The reaction of N-isocyaniminotriphenylphosphorane with 2-oxopropylbenzoate (or 4-bromobenzoate) and a primary amine in the presence of (E)-cinnamic acid derivatives: A one-pot efficient four-component reaction for the synthesis of 2-(arylamino)-2-(5-aryl-1-ethenyl-1,3,4-oxadiazol-2-yl) propyl benzoate (or 4-bromobenzoate) derivatives

Article abstract of DOI:10.1002/jhet.1563

Reactions of N-isocyaniminotriphenylphosphorane with 2-oxopropylbenzoate (or 2-oxopropyl 4-bromobenzoate) in the presence of (E)-cinnamic acids and primary amines proceed smoothly at room temperature and in neutral conditions to afford sterically congested 1,3,4-oxadiazole derivatives in high yields. The reaction proceeds smoothly and cleanly under mild conditions and no side reactions were observed.

Full text of DOI:10.1002/jhet.1563

1294
The Reaction of N-Isocyaniminotriphenylphosphorane with
2-Oxopropylbenzoate (or 4-Bromobenzoate) and a Primary Amine in the
Presence of (E)-Cinnamic Acid Derivatives: A One-Pot Efficient
Four-Component Reaction for the Synthesis of
Vol 50
2-(Arylamino)-2-(5-aryl-1-ethenyl-1,3,4-oxadiazol-2-yl)
Propyl Benzoate (or 4-Bromobenzoate) Derivatives
a
a
a
b
*
Ali Ramazani, Yavar Ahmadi, Fatemeh Zeinali Nasrabadi, and Morteza Rouhani
aChemistry Department, Zanjan University, P.O. Box 45195-313, Zanjan, Iran
bYoung Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran
*
E-mail: aliramazani@gmail.com
Received July 4, 2011
DOI 10.1002/jhet.1563
Published online 6 September 2013 in Wiley Online Library (wileyonlinelibrary.com).
R1
R2
O
C
HO
O
N
O
N
O
Ar
N
N
CH2Cl2
O
H3C
+
R1
O
+
+
R3
R2
+
(Ph)3PO
R3
O
N
H
P(Ph)3
Ar
CH3
NH2
Reactions of N-isocyaniminotriphenylphosphorane with 2-oxopropylbenzoate (or 2-oxopropyl 4-bromobenzoate)
in the presence of (E)-cinnamic acids and primary amines proceed smoothly at room temperature and in neutral
conditions to afford sterically congested 1,3,4-oxadiazole derivatives in high yields. The reaction proceeds
smoothly and cleanly under mild conditions and no side reactions were observed.
J. Heterocyclic Chem., 50, 1294 (2013).
INTRODUCTION
synthesis and library production is MCR chemistry, in which
three or more starting materials are brought together in a
highly convergent approach to rapidly build up molecular
structure and complexity [4].
1,3,4-Oxadiazoles have attracted interest in medicinal
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 antimicrobial, antifungal,
anti-inflammatory, and antihypertensive [5–9].
Several methods have been reported in the literature for
the synthesis of 1,3,4-oxadiazoles. These protocols are
multistep in nature [10–15]. The most general method
involves the cyclization of diacylhydrazides with a
variety of reagents, such as thionyl chloride, phosphorus
oxychloride, or sulfuric acid, usually under harsh reaction
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 [16–21].
In recent years, several synthetic methods have been reported
for the preparation of N-isocyaniminotriphenylphosphorane
(CNNPPh3) 6 [12,13]. There are several reports on the
use of N-isocyaniminotriphenylphosphorane (CNNPPh3) 6
in the synthesis of metal complexes [12,13]. However,
application of 6 in the synthesis of organic compounds is
Multicomponent reaction (MCR) is a chemical reaction
where three or more compounds react to form a single
product. By definition, MCRs are those reactions whereby
more than two reactants combine in a sequential manner to
give highly selective products that retain majority of the
atoms of the starting material. The development of novel
MCRs is receiving growing interest from industrial
chemistry research groups and represents a challenge for
organic chemists [1,2]. The drive toward the ideal synthesis
embracing step count, ideally just one, and yield, ideally
100%, has been pursued aggressively since scientists began
to construct molecules. Of course, there are many other
factors that affect these two aspects of synthesis, including
cost; starting material availability; safety; environmental
concerns; and overall ease of the process, including work
up and purification [3]. The nature of the synthesis project
also plays a role. Complex molecule total synthesis is often
driven by step count while showcasing innovative chemistry.
Traditional structure–activity relationship evaluations in
medicinal chemistry typically involve the preparation of an
advanced intermediate that can be analogued readily to
introduce the molecular diversity necessary to prepare a
collection, or library, of structurally related compounds.
