A one-pot efficient four-component reaction for the synthesis of 2-(arylamino)-2-(5-aryl-1,3,4-oxadiazol-2-yl)propyl benzoate (or acetate) derivatives

Article abstract of DOI:10.1002/hc.20735

Reactions of (N-isocyanimino) triphenylphosphorane with 2-oxopropylbenzoate (or acetate) in the presence of aromatic carboxylic 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/hc.20735

Heteroatom Chemistry
Volume 22, Number 6, 2011
A One-Pot Efficient Four-Component Reaction
for the Synthesis of 2-(Arylamino)-2-
(5-aryl-1,3,4-oxadiazol-2-yl)propyl Benzoate
(or Acetate) Derivatives
Ali Ramazani,1 Yavar Ahmadi,1 Asemeh Mashhadi Malekzadeh,1
and Aram Rezaei2
1Chemistry Department, Zanjan University, P. O. Box 45195-313, Zanjan, Iran
2Young Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Received 21 February 2011; revised 18 May 2011
all the organic reagents employed are consumed
ABSTRACT: Reactions of (N-isocyanimino)
and are incorporated into the target compound [1].
triphenylphosphorane with 2-oxopropylbenzoate
MCRs, leading to interesting heterocyclic scaffolds,
(or acetate) in the presence of aromatic carboxylic
are particularly useful for the construction of di-
acids and primary amines proceed smoothly at room
verse chemical libraries of “drug-like” molecules.
temperature and in neutral conditions to afford ster-
The isocyanide-based MCRs are especially impor-
ically congested 1,3,4-oxadiazole derivatives in high
tant in this area [2,3].
yields. The reaction proceeds smoothly and cleanly
Among the known MCRs to date, the most
under mild conditions, and no side reactions were
valuable reactions are those based on isocyanides.
ꢀ
C
observed.
2011 Wiley Periodicals, Inc. Heteroatom
Isocyanide-based MCRs (abbreviated to IMCRs by
Ugi and Do¨mling) by virtue of their synthetic po-
tential, inherent atom efficiency, convergent nature,
ease of implementation, and generation of molecu-
lar diversity, have attracted much attention because
of the advantages that they offer to the field of com-
binatorial chemistry [4].
During recent years, there has been consider-
able investigation on different classes of oxadia-
zoles. In particular, compounds containing a 1,3,4-
oxadiazole nucleus have been shown to possess
a wide range of pharmacological and therapeu-
tic activities. Some 1,3,4-oxadiazoles have exhibited
analgesic, antiinflammatory, anticonvulsant, tran-
quilizing, myorelaxant, antidepressant, vasodilata-
tory, diuretic, antiulcer, antiarythmic, antiserotonin,
spasmolytic, hypotensive, antibronchoconstrictive,
anticholinergic, and antiemetic activities. Further-
more, many 1,3,4-oxadiazole derivatives have been
Chem 22:692–698, 2011; View this article online at
wileyonlinelibrary.com. DOI 10.1002/hc.20735
INTRODUCTION
Multicomponent reactions (MCRs) have emerged as
an efficient and powerful tool in modern synthetic
organic chemistry due to their valued features such
as atom economy, straightforward reaction design,
and the opportunity to construct target compounds
by the introduction of several diverse elements in
a single chemical event. Typically, purification of
products resulting from MCRs is also simple since
Correspondence to: Ali Ramazani; e-mail: aliramazani@
gmail.com.
c
ꢀ
2011 Wiley Periodicals, Inc.
692

A One-Pot Efficient Four-Component Reaction for the Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives 693
TABLE
1 Synthesis of Disubstituted 1,3,4-Oxadiazole
reported as active inhibitors of several enzymes
[5,6].
