Four-component synthesis of disubstituted 1,3,4-oxadiazole derivatives from cinnamaldehyde, an aromatic carboxylic acid, a secondary amine, and N-isocyaniminotriphenylphosphorane

Article abstract of DOI:10.1002/hc.21013

The iminium intermediate generated by the reaction between a secondary amine and cinnamaldehyde was reacted with N-isocyanimino-triphenylphosphorane in the presence of benzoic acid derivatives to form the corresponding iminophosphorane intermediate, whose intramolecular aza-Wittig reaction led to disubstituted 1,3,4-oxadiazole derivatives. The syntheses were completed under neutral conditions at room temperature to give excellent yields.

Full text of DOI:10.1002/hc.21013

Heteroatom Chemistry
Volume 00, Number 0, 2012
Four-Component Synthesis of Disubstituted
1,3,4-Oxadiazole Derivatives from
Cinnamaldehyde, an Aromatic Carboxylic Acid,
a Secondary Amine, and
N-Isocyaniminotriphenylphosphorane
Ali Ramazani,1 Robabe Kalhor,1 Aram Rezaei,2 and Zahra Karimi1
1Chemistry Department, Zanjan University, Zanjan, Iran
2Young Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Received 21 April 2011; revised 23 October 2011, 13 January 2012
biological activities such as antimicrobial, antifun-
ABSTRACT: The iminium intermediate generated
gal, antimalarial, analgesic, hypoglycemic, and an-
by the reaction between a secondary amine and
tihypertensive anti-Inflammatory [1–5]. The multi-
cinnamaldehyde was reacted with N-isocyanimino-
component condensation reactions give advantages
triphenylphosphorane in the presence of benzoic acid
to other reactions. In recent years, several tech-
derivatives to form the corresponding iminophospho-
niques have been reported for the preparation of
rane intermediate, whose intramolecular aza-Wittig
CNNPPh3 4 [6,7]. There are various methods for the
reaction led to disubstituted 1,3,4-oxadiazole deriva-
use of 4 in the synthesis of metal complexes. How-
tives. The syntheses were completed under neutral con-
ever, the application of 4 in the synthesis of organic
ditions at room temperature to give excellent yields.
compounds is uncommon. Today, most isocyanide-
ꢀ
C
2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–7,
based multicomponent reactions (IMCRs) chemistry
2012; View this article online at wileyonlinelibrary.com.
relates to the traditional reactions of Passerini and
DOI 10.1002/hc.21013
Ugi. Indeed, the wide number of various scaffolds
now available mainly builds on these two IMCRs
and their combination with other kinds of reactions
[8–31]. In recent years, the intramolecular version of
the aza-Wittig type reaction has attracted much at-
INTRODUCTION
tention because of its high potential for the synthesis
of a wide variety of nitrogen hetrocycles [32]. Lately,
we have established a one-pot technique to syn-
thesize organophosphorus compounds [32–41]. Not
many reliable simple examples have been reported
for the single-step synthesis of 1,3,4-oxadiazoles, es-
pecially from easily available carboxylic acids and
acid hydrazides [42]. In this paper, we report an effi-
cient synthetic method for the preparation of disub-
stituted 1,3,4-oxadiazole derivatives using CNNPPh3
4 chemistry [27] (Scheme 1).
1,3,4-Oxadiadoles have attracted interest in medici-
nal chemistry as surrogates of carboxylic acid. They
are an important class of heterocyclic compounds
that have a wide range of pharmaceutical and
Correspondence to: Ali Ramazani; e-mail: aliramazani@
gmail.com.
c
ꢀ
2012 Wiley Periodicals, Inc.
1

2
Ramazani et al.
5a: R= Bn, X= 4-Br; 5b: R= Et, X= 4-Br; 5c: R= Me, X= 4-Br; 5d: R= Bn, X= 3-Cl; 5e: R= Et, X= 3-Cl;
5f: R= Me, X= 3-Cl; 5g: R= Bn, X= 4-Cl; 5h: R= Et, X= 4-Cl; 5i: R= Me, X= 4-Cl; 5j: R= Bn, X= 4-F; 5k:
R= Et, X= 4-F; 5l: R= Me, X= 4-F; 5m: R= Et, X= 4-I; 5n: R= Me, X= 4-I; 5o: R= Bn, X= H.