One strategy that potentially meets the goals of total
© 2013 HeteroCorporation

November 2013
A Four-Component Reaction for the Synthesis of 2-(Arylamino)-2-
1295
(5-aryl-1-ethenyl-1,3,4-oxadiazol-2-yl) Propyl Benzoate (or 4-Bromobenzoate) Derivatives
fairly rare [22–31]. In recent years, we have established a RESULTS AND DISCUSSION
one-pot method for the synthesis of organophosphorus com-
pounds [14–22]. As part of our ongoing program to develop
efficient and robust methods for the preparation of heterocy-
clic compounds [23–35], we wish to report the synthesis of a
disubstituted 1,3,4-oxadiazole derivatives 7 by a four-
component condensation of N-isocyaniminotriphenylpho-
sphorane 6 with 2-oxopropylbenzoate (or 2-oxopropyl
4-bromobenzoate) in the presence of (E)-cinnamic acids
and primary amines (Scheme 1).
The imine intermediate generated by the reaction of primary
amine 5 with 2-oxopropyl benzoate (or 4-bromobenzoate) 3
is trapped by the N-isocyaniminotriphenylphosphorane in
the presence of an (E)-cinnamic acid derivative 4 to lead to
the formation of disubstituted 1,3,4-oxadiazole derivatives
7 and triphenylphosphine oxide (8, Scheme 1). The reaction
proceeds smoothly and cleanly under mild conditions and no
side reactions were observed.
Scheme 1. Synthesis of 2-oxopropylbenzoate (or 4-bromobenzoate) 3 and four-component synthesis of disubstituted 1,3,4-oxadiazole derivatives 7a–l
(Experimental section).
O
O
O
DMF, 100 0C, 21 h
+
CH3
R1
ONa
H3C
CH2Cl
R1
O
2
1
O
3
R2
N
C
N
N
O
Ar
OH
O
H3C
Ar
+
CH2Cl2
r. t., 6 h
3
+
+
O
+
R1
O
R3
R3
N
Ph3PO
4
N
H
(Ph)3P
8
NH2
6
5
7
R2
7a: R1=Ph, R2=Me, R3=H, Ar=C6H4; 7b: R1=Ph, R2=Me, R3=Me, Ar= C6H4; 7c: R1=4-
BrC6H4, R2=H, R3=Me, Ar= C6H4; 7d: R1=Ph, R2=H, R3=H, Ar= C6H4; 7e: R1=Ph, R2=H,
R3=Me, Ar= C6H4; 7f: R1=4-BrC6H4, R2=Me, R3=Me, Ar= C6H4; 7g: R1=Ph, R2=H, R3=H,
Ar= 4-ClC6H4; 7h: R1=4-BrC6H4, R2=H, R3=H, Ar= C6H4; 7i: R1=Ph, R2=OMe, R3=Me,
Ar= C6H4; 7j: R1=Ph, R2=H, R3=H, Ar= 4-MeC6H4; 7k: R1=Ph, R2=Me, R3=H, Ar= 3-
ClC6H4; 7l: R1=4-BrC6H4, R2=Me, R3=H, Ar= C6H4
Scheme 2. Proposed mechanism for the formation of disubstituted 1,3,4-oxadiazole derivatives 7a–l.
R2
R2
O
O
Ar
H
C
O
N
R3
H
H3C
- H2O
Ar
3
4
O
+
+
5
N
R3
O
N
O
O
CH3
O
N
C
N
N
P(Ph)3
R1
R1
P(Ph)3
10
9
6
R2
R2
P(Ph)3
O
H
N
R3
8
7
+
H
N
N
N
N
Ar
O
O
O
N
O
CH3
O
H3C
11
O
O
R3
12
R1
R1
Ar
P(Ph)3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1296
A. Ramazani, Y. Ahmadi, F. Z. Nasrabadi, and M. Rouhani
Vol 50
Heraeus CHN-O-Rapid analyzer. Mass spectra were recorded on
a FINNIGAN-MAT 8430 mass spectrometer operating at an
ionization potential of 70 eV. Flash chromatography columns
were prepared with Merck silica gel. 2-Oxopropyl benzoate (or
4-bromobenzoate) 3 [36] and N-isocyaniminotriphenylphosphorane
6 [12,13] were prepared based on known procedures.