Derivatives 7 (See Scheme 1)
The intramolecular version of the aza-Wittig-
type reaction has attracted considerable attention
recently because of its high potential for the syn-
thesis of a wide variety of nitrogen heterocycles,
which can be attributed, in good measure, to the
rapid progress in the preparation of functionalized
iminophosphoranes. The nucleophilicity of the ni-
trogen is a factor of essential mechanistic impor-
tance in the use of these iminophosphoranes as aza-
Wittig reagents. Iminophosphoranes are important
reagents in synthetic organic chemistry, especially
in the synthesis of naturally occurring products,
compounds with biological and pharmacologi-
cal activity [7–11]. However, the organic chem-
istry of (N-isocyanimino)triphenylphosphorane 6
remains almost unexplored. (N-Isocyanimino)
triphenylphosphorane 6 is expected to have syn-
7
R1
R2
Ar
Yield of 7 (%)a
a
b
c
d
e
f
g
h
i
Ph
Ph
Ph
H
CH3
CH3
H
H
H
CH3
F
F
H
H
3,5-diMeC6H4
3,5-diMeC6H4
3,4-diMeC6H4
3,4-diMeC6H4
3,5-diMeC6H4
4-MeC6H4
4-MeC6H4
3,5-diMeC6H4
2-BrC6H4
4-BrC6H4
4-ClC6H4
4-ClC6H4
3,5-diMeC6H4
85
87
82
86
87
88
85
84
81
86
85
83
85
Ph
CH3
CH3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
j
k
l
OCH3
OCH3
m
aYield of isolated products.
thetic potential because it provides
a
reac-
tion system in which the iminophosphorane
group can react with a reagent having carbonyl
functionality [12,13]. In this paper, we report
an interesting four-component reaction of (N-
isocyanimino)triphenylphosphorane 6 (Scheme 1).
stituted 1,3,4-oxadiazole derivatives 7 by a four-
component condensation of primary amine 5,
(N-isocyanimino)triphenylphosphorane 6, aromatic
carboxylic acid derivatives 4, and 2-oxopropyl ben-
zoate (or acetate) 3 (Scheme 1). The imine interme-
diate generated by the reaction of primary amine 5
with 2-oxopropyl benzoate (or acetate) 3 is trapped
by the (N-isocyanimino)triphenylphosphorane in
the presence of an aromatic carboxylic acid deriva-
tive 4 leading to the formation of disubstituted 1,3,4-
oxadiazole derivatives 7 and triphenylphosphine ox-
ide (8; Scheme 1 and Table 1). The reaction proceeds
smoothly and cleanly under mild conditions, and no
side reactions were observed.
RESULTS AND DISCUSSION
In recent years, we have established a one-pot
method for the synthesis of organophosphorus
compounds [14–22]. As part of our ongoing pro-
gram to develop efficient and robust methods for
the preparation of heterocyclic compounds [23–
35], we wish to report the synthesis of disub-
SCHEME 1 Synthesis of 2-oxopropylbenzoate (or acetate) 3 and four-component synthesis of disubstituted 1,3,4-oxadiazole
derivatives 7a–m (see Table 1 and the Experimental section).
Heteroatom Chemistry DOI 10.1002/hc

694 Ramazani et al.
The structures of the products were deduced
from their 1H NMR, 13C NMR, and mass and IR spec-
tra. For example, the H NMR spectrum of 7a con-
rected. IR spectra were measured on a Jasco 6300
1
FTIR spectrometer. H- and 13C NMR spectra were
1
measured (CDCl3) with a Bruker DRX-250 Avance
spectrometer at 250.0 and 62.5 MHz, respectively.
Elemental analyses were performed using a Heraeus
CHN-O-Rapid analyzer. Mass spectra were recorded
on a Finnigan-MAT 8430 mass spectrometer operat-
ing at an ionization potential of 20 eV. Flash chro-
matography columns were prepared with Merck sil-
ica gel. 2-Oxopropyl benzoate (or acetate) 3 was
prepared based on the known procedure [36].