SCHEME 1 Four-component synthesis of disubstituted 1,3,4-oxadiazole derivatives 5a–o.
RESULTS AND DISCUSSION
The structures of the products were deduced
1
from their H NMR, 13C NMR, mass, and IR spec-
As part of our ongoing program to develop highly
efficient and powerful methods for the prepara-
tion of heterocyclic compounds [43], we wish to
illustrate preparation of 1,3,4-oxadiazole deriva-
tives using four-component and one-pot reactions
of cinnamaldehyde, an aromatic carboxylic acid,
a secondary amine, and N-isocyaniminotriphen-
ylphosphorane (Scheme 1). The iminium interme-
diate formed by the reaction between a secondary
amine 2 and cinnamaldehyde 1 is trapped by N-
isocyniminotriphenylphosphorane 4 in the presence
of benzoic acid derivatives 3 to lead to the forma-
tion of disubstituted 1,3,4-oxadiazole derivatives 5
and triphenylphosphine oxide 6 (Scheme 1). The re-
action proceeds cleanly under mild conditions and
without the formation of by-products to give excel-
lent yields.
1
tra. For example, the H NMR spectrum of 5a con-
sisted of an AB-quartet for CH2 of the benzyl group at
δ = 3.72 and 3.89 ppm (2 JHH = 12.5 Hz), a doublet
3
for CH (δ = 4.9 ppm, JHH = 5 Hz), and a multiplet
at δ = 6.54–7.96 ppm for H-aromatic and H-vinylic.
The aryl groups demonstrated characteristic signals
in the aromatic region of the spectrum. 13C NMR
spectrum of 5a showed 18 separate resonances. Par-
tial assignment of these resonances is given in the
1
Experimental section. The H and 13C NMR spec-
tra of compounds 5b–o were similar to those of 5a,
except for the aromatic and aliphatic parts, which
showed characteristic signals with proper chemi-
cal shifts. The mechanism postulated for this re-
action is provided in Scheme 2. It is conceivable
that the first event is the condensation reaction
of the cinnamaldehyde 1, secondary amine 2, and
Heteroatom Chemistry DOI 10.1002/hc

Four-Component Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives
3
X
O
R
COOH
O
N
− H2O
+
H
NH
X
CHO
R
C
N
N
P(Ph)3
4
1
7
3
O
O
R
N
R
C
N
N
X
O
X
O
N
N
N
P(Ph)3
P(Ph)3
8
9
R
P(Ph)3
R
N
N
N
N
N
N
X
O
O
(Ph)3 PO
O
6
5
X
10
SCHEME 2 Proposed mechanism for the formation of disubstituted 1,3,4-oxadiazole derivatives 5a–o.
benzoic acid derivative 3 that directs to an interme-
diate iminium ion 7. The nucleophilic addition of
the (N-isocyanimino)triphenylphosphorane 4 to the
intermediate iminium ion 7 leads to a nitrilium in-
termediate 8. This intermediate may be attacked by
the conjugate base of the acid 3 to generate 1:1:1
adduct 9. This adduct may undergo an intramolec-
ular aza-Wittig reaction of an iminophosphorane
moiety with the ester carbonyl group to provide the
isolated disubstituted 1,3,4-oxadiazole 5 by the re-
moval of triphenylphosphine oxide 6.
EXPERIMENTAL
Starting materials and solvents were obtained from
Merck (Germany) and Fluka (Switzerland) and were
used without further purification. The methods used
to follow the reactions are TLC and NMR, which in-
dicated that there is no side product. IR spectra were
1
measured on a Jasco 6300 FTIR spectrometer. H
and 13C NMR spectra were measured (CDCl3) with a
Bruker DRX-250 Avance spectrometer at 250.0 and
62.09 MHz, respectively. Elemental analyses were
performed using a Heraeus CHN-O-Rapid analyzer.