The structures of the products were deduced from their
1H NMR, 13C NMR, mass and IR spectra. For example the
¹H NMR spectrum of 7a consisted of two singlet for the 2
CH3 (d = 1.81 and 2.30 ppm), a singlet for the NH
(d = 2.25), an AB quartet for CH2 benzyl group at d = 3.71
and 3.80 ppm (J = 12.1 Hz), an AB quartet for CH2 aliphatic
at d = 4.60 and 4.71 ppm (J = 11.0 Hz) and a multiplet at
d = 6.98–7.70ppm (H-aromatic and vinylic) and a doublet
at d = 8.00 ppm (d, 2H, J = 7.8 Hz, ortho protons of benzoate
group). The aryl groups exhibited characteristic signals in the
General procedure for the preparation of 7a–l.
To a
magnetically stirred solution of primary amine 5 [1 mmol; 0.107 g
(C6H5CH2NH2), 0.121g (4-MeC6H4CH2NH2), and 0.137 g
(4-MeOC6H4CH2NH2)], (2-oxopropyl benzoate and 2-oxopropyl
4-bromobenzoate) 3 [1 mmol; 0.178g (R = Ph) and 0.257 g
(R = 4-BrC6H4)], and N-isocyaniminotriphenylphosphorane 6
(1mmol, 0.302g) in CH2Cl2 (5 mL) was added dropwise a
solution of an (E)-cinnamic acid 4 [1 mmol; 0.148 g (Ar = C6H4),
0.162g (Ar = a-MeC6H4), 0.162g (Ar = 4-MeC6H4), and 0.182 g
(Ar = 4-ClC6H4)] in CH2Cl2 (5 mL) at room temperature over
15min. The mixture was stirred for 6 h. The solvent was removed
under reduced pressure, the viscous residue was purified by
flash column chromatography [silica gel; petroleum ether–ethyl
acetate (10:2)], and the products (7a–l) were obtained. The
solvent was removed under reduced pressure to give product 6.
The characterization data of the compounds are given in the
succeeding paragraphs.
1
aromatic region of the spectrum. The H-decoupled 13C
NMR spectrum of 7a showed 21 distinct resonances, and
partial assignment of these resonances is given in the
1
Experimental section. The H and 13C NMR spectra of
compounds 7b–l were similar to those of 7a, except
for the aromatic and aliphatic moieties, which exhibited
characteristic signals with appropriate chemical shifts.
A mechanistic rationalization for this reaction is provided
in Scheme 2. It is conceivable that the initial event is the
condensation reaction of the (E)-cinnamic acid derivative
4, 2-oxopropyl benzoate (or 4-bromobenzoate) 3, and
primary amine 5 that leads to an intermediate iminium ion
9. Nucleophilic addition of the N-isocyaniminotriphenylpho-
sphorane 6 to the intermediate iminium ion 9 leads to
nitrilium intermediate 10. This intermediate may be attacked
by the conjugate base of the acid 4 to form 1:1:1 adduct 11.
This adduct may undergo an intramolecular aza-Wittig
reaction of an iminophosphorane moiety with the ester
carbonyl group to afford the isolated disubstituted 1,3,4-
oxadiazole 7 by removal of triphenylphosphine oxide 8 from
intermediate 12.
2-[(4-Methylphenyl)amino]-2-{5-[(E)-2-phenyl-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl benzoate (7a). This compound
was obtained as yellow oil, the yield was 403 mg (89%), ir
(neat): 3388, 1720, 1642, 1447, 1266, 1105, 706 cmÀ1 1H
.
NMR (CDCl3): d 1.81, 2.30 (s, 6H, 2CH3), 2.25 (s, 1H, NH),
3.71, 3.80 (AB quartet, 2H, J = 12.1Hz, CH2 of benzyl group);
4.60, 4.71 (AB quartet, J = 11.0Hz, 2H, CH2 aliphatic), 6.98–7.70
(m, 14H, H-Ar and Vinylic), 8.00 (d, 2H, J = 7.8 Hz, H-Ar). 13C
NMR (CDCl3): d 21.07 (2CH3), 47.50 (CH2 of benzyl group),
56.70 (C aliphatic), 69.14 (CH2 aliphatic), 109.84 and 136.90
(2 CH, vinylic), 129.52, 133.32, 134.61, 136.65 (4C arom),
127.48, 128.13, 128.50, 129.01, 129.19, 129.68, 130.03, 139.15
(14CH arom), 164.82, 165.83 (2C of oxadiazole), 167.58 (C of
benzoate group). EI ms: m/z: 453 (M+), 390 (5), 212 (29), 190
(34), 171 (100), 149 (16), 105 (81), 77 (21), 57 (9). Anal. Calcd.
for C28H27N3O3 (453.53): C, 74.15; H, 6.00; N, 9.27. Found: C,
74.11; H, 6.03; N, 9.32.