sisted of two singlets for the 3 CH3(δ = 1.83 and 2.36
ppm), a singlet for the NH (δ = 2.08, exchangeable by
D2O), an AB-quartet for the CH2 of a benzyl group at
δ = 3.74 and 3.83 ppm (2 JHH = 12.4 Hz), an AB-
quartet for the CH2 aliphatic at δ = 4.60 and 4.73 ppm
(2 JHH = 10.9 Hz), and a multiplet at δ = 7.15–
8.01 ppm for the H-aromatic. The aryl groups ex-
hibited characteristic signals in the aromatic region
1
of the spectrum. The H decoupled 13C NMR spec-
trum of 7a showed 20 distinct resonances; partial
assignment of these resonances is given in the Ex-
General Procedure for the Preparation of 7a − m
1
perimental section. The H and 13C NMR spectra of
To a magnetically stirred solution of primary amine
5 (1 mmol; 0.107 g (C6H5CH2NH2), 0.121 g (4-
MeC6H4CH2NH2), 0.125 g (4-FC6H4CH2NH2), and
0.137 g (4-MeOC6H4CH2NH2)), an ester deriva-
tive of 2-oxopropyl alcohol 3 (2-oxopropyl ac-
etate and 2-oxopropyl benzoate) (1 mmol; 0.116
g (R = CH3) and 0.178 g (R = Ph)) and (N-
isocyanimino)triphenylphosphorane 6 (1 mmol,
0.302 g) in CH2Cl2 (5 mL) was added dropwise a solu-
tion of an aromatic carboxylic acid 4 (1 mmol; 0.150
g (Ar = 3,5-diMeC6H4), 0.150 g (Ar = 3,4-diMeC6H4),
0.136 g (Ar = 4-MeC6H4), 0.201 g (Ar = 4-BrC6H4),
and 0.157 g (Ar = 4-ClC6H4)) in CH2Cl2 (5 mL) at
room temperature for more than 15 min. The mix-
ture was stirred for 3 h. The solvent was removed
under reduced pressure, and the viscous residue was
purified by flash column chromatography (silica gel;
petroleum ether–ethyl acetate (10:1)), and the prod-
ucts (7a–m) were obtained. The physical and spec-
tral data of the compounds are given below.
compounds 7b–m were similar to those of 7a, except
for the aromatic and aliphatic moieties, which exhib-
ited 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 car-
boxylic acid 4, 2-oxopropyl benzoate (or acetate) 3,
and primary amine 5 that leads to an intermediate
iminium ion 9. The nucleophilic addition of the (N-
isocyanimino)triphenylphosphorane 6 to the inter-
mediate iminium ion 9 leads to nitrilium interme-
diate 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 disub-
stituted 1,3,4-oxadiazole 7 by the removal of triph-
enylphosphine oxide 8 from intermediate 12.
CONCLUSIONS
2-(Benzylamino)-2-[5-(3,5-dimethylphenyl)- 1,3,
4-oxadiazol-2-yl]propyl benzoate (7a). Yellow oil,
yield: 375 mg (85%). 1H NMR: 1.83, 2.36 (s, 9H,
3CH3); 2.08 (s, 1H, NH of amine exchangeable by
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 acetate) 3, primary amine 5,
(N-isocyanimino)triphenylphosphorane 6, and aro-
matic carboxylic acid 4. Its ease of work-up, high
yields, and fairly mild reaction conditions make it a
useful addition to modern synthetic methodologies.
2
D2O); 3.74, 3.83 (AB quartet, 2H, JHH = 12.37 Hz,
CH2 of the benzyl group); 4.60, 4.73 (AB quar-
2
tet, 2H, JHH = 10.87 Hz, CH2 aliphatic); 7.15–
8.01 (m, 13H, H-Ar).13C NMR: 20.97, 21.21 (3CH3);
47.80 (CH2 of the benzyl group); 56.79 (C aliphatic);
69.20 (CH2 aliphatic); 129.45, 133.33, 133.55, 138.79
(5C arom); 123.42, 124.28, 127.28, 128.25, 128.49,
128.55, 129.71, 129.90 (13CH arom); 165.58, 165.83
(2C of oxadiazole); 168.21 (C of the benzoate group).
IR (neat): 3467, 2961, 2364, 2354, 1726, 1430, 1273,
712 cm−1. Anal. calcd for C27H27N3O3 (441.52): C
73.45, H 6.16, N 9.52; Found: C 73.40, H 6.12, N 9.55.