Mass spectra were recorded on a Finnigan-MAT
8430 mass spectrometer operating at an ionization
potential of 20 eV. Flash chromatography columns
were prepared with Merck silica gel powder.
CONCLUSIONS
The reported method offers a mild, simple way to
prepare disubstituted 1,3,4-oxadiazole derivatives by
a multicomponent reaction including an aza-Wittig
closure. Because of the easy accessibility of the syn-
thetic approach and the neutral conditions for the
cyclization, this synthetic method has the potential
to provide various disubstituted 1,3,4-oxadiazoles,
which have a wide range of pharmaceutical and bi-
ological activities.
General Procedure
To a magnetically stirred solution of secondary
amine 2 (1.0 mmol), cinnamaldehyde 1 (1.0 mmol),
and
(N-isocyanimino)triphenylphosphorane
4
(1.0 mmol) in CH2Cl2 (5.0 mL), a solution of benzoic
Heteroatom Chemistry DOI 10.1002/hc

4
Ramazani et al.
126.74, 127.35, 128.43, 128.68, 128.75, 128.88,
129.10, 132.41 (14CH arom); 164.47, 165.61 (2C of
oxadiazole). Anal. calcd for C25H22BrN3O (460.37):
C, 65.22; H, 4.82; N, 9.13; Found: C, 65.20; H, 4.81;
N, 9.13.
acid derivative 3 (1.0 mmol) in CH2Cl2 (5.0 mL) was
added dropwise at room temperature over 15 min.
The mixture was stirred for 2 h. The solvent was
removed under reduced pressure, and the viscous
residue was purified by flash column chromatog-
raphy (silica gel powder; petroleum ether–ethyl
acetate (10:2)) to afford products 5a–o as oils. The
characterization data of the compounds are given
below.
Dibenzyl-{1-[5-(3-chloro phenyl)-[1,3,4]oxadia-
zol-2-yl]-3-phenyl allyl} Amine (5d). Yellow oil,
yield: 82%. IR (neat, cm−1): 3477, 3065, 2972, 2936,
1554, 1495, 1266, 1073, 970, 748. 1H NMR: δ =
2
3.73, 3.9 (AB quartet, 4 H, JHH = 15 Hz, 2CH2
Dibenzyl-{1-[5-(4-bromo-phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl-allyl} Amine (5a). Yellow oil, yield:
83%. IR (neat, cm−1): 3477, 3030, 2938, 1604, 1567,
3
of the benzyl group); 4.9 (d, 1H, JHH = 7.5 Hz,
CH); 6.54–8.05 (m, 21H, arom and vinylic). 13C
NMR: δ = 54.66 (CH2 of the benzyl group); 57.50
(CH); 123.23 (Cipso(C=C) of C6H4Cl); 127.31, 138.79
(2CH vinylic); 125.07, 125.51, 126.76, 128.29, 128.49,
128.71, 128.82, 130.48, 131.82 (19CH arom); 135.21,
135.45, 136.01 (3 Cipso(C=C) of 3C6H5 and CAr-Cl of
C6H4Cl); 164.05, 165.81 (2C of oxadiazole). Anal.
calcd for C31H26ClN3O (492.01): C, 75.68; H, 5.33;
N, 8.54; Found: C, 75.66; H, 5.35; N, 8.57. MS (EI):
491 (M+, 2), 400 (9), 296 (22), 196 (91), 91 (100), 65
(10).