CONCLUSIONS
The reported method offers a mild, simple, and efficient
route for the preparation of sterically congested
1,3,4-oxadiazole derivatives 7 from 2-oxopropyl benzoate
(or 4-bromobenzoate) 3, primary amine 5, N-isocyanimi-
notriphenylphosphorane 6 and (E)-cinnamic acids 4. Its
ease of work-up, high yields, and fairly mild reaction
conditions makes it a useful addition to modern synthetic
methodologies.
2-[(4-Methylbenzyl)amino]-2-{5-[(E)-1-methyl-2-phenyl-1-
ethenyl]-1,3,4-oxadiazol-2-yl}propyl benzoate (7b). This
compound was obtained as yellow oil, the yield was 406 mg
(87%), ir (neat): 3313, 2914, 1719, 1446, 1261, 1090,
1
704 cmÀ1. H NMR (CDCl3): d 1.80, 2.30, 2.38 (s, 9H, 3CH3),
2.27 (s, 1H, NH), 3.72, 3.80 (AB quartet, 2H, J = 12.1 Hz, CH2
of benzyl group); 4.59, 4.70 (AB quartet, J = 10.9 Hz, 2H, CH2
aliphatic), 6.97–7.70 (m, 13H, H-Ar and vinylic), 8.00 (d, 2H,
J = 7.8 Hz, H-Ar). 13C NMR (CDCl3): d 14.56, 21.07 (3CH3),
47.54 (CH2 of benzyl group), 56.67 (C aliphatic), 69.24 (CH2
aliphatic), 121.36 (CH, vinylic), 128.34, 134.41, 135.41,
136.70 (4C arom), 128.16, 128.48, 129.18, 129.54, 129.68,
133.28 (14CH arom), 136.86 (C, vinylic), 165.83, 166.93 (2C
of oxadiazole), 167.85 (C of benzoate group). EI ms: m/z: 467
(M+), 313 (11), 226 (19), 185 (100), 149 (13), 105 (55), 77
(19). Anal. Calcd. for C29H29N3O3 (467.56): C, 74.50; H, 6.25;
N, 8.99. Found: C, 74.53; H, 6.21; N, 9.02.
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 indicated that there is no side product.
Melting points were measured on an Electrothermal 9100
apparatus and are uncorrected. IR spectra were measured on a
2-(Benzylamino)-2-{5-[(E)-1-methyl-2-phenyl-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl 4-bromobenzoate (7c). This
compound was obtained as yellow oil, the yield was 452 mg
1
Jasco 6300 FTIR spectrometer (Tokyo, Japan). H and 13C NMR
spectra were measured (CDCl3) with a BRUKER DRX-250
AVANCE spectrometer (Billerica, MA) at 250.0 and 62.5 MHz,
respectively. Elemental analyses were performed using a
1
(85%), ir (neat): 3350, 2920, 1721, 1447, 1268, 710 cmÀ1. H
NMR (CDCl3): d 1.78, 2.38 (s, 6H, 2CH3), 2.23 (s, 1H, NH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2013
A Four-Component Reaction for the Synthesis of 2-(Arylamino)-2-
1297
(5-aryl-1-ethenyl-1,3,4-oxadiazol-2-yl) Propyl Benzoate (or 4-Bromobenzoate) Derivatives
3.75, 3.82 (AB quartet, 2H, J = 12.3 Hz, CH2 of benzyl group);
4.57, 4.70 (AB quartet, J = 11.1Hz, 2H, CH2 aliphatic), 7.27–7.70
(m, 13H, H-Ar and vinylic), 7.85 (d, 2H, J = 8.3 Hz, H-Ar). 13C
NMR (CDCl3): d 14.59, 21.05 (2CH3), 47.80 (CH2 of benzyl
group), 56.69 (C aliphatic), 69.32 (CH2 aliphatic), 121.30 (CH,
vinylic), 128.41, 134.50, 135.32, 155.26 (4C arom), 127.26,
128.18, 128.53, 129.52, 131.17, 131.88 (14CH arom), 139.68
(C, vinylic), 165.13, 167.31 (2C of oxadiazole), 167.65 (C
of benzoate group). EI ms: m/z: 533 (M+, 26), 427 (70), 347
(20), 317 (100), 277 (34), 225 (96), 185 (95), 157 (68), 106
(92), 77 (28), 42 (8). Anal. Calcd. for C28H26BrN3O3
(532.43): C, 63.16; H, 4.92; N, 7.89. Found: C, 63.21; H,
4.95; N, 7.87.