MS (EI): 441 (M+), 279 (3.67), 174 (9.77), 167 (21.20),
149 (89.29), 132 (29.75), 104 (89.27), 91 (27.20), 76
(79.92), 57 (97.95), 43 (100).
EXPERIMENTAL
Starting materials and solvents were obtained from
Merck (Darmstadt, Germany) and Fluka (Buchs,
Switzerland) and were used without further purifi-
cation. The methods used to follow the reactions
are TLC and NMR, which indicated that there is no
side product. Melting points (mp) were measured on
an Electrothermal 9100 apparatus and are uncor-
Heteroatom Chemistry DOI 10.1002/hc

A One-Pot Efficient Four-Component Reaction for the Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives 695
SCHEME 2 Proposed mechanism for the formation of disubstituted 1,3,4-oxadiazole derivatives 7a–m.
H-Ar).13C NMR: 19.75, 20.05, 20.89, 21.07 (4CH3);
47.56 (CH2 of the benzyl group); 56.79 (C aliphatic);
69.25 (CH2 aliphatic); 129.41, 130.24, 133.33, 137.03,
137.53, 141.13 (6C arom); 121.14, 124.45, 127.88,
128.32, 128.48, 129.21, 129.59, 129.72 (12CH arom);
165.55, 165.82 (2C of oxadiazole); 167.89 (C of the
benzoate group). IR (neat): 3467, 2952, 2417, 2377,
1725, 1452, 1271, 1114, 715 cm−1. Anal. calcd for
C28H29N3O3 (455.22): C 73.82, H 6.42, N 9.22; Found:
C 73.78, H 6.46, N 9.17.
2-[5-(3,5-Dimethylphenyl)-1,3,4-oxadiazol-2-yl]-
2-[(4-methylbenzyl)amino)]propyl Benzoate (7b).
Yellow oil, yield: 396 mg (87%). 1H NMR: 1.87,
2.24, 2.36 (s, 12H, 4CH3); 2.12 (s, 1H, NH of amine);
3.75, 3.85 (AB quartet, 2H, 2 JHH = 12 Hz, CH2 of the
2
benzyl group); 4.66, 4.76 (AB quartet, 2H, JHH
=
11 Hz, CH2 aliphatic); 7.06–8.02 (m, 12H, H-Ar).13C
NMR: 21.02, 21.12, 21.21 (4CH3); 47.54 (CH2 of
the benzyl group); 56.95 (C aliphatic); 69.45 (CH2
aliphatic); 129.43, 133.33, 133.55, 137.09, 138.76
(6C arom); 123.33, 124.67, 128.41, 128.47, 129.21,
129.72, 129.75 (12CH arom); 165.64, 165.76 (2C of
oxadiazole); 167.78 (C of the benzoate group). IR
(neat): 3495, 2427, 2369, 1728, 1459, 1279,1118, 716
cm−1. Anal. calcd for C28H29N3O3 (455.22): C 73.82,
H 6.42, N 9.22; Found: C 73.88, H 6.47, N 9.18. MS
(EI): 455.55 (M+), 174 (1.06), 105 (4.82), 58 (14.63),
43 (100).
2-(Benzylamino)-2-[5-(3,4-dimethylphenyl)- 1,3,
4-oxadiazol-2-yl]propyl Benzoate (7d). Yellow oil,
yield: 380 mg (86%). 1H NMR: 1.84, 2.31, 2.32
(s, 9H, 3CH3); 2.10 (s, 1H, NH of amine); 3.79,
2
3.88 (AB quartet, 2H, JHH = 12.37 Hz, CH2 of the
2
benzyl group); 4.65, 4.75 (AB quartet, 2H, JHH
=
11 Hz, CH2 aliphatic); 7.22–8.08 (m, 13H, H-Ar).13C
NMR: 19.73, 20.03, 20.83 (3CH3); 47.82 (CH2 of
the benzyl group); 56.91 (C aliphatic); 69.23 (CH2
aliphatic); 129.48, 130.26, 133.33, 137.55, 141.18
(5C arom); 121.09, 124.47, 127.42, 127.89, 128.48,
128.53, 128.64, 129.33, 129.72 (13CH arom); 165.60,
165.80 (2C of oxadiazole); 168.72 (C of the benzoate
group). IR (neat): 3441, 2956, 2369, 2359, 1725, 1453,
1272, 1115, 711 cm−1. Anal. calcd for C27H27N3O3
2-[5-(3,4-Dimethylphenyl)- 1,3,4-oxadiazol-2-yl]-
2-[(4-methylbenzyl)amino)]propyl Benzoate (7c).