1
1482, 1454, 1127, 835, 784. H NMR: δ = 3.72, 3.89
2
(AB quartet, 4H, JHH = 12.5 Hz, 2CH2 of benzyl
group); 4.9 (d, 1H,3 JHH = 5 Hz, CH); 6.54–7.96 (m,
21H, arom and vinylic).13C NMR: δ = 54.64 (2CH2 of
the benzyl group); 57.46 (CH); 123.27, 135.41 (2CH
vinylic); 122.81 (CAr Br of C6H4Br); 136.04, 138.82
(3Cipso(C=C) of 3C6H5); 122.81 (CAr Br of C6H4Br);
126.49 (Cipso(C=C) of C6H4Br); 126.75, 127.31, 128.28,
128.39, 128.48, 128.70, 129.13, 132.45 (19CH arom);
164.41, 165.66 (2C of oxadiazole). Anal. calcd for
C31H26BrN3O (536.46): C, 69.41; H, 4.89; N, 7.83;
Found: C, 69.39; H, 4.90; N, 7.85. MS (EI): 536 (M+,
2), 444 (7), 342 (60), 196 (100), 115 (20), 91 (90), 65
(10).
Benzyl-{1-[5-(3-chloro phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-ethyl Amine (5e). Yellow oil,
yield: 85%. IR (neat, cm−1): 3473, 3493, 2973, 1554,
1
1453, 1267, 1073, 970, 889. H NMR: δ = 1.14 (t,
3H, CH3 of Et); 2.59–2.85 (m, CH2 of Et); 3.77, 3.87
Benzyl-{1-[5-(4-bromo phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-ethyl Amine (5b). Yellow oil,
yield: 84%. IR (neat, cm−1): 3443, 3034, 2972, 1604,
1548, 1474, 1406, 1071, 835, 739. 1H NMR: δ =
1.26 (t, 3H, CH3 of Et); 2.48–2.92 (m, CH2 of Et);
2
(AB quartet, 2H, JHH = 12.5 Hz, CH2 of the benzyl
group); 4.92 (d, 1H, 3 JHH = 5 Hz, CH); 6.47–8.03 (m,
16H, arom and vinylic). 13C NMR: δ = 13.06 (CH3);
44.77 (CH2 of ethyl); 54.62 (CH2 of the benzyl group);
58.48 (CH aliphatic); 124.09 (Cipso(C=C) of C6H4Cl);
135.16 (CAr-Cl of C6H4Cl); 125.08, 134.76 (2CH
vinylic); 125.16, 136.08, 139.26 (2Cipso(C=C) of 2C6H5
and CAr-Cl of C6H4Cl); 125.25, 126.71, 126.95, 127.11,
128.20, 128.38, 128.60, 128.65, 130.43, 131.77 (14CH
arom); 163.94, 166.09 (2C of oxadiazole). Anal. calcd
for C26H24ClN3O (429.94): C, 72.63; H, 5.63; N, 9.77;
Found: C, 72.61; H, 5.66; N, 9.79.
2
3.76, 3.46 (AB quartet, 2H, JHH = 12.5 Hz, CH2
of the benzyl group); 4.92 (s, 1H, CH); 6.54–7.94
(m, 16H, arom and vinylic). 13C NMR: δ = 55.87
(2CH2 of the benzyl group); 58.62 (CH); 122.92,
135.45 (2CH vinylic); 136.45, 138.31 (2Cipso(C=C) of
2C6H5); 122.30 (CAr Br of C6H4Br); 125.97 (Cipso(C=C
)
of C6H4Br), 126.35, 127.12, 128.29, 128.45, 128.53,
128.75, 129.42, 132.65 (14CH arom); 164.22, 165.34
(2C of oxadiazole). Anal. calcd for C26H24BrN3O
(474.39): C, 65.83; H, 5.10; N, 8.86; Found: C, 65.85;
H, 5.12; N, 8.83.