3418, 1600, 1526, 1268, 709 cmÀ1 1H NMR (CDCl3): d 1.80
.
(s, 3H, CH3), 2.23 (s, 1H, NH), 3.76, 3.83 (AB quartet, 2H,
J = 12.4 Hz, CH2 of benzyl group); 4.58, 4.71 (AB quartet,
J = 10.6 Hz, 2H, CH2 aliphatic), 6.97 (d, 1H, J = 16.5Hz,
H-vinyl); 7.18–7.70 (m, 13H, H-Ar and vinylic), 8.00 (d, 2H,
J = 8.0Hz, H-Ar). 13C NMR (CDCl3): d 21.0 (CH3), 47.71 (CH2
of benzyl group), 56.74 (C aliphatic), 69.08 (CH2 aliphatic),
110.36 and 137.77 (2CH, vinylic), 129.46, 135.91, 139.65,
155.68 (4C arom), 127.26, 128.14, 128.51, 128.62, 129.28,
129.67, 133.07, 133.35 (14CH arom), 164.60, 165.81 (2C of
oxadiazole), 167.63 (C of benzoate group). Anal. Calcd. for
C27H24ClN3O3 (473.95): C, 68.42; H, 5.10; N, 8.87. Found: C,
68.37; H, 5.14; N, 8.90.
2-(Benzylamino)-2-{5-[(E)-2-phenyl)-1-ethenyl]-1,3,4-oxadiazol-
2-yl}propyl benzoate (7d). This compound was obtained as yellow
oil, the yield was 364 mg (83%), ir (neat): 3431, 2923, 1719, 1589,
2-(Benzylamino)-2-{5-[(E)-2-phenyl-1-ethenyl]-1,3,4-oxadiazol-
2-yl}propyl 4-bromobenzoate (7h). This compound was obtained
as yellow oil, the yield was 414 mg (80%), ir (neat): 3429,
1266, 754 cmÀ1
.
1H NMR (CDCl3): d 1.81 (s, 3H, CH3), 2.26
2926, 1723, 1450, 1248, 711 cmÀ1 1H NMR (CDCl3): d 1.79
.
(s, 1H, NH), 3.76, 3.84 (AB quartet, 2H, J = 12.4Hz, CH2 of
benzyl group); 4.60, 4.73 (AB quartet, J = 11.0 Hz, 2H, CH2
aliphatic), 7.02 (d, 1H, J = 16.5Hz, H-vinyl); 7.10–7.70 (m, 14H,
H-Ar and vinylic), 8.00 (d, 2H, J = 7.8 Hz, H-Ar). 13C NMR
(CDCl3): d 21.06 (CH3), 47.76 (CH2 of benzyl group), 56.76 (C
aliphatic), 69.12 (CH2 aliphatic), 109.84 and 134.60 (2CH,
vinylic), 129.50, 133.33, 139.20 (3C arom), 127.26, 127.49,
128.18, 128.51, 129.01, 129.68, 130.04, 139.71 (15CH arom),
164.85, 165.83 (2C of oxadiazole), 167.53 (C of benzoate group).
Anal. Calcd. for C27H25N3O3 (439.51): C, 73.78; H, 5.73; N,
9.56. Found: C, 73.74; H, 5.69; N, 9.59.
(s, 3H, CH3), 2.23 (s, 1H, NH), 3.75, 3.82 (AB quartet, 2H,
J = 12.4 Hz, CH2 of benzyl group); 4.58, 4.72 (AB quartet,
J = 11.0 Hz, 2H, CH2 aliphatic), 6.99 (d, 1H, J = 16.5Hz,
H-vinyl); 7.12–7.70 (m, 13H, H-Ar and vinylic), 7.85 (d, 2H,
J = 7.9Hz, H-Ar). 13C NMR (CDCl3): d 21.03 (CH3), 47.76 (CH2
of benzyl group), 56.73 (C aliphatic), 69.22 (CH2 aliphatic),
109.75 and 139.26 (2CH, vinylic), 128.42, 134.53, 139.63,
155.25 (4C arom), 127.29, 127.48, 128.14, 128.52, 129.04,
130.08, 131.17, 131.88 (14CH arom), 164.85, 165.12 (2C of
oxadiazole), 167.38 (C of benzoate group). Anal. Calcd. for
C27H24BrN3O3 (518.40): C, 62.56; H, 4.67; N, 8.11. Found: C,
62.61; H, 4.63; N, 8.15.