Yellow oil, yield: 373 mg (82%). 1H NMR: 1.82,
2.25, 2.31 (s, 12H, 4CH3); 2.10 (s, 1H, NH of amine);
2
3.71, 3.81 (AB quartet, 2H, JHH = 11.37 Hz, CH2
of the benzyl group); 4.62, 4.71 (AB quartet, 2H,
2 JHH = 10.12 Hz, CH2 aliphatic); 7.09–8.07 (m, 12H,
Heteroatom Chemistry DOI 10.1002/hc

696 Ramazani et al.
(441.52): C 73.45, H 6.16, N 9.52; Found: C 73.41, H
6.11, N 9.56.
2-[5-(3,5-Dimethylphenyl)-1,3,4-oxadiazol-2-yl]-
2-[(4-fluorobenzyl)amino]propyl
Benzoate
(7h).
Yellow oil, yield: 386 mg (84%). 1H NMR: 1.84,
2.36 (s, 9H, 3CH3); 2.08 (s, 1H, NH of amine);
2-(Benzylamino)-2-[5-(3,5-dimethylphenyl)-1,3,
4-oxadiazol-2-yl]propyl Acetate (7e). Yellow oil,
yield: 330 mg (87%). 1H NMR: 1.72, 2.04, 2.40
(s, 9H, 3CH3); 2.11 (s, 1H, NH of amine); 3.75 (s, 2H,
CH2 of the benzyl group); 4.35, 4.53 (AB quartet,
2H, 2 JHH = 11 Hz, CH2 aliphatic); 7.17–7.65 (m, 8H,
H-Ar).13C NMR: 20.72, 20.92, 21.18.80 (4CH3); 47.77
(CH2 of the benzyl group); 56.54 (C aliphatic); 68.67
(CH2 aliphatic); 133.51, 138.82, 139.71 (4C arom);
123.54, 124.63, 127.21, 128.23, 128.47 (8CH arom);
165.78, 167.74 (2C of oxadiazole); 170.34 (C of the
benzoate group). IR (neat): 3339, 2929, 1754, 1455,
1249, 1051, 741 cm−1. Anal. calcd for C22H25N3O3
(379.45): C 69.64, H 6.64, N 11.07; Found: C 69.60,
H 6.73, N 11.11.
2
3.73, 3.79 (AB quartet, 2H, JHH = 12.25 Hz, CH2
of the benzyl group); 4.58, 4.72 (AB quartet, 2H,
2 JHH = 11 Hz, CH2 aliphatic); 6.93–8.01 (m, 12H,
H-Ar).13C NMR: 20.95, 21.20 (3CH3); 47.06 (CH2 of
the benzyl group); 56.82 (C aliphatic); 69.21 (CH2
aliphatic); 115.33 (d,2 JCF = 21.39 Hz, 2CH, arom),
129.83 (d,3 JCF = 8.8 Hz, 2CH, arom), 124.64, 128.50,
129.69, 129.72, 130.02 (8CH arom); 129.79, 133.39,
133.65, 138.83 (4C arom); 162.81 (d,1 JCF = 212.17
Hz, C, arom), 165.62, 165.79 (2C of oxadiazole);
167.83 (C of the benzoate group). IR (neat): 3471,
2380, 2373, 1725, 1509, 1273, 1117, 713 cm−1. Anal.
calcd for C27H26FN3O3 (459.51): C 70.57, H 5.70, N
9.14; Found: C 70.53, H 5.74, N 9.10.
