttgart · New York