2-(Benzylamino)-2-{5-[(E)-1-methyl-2-phenyl)-1-ethenyl]-1,3,
4-oxadiazol-2-yl}propyl benzoate (7e). This compound was
obtained as yellow oil, the yield was 385mg (85%), ir (neat):
2-[(4-Methoxybenzyl)amino]-2-{5-[(E)-1-methyl-2-phenyl-
1-ethenyl]-1,3,4-oxadiazol-2-yl}propyl benzoate (7i). This
compound was obtained as yellow oil, the yield was 398 mg
3383, 1718, 1448, 1265, 707 cmÀ1 1H NMR (CDCl3): d 1.80,
.
2.38 (s, 6H, 2CH3), 2.23 (s, 1H, NH), 3.77, 3.84 (AB quartet, 2H,
J = 12.4Hz, CH2 of benzyl group); 4.60, 4.71 (AB quartet,
J = 10.9Hz, 2H, CH2 aliphatic), 7.30–7.70 (m, 14H, H-Ar and
vinylic), 8.00 (d, 2H, J = 8.0 Hz, H-Ar). 13C NMR (CDCl3): d
14.58, 21.07 (2CH3), 47.79 (CH2 of benzyl group), 56.71 (C
aliphatic), 69.19 (CH2 aliphatic), 121.34 (CH, vinylic), 129.87,
134.45, 135.39 (3C arom), 127.21, 128.19, 128.35, 128.49,
129.53, 129.67, 129.87, 133.30 (15CH arom), 139.76 (C, vinylic),
165.82, 167.30 (2C of oxadiazole), 167.80 (C of benzoate group).
Anal. Calcd. for C28H27N3O3 (453.53): C, 74.15; H, 6.0; N, 9.27.
Found: C, 74.18; H, 6.05; N, 9.23.
(84%), ir (neat): 3436, 2923, 1722, 1589, 1447, 1266, 754 cmÀ1
.
1H NMR (CDCl3): d 1.79, 2.38 (s, 6H, 2CH3), 2.21 (s, 1H, NH),
3.76 (s, 3H, OCH3); 3.70, 3.80 (AB quartet, 2H, J = 12.4Hz,
CH2 of benzyl group); 4.59, 4.70 (AB quartet, J = 11.0Hz, 2H,
CH2 aliphatic), 6.80 (d, 2H, J = 7.8 Hz, H-arom); 7.10–7.70 (m,
11H, H-Ar and vinylic), 8.00 (d, 2H, J = 7.9 Hz, H-Ar). 13C
NMR (CDCl3): d 14.57, 21.08 (2CH3), 47.22 (CH2 of benzyl
group), 55.24 (OCH3), 56.64 (C aliphatic), 69.20 (CH2
aliphatic), 121.37 (CH, vinylic), 128.33, 131.83, 134.42, 158.82
(4C arom), 113.89, 128.47, 129.40, 129.53, 129.67, 133.27
(14CH arom), 135.42 (C, vinylic), 165.82, 167.28 (2C of
oxadiazole), 167.85 (C of benzoate group). Anal. Calcd. for
C29H29N3O4 (483.60): C, 72.03; H, 6.04; N, 8.69. Found: C,
71.98; H, 6.09; N, 8.64.
2-[(4-Methylbenzyl)amino]-2-{5-[(E)-1-methyl-2-phenyl-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl 4-bromobenzoate (7f). This compound
was obtained as yellow oil, the yield was 431 mg (79%), ir (neat):
3425, 2924, 1723, 1600, 1268, 756 cmÀ1
.
1H NMR (CDCl3): d
2-(Benzylamino)-2-{5-[(E)-2-(4-methylphenyl)-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl benzoate (7j). This compound was
obtained as yellow oil, the yield was 385mg (85%), ir (neat):
1.77, 2.30, 2.38 (s, 9H, 3CH3), 2.24 (s, 1H, NH), 3.70, 3.78
(AB quartet, 2H, J=12.1Hz, CH2 of benzyl group); 4.56, 4.69
(AB quartet, J= 11.1 Hz, 2H, CH2 aliphatic), 7.02–7.70 (m, 12H,
H-Ar and vinylic), 7.85 (d, 2H, J= 7.9 Hz, H-Ar). 13C NMR
(CDCl3): d 14.57, 14.69, 21.02 (3CH3), 47.54 (CH2 of benzyl
group), 56.64 (C aliphatic), 69.35 (CH2 aliphatic), 121.38 (CH,
vinylic), 128.44, 134.45, 135.04, 135.34, 155.26 (5C arom),
128.16, 128.48, 128.53, 129.19, 129.52, 131.17, 131.87 (13CH
arom), 136.61 (C, vinylic), 165.12, 167.28 (2C of oxadiazole),
167.69 (C of benzoate group). Anal. Calcd. for C29H28BrN3O3
(546.45): C, 63.74; H, 5.16; N, 7.69. Found: C, 63.70; H,
5.13; N, 7.72.