Benzyl-{1-[5-(3-chloro phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-methyl Amine (5f). Yellow oil;
yield: 80%. IR (neat, cm−1): 3054, 2829, 1546, 1455,
972, 911, 741. 1H NMR: δ = 2.37 (s, 3 H, CH3);
3.75 (s, 2H, CH2 of the benzyl group); 4.80 (d,
Benzyl-{1-[5-(4-bromo phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-methyl Amine (5c). Yellow oil,
yield: 81%. IR (neat, cm−1): 3058, 2859, 1604, 1407,
1482, 1011, 835, 739. 1H NMR: δ = 2.36 (s, 3H, CH3);
3.72 (s, 2H, CH2 of the benzyl group); 4.78 (s, 1H,
CH); 6.52–7.97 (m, 16H, arom and vinylic). 13C NMR:
δ = 38.88 (CH3); 58.62 (CH2 of the benzyl group);
61.69 (CH); 123.54 (1CH vinylic); 122.76 (CAr Br
of C6H4Br); 135.39, 135.93, 138.27 (2Cipso(C=C) of
2C6H5 and 1CH vinylic); 126.74 (Cipso(C=C) of C6H4Br);
3
1 H, JHH = 5 Hz, CH); 6.52–8.08 (m, 16H, arom
and vinylic). 13C NMR: δ = 38.91 (CH3), 58.65 (CH2
of the benzyl group); 61.72 (CH); 123.55 (Cipso(C=C
)
of C6H4Cl); 127.33, 135.37 (2 CH vinylic); 135.19,
135.95, 138.28 (2Cipso(C=C) of 2C6H5 and CAr-Cl of
C6H4Cl); 125.12, 125.49, 126.75, 126.99, 128.32,
128.44, 128.68, 128.86, 130.43, 131.82 (14 CH arom);
164.04, 165.76 (2C of oxadiazole). Anal. calcd for
Heteroatom Chemistry DOI 10.1002/hc

Four-Component Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives
5
1241, 1159, 845−. 1H NMR: δ = 3.72, 3.90 (AB
C25H22ClN3O (415.91): C, 72.19; H, 5.33; N, 10.10;
Found: C, 72.17; H, 5.35; N, 10.13.
2
quartet, 2H, JHH = 12.5 Hz, CH2 of the benzyl
3
group); 4.90 (d, 1H, JHH = 5 Hz, CH); 6.54–8.11
(m, 21H, arom and vinylic),13C NMR: δ = 54.62
Dibenzyl-{1-[5-(4-chloro phenyl)-[1,3,4]oxadia-
zol-2-yl]-3-phenyl allyl} Amine (5g). Yellow oil,
yield: 82%. IR (neat, cm−1): 3479, 3033, 2950, 1560,
(CH2 of the benzyl group); 57.43 (CH); 116.54 (d,
4
2 JCF = 22.05 Hz); 120.21 (d, JCF = 3.15 Hz); 129.28
1
3
1
1450, 1265, 1075, 973, 891. H NMR: δ = 3.72, 3.89
(d, JCF = 8.82 Hz); 164.04 (d, JCF = 250.75 Hz);
123.33, 135.36, 136.05, 138.81 (3 Cipso(C=C) of 3C6H5
and 2CH vinylic); 126.74, 127.29, 128.25, 128.46,
128.66, 128.71 (15CH arom); 164.29, 165.45 (2C of
oxadiazole). Anal. calcd for C31H26FN3O (475.21): C,
78.29; H, 5.51; N, 8.84; Found: C, 78.31; H, 5.53; N,
8.86. MS (EI): 476 (M+, 5), 384 (3), 312 (10), 280
(97), 196 (100), 115 (19), 91 (80), 57 (44).
2
(AB quartet, 4 H, JHH = 12.5 Hz, 2CH2 of the ben-
3
zyl group); 4.89 (d, 1 H, JHH = 5 Hz, CH); 6.53–
8.02 (m, 21H, arom and vinylic). 13C NMR: δ =
54.66 (CH2 of the benzyl group); 57.47 (CH); 122.23
(Cipso(C=C) of C6H4Cl); 123.35, 135.39 (2CH vinylic);
136.01 (CAr-Cl of C6H4Cl); 138.06, 138.73 (3Cipso(C=C
)
of 3C6H5); 126.74, 127.31, 128.24, 128.46, 128.65,
128.72, 129.11, 129.48 (19CH arom); 164.30, 165.51
(2C of oxadiazole). Anal. calcd for C31H26ClN3O
(492.01): C, 75.68; H, 5.33; N, 8.54; Found: C, 75.67;
H, 5.35; N, 8.57.