3415, 1724, 1590, 1268, 709 cmÀ1 1H NMR (CDCl3): d 1.80,
.
2.39 (s, 6H, 2CH3), 2.24 (s, 1H, NH), 3.76, 3.84 (AB quartet, 2H,
J = 12.4 Hz, CH2 of benzyl group); 4.60, 4.72 (AB quartet,
J = 10.9 Hz, 2H, CH2 aliphatic), 6.97 (d, 1H, J = 16.5Hz, H-
vinyl); 7.11–7.71 (m, 13H, H-Ar and vinylic), 8.00 (d, 2H,
J = 7.5Hz, H-Ar). 13C NMR (CDCl3): d 21.05, 21.46 (2CH3),
47.76 (CH2 of benzyl group), 56.74 (C aliphatic), 69.14 (CH2
aliphatic), 108.78 and 139.18 (2CH, vinylic), 129.52, 131.89,
139.73, 140.43 (4C arom), 127.24, 127.46, 128.18, 128.50,
129.68, 129.73, 133.31 (14CH arom), 165.02, 165.83 (2C of
oxadiazole), 167.39 (C of benzoate group). Anal. Calcd. for
C28H27N3O3 (453.53): C, 74.15; H, 6.0; N, 9.27. Found: C,
74.19; H, 6.06; N, 9.23.
2-(Benzylamino)-2-{5-[(E)-2-(4-chlorophenyl)-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl benzoate (7g).
This compound
was obtained as yellow oil, the yield was 383mg (81%), ir (neat):
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1298
A. Ramazani, Y. Ahmadi, F. Z. Nasrabadi, and M. Rouhani
Vol 50
[10] Ramazani, A.; Ahmadi, Y.; Rouhani, M.; Shajari, N.;
Souldozi, A. Heteroat Chem 2010, 21, 368.
[11] Ramazani, A.; Shajari, N.; Mahyari, A.; Ahmadi, Y. Mol
Divers 2011, 15, 521.
[12] Stolzenberg, H.; Weinberger, B.; Fehlhammer, W. P.;
Pühlhofer, F. G.; Weiss, R. Eur J Inorg Chem 2005, 21, 4263.
[13] Chiu, T. W.; Liu, Y. H.; Chi, K. M.; Wen, Y. S.; Lu, K. L.
Inorg Chem 2005, 44, 6425.
[14] Yavari, I.; Ramazani, A.; Yahya-Zadeh, A. Synth Commun
1996, 26, 4495-4499.
[15] Yavari, I.; Ramazani, A. Phosphorus, Sulfur, Silicon 1997, 130, 73.
[16] Ramazani, A.; Bodaghi, A. Tetrahedron Lett 2000, 41, 567.
[17] Pakravan, P.; Ramazani, A.; Noshiranzadeh, N.; Sedrpoushan,
A. Phosphorus, Sulfur, Silicon 2007, 182, 545.
[18] Ramazani, A.; Rahimifard, M.; Souldozi, A. Phosphorus,
Sulfur, Silicon 2007, 182, 1.
[19] Ramazani, A.; Rahimifard, M.; Noshiranzadeh, N.; Souldozi,
A. Phosphorus, Sulfur, Silicon 2007, 182, 413.
[20] Ramazani, A.; Ahmadi, E.; Kazemizadeh, A. R.; Dolatyari, L.;
Noshiranzadeh, N.; Eskandari, I.; Souldozi, A. Phosphorus, Sulphur,
Silicon 2005, 180, 2419.
[21] Ramazani, A.; Mohammadi-Vala, M. A. Phosphorus, Sulfur,
Silicon 2001, 176, 223.
[22] Ramazani, A.; Amini, I.; Massoudi, A. Phosphorus, Sulphur,
Silicon 2006, 181, 2225.
[23] Souldozi, A.; Ramazani, A.; Bouslimani, N.; Welter, R.
Tetrahedron Lett 2007, 48, 2617.
[24] Souldozi, A.; Ramazani, A. Tetrahedron Lett 2007, 48, 1549.
[25] Souldozi, A.; Ramazani, A. Phosphorus, Sulfur, Silicon 2009,
184, 3191.
2-{5-[(E)-2-(3-Chlorophenyl)-1-ethenyl]-1,3,4-oxadiazol-2-yl}-
2-[(4-methylbenzyl)amino]- propyl benzoate (7k). This
compound was obtained as yellow oil, the yield was 400 mg
1
(82%), ir (neat): 3375, 1724, 1446, 1268, 705 cmÀ1. H NMR
(CDCl3): d 1.80, 2.30 (s, 6H, 2CH3), 2.24 (s, 1H, NH), 3.70,
3.80 (AB quartet, 2H, J = 11. Hz, CH2 of benzyl group); 4.58,
4.71 (AB quartet, J = 11.0 Hz, 2H, CH2 aliphatic), 6.99 (d,
1H, J = 16.8 Hz, H-vinyl); 7.07 (d, 2H, J = 7.8 Hz, H-arom),
7.19–7.70 (m, 10H, H-Ar and vinylic), 7.99 (d, 2H, J = 7.8 Hz,
H-Ar). 13C NMR (CDCl3): d 21.02 (2CH3), 47.46 (CH2 of
benzyl group), 56.71 (C aliphatic), 69.07 (CH2 aliphatic),
111.23 and 137.52 (2CH, vinylic), 129.85, 135.04, 136.40,
136.89, 155.58 (5C arom), 125.41, 127.44, 128.08, 128.51,
129.18, 129.67, 133.34, 136.62 (13CH arom), 165.25, 165.83
(2C of oxadiazole), 167.66 (C of benzoate group). Anal. Calcd.
for C28H26ClN3O3 (488.0): C, 68.92; H, 5.37; N, 8.61. Found:
C, 68.88; H, 5.34; N, 8.66.
2-[(4-Methylphenyl)amino]-2-{5-[(E)-2-phenyl-1-ethenyl]-
1,3,4-oxadiazol-2-yl}propyl 4-bromobenzoate (7l). This
compound was obtained as yellow oil, the yield was 415 mg
(78%), ir (neat): 3428, 1721, 1447, 1268, 1109, 709 cmÀ1 1H
.
NMR (CDCl3): d 1.78, 2.29 (s, 6H, 2CH3), 2.25 (s, 1H, NH),
3.69, 3.77 (AB quartet, 2H, J = 12.1 Hz, CH2 of benzyl group);
4.56, 4.70 (AB quartet, J = 11.0Hz, 2H, CH2 aliphatic), 6.96–7.70
(m, 13H, H-Ar and vinylic), 7.88 (d, 2H, J = 7.8 Hz, H-Ar). 13C
NMR (CDCl3): d 21.05 (2CH3), 47.52 (CH2 of benzyl group),
56.78 (C aliphatic), 69.18 (CH2 aliphatic), 109.74 and 136.82
(2 CH, vinylic), 129.57, 130.15, 134.50, 135.36, 155.82 (5C
arom), 127.47, 127.57, 128.10, 129.04, 129.19, 131.17, 131.87
(13CH arom), 165.72, 167.30 (2C of oxadiazole), 167.78 (C of
benzoate group). Anal. Calcd. for C28H26BrN3O3 (532.43): C,
63.16; H, 4.92; N, 7.89. Found: C, 63.19; H, 4.96; N, 7.85.
[26] Ramazani, A.; Souldozi, A. Phosphorus, Sulfur, Silicon 2009,
184, 2350.
[27] (a) Ramazani, A.; Souldozi, A. Arkivoc 2008, xvi, 235; (b)
Ramazani, A.; Nasrabadi, F. Z.; Ahmadi, Y. Helv Chim Acta 2011, 94,
1024; (c) Ramazani, A.; Ahmadi, Y.; Nasrabadi, F. Z. Z Naturforsch
2011, 66b, 184; (d) Ramazani, A.; Ahmadi, Y.; Mahyari, A. Synthetic
Comm 2011, 41, 2273; (e) Ramazani, A.; Nasrabadi, F. Z.; Mashhadi
Malekzadeh, A.; Ahmadi, Y. Monatsh Chem 2011, 142, 625; (f)
Nasrabadi, F. Z.; Ramazani, A.; Ahmadi, Y. Mol Divers 2011, 15, 791;
(g) Shajari, N.; Ramazani, A.; Ahmadi, Y. Bull Chem Soc Ethiop 2011,
25, 1; (h) Ramazani, A.; Nasrabadi, F. Z.; Karimi, Z.; Rouhani, M. Bull
Korean Chem Soc 2011, 32, 2700; (i) Ramazani, A.; Farshadi, A.;
Mahyari, A.; Ślepokura, K.; Lis, T.; Rouhani, M. J Chem Crystallogr
2011, 41, 1376; (k) Ramazani, A.; Rouhani, M.; Rezaei, A.; Shajari, N.;
Souldozi, A. Helv Chim Acta 2011, 94, 282.
Acknowledgment. This work was supported by the Zanjan
University.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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