Benzyl ethyl-{1-[5-(4-fluoro phenyl)-[1,3,4]oxa-
diazol-2-yl]-3-phenyl allyl} Amine (5k). Yellow oil,
yield: 80%. IR (neat, cm−1): 3032, 2854, 1613, 1498,
1
1453, 1260, 1159, 846, 741. H NMR: δ = 1.17 (t,
Benzyl-{1-[5-(4-chloro phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-ethyl Amine (5h). Yellow oil,
yield: 82%. IR (neat, cm−1): 3455, 3035, 2927, 1609,
3H, CH3 of Et); 2.56–2.88 (m, CH2 of Et); 3.71, 3.88
2
(AB quartet, 2H, JHH = 15 Hz, CH2 of the benzyl
3
group); 4.92 (d, 1H, JHH = 7.5 Hz, CH); 6.47–8.04
1
1482, 1445, 1093, 836. H NMR: δ = 1.25 (t, 3H,
(m, 16H, arom and vinylic). 13C NMR: δ = 13.08
CH3 of Et); 2.64–2.82 (m, CH2 of Et); 3.71, 3.87 (AB
(CH3); 44.72 (CH2 of Et); 54.60 (CH2 of the ben-
quartet, 2H, 2 JHH = 15 Hz, CH2 of the benzyl group);
2
zyl group); 58.41 (CH); 116.38 (d, JCF = 22.05 Hz);
3
4.92 (d, 1H, JHH = 5 Hz, CH); 6.47–8.21 (m, 16H,
120.25 (d, 4 JCF = 3.78 Hz); 129.26 (d, 3 JCF = 8.82 Hz);
arom and vinylic). 13C NMR: δ = 13.45 (CH3); 44.91
(CH2 of ethyl); 54.85 (CH2 of the benzyl group); 58.79
(CH aliphatic); 122.35 (Cipso(C=C) of C6H4Cl); 123.45,
135.42 (2CH vinylic); 136.32 (CAr-Cl of C6H4Cl);
138.25, 138.86 (2Cipso(C=C) of 2C6H5); 126.71, 127.33,
128.27, 128.43, 128.65, 128.72, 129.44, 129.56 (14CH
arom); 164.30, 165.51 (2C of oxadiazole). Anal. calcd
for C26H24ClN3O (429.94): C, 72.63; H, 5.63; N, 9.77;
Found: C, 72.66; H, 5.65; N, 9.74.
1
164.02 (d, JCF = 252.8 Hz); 124.25, 136.63, 136.12,
139.32 (2 Cipso(C=C) of 2C6H5 and 2CH vinylic); 126.69,
127.08, 128.16, 128.36, 128.59, 128.64 (10CH arom);
164.25, 165.74 (2C of oxadiazole). Anal. calcd for
C26H24FN3O (413.49): C, 75.52; H, 5.85; N, 10.16;
Found: C, 75.50; H, 5.88; N, 10.13.
Benzyl-{1-[5-(4-fluoro phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-methyl Amine (5l). Yellow oil,
yield: 82%. IR (neat, cm−1): 3486, 3035, 2856, 1611,
Benzyl-{1-[5-(4-chloro phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl allyl}-methyl Amine (5i). Yellow oil,
yield: 83%. IR (neat, cm−1): 3031, 2853, 2803, 1608,
1
1496, 1453, 1229, 845. H NMR: δ = 2.36 (s, 3H,
CH3); 3.72 (s, CH2 of the benzyl group); 4.79 (d,
1H, 3 JHH = 5 Hz, CH); 6.51–8.09 (m, 16H, arom and
vinylic). 13C NMR: δ = 38.75 (CH3); 58.12 (CH2 of the
1
1549, 1484, 1095, 838, 742. H NMR: δ = 2.36 (s,
3H, CH3); 3.72 (s, 2H, CH2 of the benzyl group);
2
benzyl group); 61.86 (CH); 116.50 (d, JCF = 22.08
3
4.79 (d, 1H, JHH = 7.5 Hz, CH); 6.51–8.05 (m,
4
3
Hz); 120.89 (d, JCF = 3.75 Hz); 129.26 (d, JCF
=
16H, arom and vinylic). 13C NMR: δ = 38.89 (CH3);
58.64 (CH2 of the benzyl group); 61.70 (CH); 122.34
(Cipso(C=C) of C6H4Cl); 123.58, 135.33 (2CH vinylic);
138.06, 138.30 (2Cipso(C=C) of 2C6H5); 135.96 (CAr-Cl
of C6H4Cl); 126.74, 127.32, 127.71, 128.30, 128.43,
128.68, 128.87, 129.45 (14CH arom); 165.57, 167.07
(2C of oxadiazole). Anal. calcd for C25H22ClN3O
(415.91): C, 72.19; H, 5.33; N, 10.10; Found: C, 72.16;
H, 5.36; N, 10.08.
1
8.85 Hz); 164.10 (d, JCF = 251 Hz); 124.23, 136.51,
136.45, 138.32 (2Cipso(C=C) of 2C6H5 and 2CH vinylic);
126.73, 127.10, 128.21, 128.44, 128.67, 129.39 (10CH
arom); 164.57, 165.74 (2C of oxadiazole). Anal. calcd
for C25H22FN3O (399.46): C, 75.17; H, 5.55; N, 10.52;
Found: C, 75.19; H, 5.56; N, 10.50.
Benzyl ethyl-{1-[5-(4-iodo phenyl)-[1,3,4]oxa-
diazol-2-yl]-3-phenyl allyl} Amine (5m). Yellow oil,
yield: 82%. IR (neat, cm−1): 3461, 3032, 2972, 1600,
Dibenzyl-{1-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-
2-yl]-3-phenyl-allyl}-Amine (5j). Yellow oil, yield:
82%. IR (neat, cm−1): 3033, 2857, 1612, 1455, 1498,
1
1561, 1478, 1278, 1006, 831. H NMR: δ = 1.13 (t,
3H, CH3 of Et); 2.57–2.84 (m, CH2 of Et); 3.70, 3.87
Heteroatom Chemistry DOI 10.1002/hc

6
Ramazani et al.
2
[3] Holla, B. S.; Gonsalves, R.; Shenoy, S. Eur J Med
Chem 2000, 35, 267.
(AB quartet, 2H, JHH = 15 Hz, CH2 of the benzyl
group); 4.91 (d, 1H, 3 JHH = 5 Hz, CH); 6.46–7.88 (m,
16H, arom and vinylic). 13C NMR: δ = 13.07(CH3);
44.73 (CH2 of Et); 54.60 (CH2 of the benzyl group);
[4] Crimmin, M. J.; Halon, P. J.; Rogers, N. H.; Walker,
G. J Chem Soc, Perkin Trans1 1989, 2047.
[5] Laddi, U. V.; Desai, S. R.; Bennur, R. S.; Bennur, S.
C. Ind J Hetrocycl Chem 2002, 11, 319.
[6] Stolzenberg, H.; Weinberger, B.; Fehlhammer, W. P.;
Pu¨hlhofer, F. G.; Weiss, R. Eur J Inorg Chem 2005,
21, 4263.
[7] Chiu, T. W.; Liu, Y. H.; Chi, K. M.; Wen, Y. S.; Lu, K.
L. Inorg Chem 2005, 44, 6425.
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1549.
58.45 (CH); 98.59 (CAr-I of C6H4I); 123.33 (Cipso(C=C
)
of C6H4I), 126.69, 138.32 (2CH vinylic); 136.09,
139.27 (2Cipso(C=C) of 2C6H5); 124.13, 127.09, 128.18,
128.35, 128.58, 128.64, 134.70 (14CH arom); 164.50,
165.94 (2C of oxadiazole). Anal. calcd for C26H24IN3O
(521.39): C, 59.89; H, 4.64; N, 8.06; Found: C, 59.87;
H, 4.63; N, 8.04.
[9] (a) Aller, E.; Molina, P.; Lorenzo, A. Synlett 2000, 4,
526–528; (b) Sapi, J; Laronze, J. Y. ARKIVOC 2004,
(vii), 208.
Benzyl-{1-[5-(4-iodo phenyl)-[1,3,4]oxadiazol-2-
yl]-3-phenyl allyl}-methyl Amine (5n). Yellow oil,
yield: 82%. IR (neat, cm−1): 3452, 2926, 2854, 1656,
[10] Zhu, J.; Bienayme’, H., Multicomponent Reactions;
Wiley-VCH: Weinheim, Germany, 2005.
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S. M.; Ziyaadini, M.; Marandi, G.; Khandan-Barani,
K.; Bijanzadeh, H. R. ARKIVOC 2007, (viii), 34.
[13] Do¨mling, A.; Beck, B.; Herdtweck, E.; Antuch, W.;
Oefner, C.; Yehia, N.; Gracia-Marques, A. ARKIVOC
2007, (vxii), 99.
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3168.
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8, 53; (b) Ugi, I. Pure Appl Chem 2001, 73, 187.
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[17] Banfi, L.; Guanti, G.; Riva, R.; Basso, A.; Calcagno, E.
Tetrahedron Lett 2002, 43, 4067.
[18] Neo, A. G.; Delgado, J.; Polo, C.; Marcaccini, S.; Mar-
cos, C. F. Tetrahedron Lett 2005, 46, 7977.
[19] Banfi, L.; Guanti, G.; Riva, R. Chem Commun 2000,
985.
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Chem, 1959, 71, 386.
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1
1562, 1509, 1458, 1071, 966. H NMR: δ = 2.24 (s,
2
3H, CH3); 3.75, 3.92 (AB quartet, 2H, JHH = 15 Hz,
CH2 of the benzyl group); 4.79 (d, 1 H, 3 JHH = 7.5 Hz,
CH); 6.52–7.78 (m, 16H, arom and vinylic). 13C NMR:
δ = 38.92 (CH3); 58.63 (CH2 of the benzyl group);
61.72 (CH); 98.73 (CAr-I of C6H4I); 123.28 (Cipso(C=C) of
C6H4I), 126.75, 138.35 (2CH vinylic); 135.36, 135.94
(2 Cipso(C=C) of 2C6H5); 123.54, 127.18, 127.35, 128.10,
128.37, 128.69, 128.88, 128.98 (14CH arom); 164.75,
165.62 (2C of oxadiazole). Anal. calcd for C25H22IN3O
(507.37): C, 59.18; H, 4.37; N, 8.28; Found: C, 59.21;
H, 4.35; N, 8.25.
Dibenzyl-[3-phenyl-1-(5-phenyl-[1,3,4]oxadiazol-
2-yl)-allyl] Amine (5o). Yellow oil, yield: 84%. IR
(neat, cm−1): 3027, 2939, 1558, 1494, 1452, 1072,
970, 742−. H NMR: δ = 3.72, 3.92 (AB quartet, 4H,
1
2 JHH = 12.5 Hz, 2CH2 of the benzyl group); 4.92
3
(d, 1H, JHH = 5 Hz, CH); 6.56–8.12 (m, 22H, arom
and vinylic).13C NMR: δ = 54.59 (CH2 of the benzyl
group); 57.32 (CH); 123.53, 135.24 (2CH vinylic);
132.91, 136.11, 138.88 (4Cipso(C=C) of 4C6H5); 126.75,
126.99, 127.29, 128.23, 128.48, 128.66, 128.75,
129.12, 131.81 (20CH arom); 165.12, 165.38 (2C of
oxadiazole). Anal. calcd for C31H27N3O (457.57): C,
81.37; H, 5.95; N, 9.18; Found: C, 81.36; H, 5.93; N,
9.20.
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ACKNOWLEDGMENT
This work was supported by Zanjan University.
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