2- [5- (2- Bromophenyl)- 1,3,4- oxadiazol- 2- yl]- 2-
[(4-fluorobenzyl)amino]propyl Benzoate (7i). Yel-
low oil, yield: 413 mg (81%). 1H NMR: 1.82
(s, 3H, CH3); 2.07 (s, 1H, NH of amine); 3.82 (s, 2H,
CH2 of the benzyl group); 4.61, 4.72 (AB quartet,
2 -(Benzylamino)-2-[5-(4-methylphenyl)-1,3,4-
oxadiazol-2-yl]propyl Acetate (7f). Yellow oil, yield:
321 mg (88%). 1H NMR: 1.67, 2.04, 2.43 (s, 9H,
3CH3); 2.06 (s, 1H, NH of amine); 3.72, 3.78
2
(AB quartet, 2H, JHH = 12.37 Hz, CH2 of the ben-
2
zyl group); 4.33, 4.51 (AB quartet, 2H, 2 JHH = 11 Hz,
CH2 aliphatic); 7.23–7.94 (m, 9H, H-Ar).13C NMR:
20.80, 20.91, 21.68 (3CH3); 47.79 (CH2 of the benzyl
group); 56.48 (C aliphatic); 68.76 (CH2 aliphatic);
120.97, 139.65, 142.41 (3C arom); 126.87, 127.25,
128.28, 128.51, 129.78 (9CH arom); 165.33, 167.64
(2C of oxadiazole); 170.42 (C of the benzoate group).
IR (neat): 3468, 2969, 2374, 2360, 1726, 1489, 1276,
1115, 717 cm−1. Anal. calcd for C21H23N3O3 (365.43):
C 69.02, H 6.34, N 11.50; Found: C 69.07, H 6.29, N
11.47.
2H, JHH = 10.87 Hz, CH2 aliphatic); 6.99–7.90 (m,
13H, H-Ar).13C NMR: 21.05 (CH3); 47.07 (CH2 of
the benzyl group); 56.88 (C aliphatic); 69.18 (CH2
aliphatic); 115.29 (d,2 JCF = 20.80 Hz, 2CH, arom),
129.86 (d,3 JCF = 8.1 Hz, 2CH, arom), 127.66, 128.48,
129.35, 129.69, 129.73, 132.74, 133.35 (9CH arom);
121.61, 131.74, 132.70, 134.44 (4C arom); 162.03
(d,1 JCF = 244.7 Hz, C, arom), 164.29, 165.82 (2C of
oxadiazole); 168.62 (C of the benzoate group). IR
(neat): 3469, 2387, 2381, 1725, 1455, 1273, 1117,
716 cm−1. Anal. calcd for C25H21BrFN3O3 (510.35):
C 58.84, H 4.15, N 8.23; Found: C 58.88, H 4.10, N
8.27.
2-[(4-Methylbenzyl)amino)]2-[5-(4-methylpheny-
l)-1,3,4-oxadiazol-2-yl]propyl Benzoate (7g). Yellow
oil, yield: 375 mg (85%). IR (neat): 3461, 2961, 2381,
2-(Benzylamino)-2-[5-(4-bromophenyl)-1,3,4-
1
2366, 1725, 1499, 1271, 1115, 713 cm−1. H NMR:
oxadiazol-2-yl]propyl Benzoate (7j). Yellow oil,
1
1.84, 2.25, 2.43 (s, 9H, 3CH3); 2.09 (s, 1H, NH of
yield: 423 mg (86%). H NMR: 1.83 (s, 3H, CH3);
2
amine); 3.74, 3.83 (AB quartet, 2H, JHH = 12 Hz,
2.18 (s, 1H, NH of amine exchangeable by D2O);
3.82 (s, 2H, CH2 of the benzyl group); 4.62, 4.73 (AB
quartet, 2H, 2 JHH = 11 Hz, CH2 aliphatic); 7.24–7.99
(m, 14H, H-Ar).13C NMR: 21.00 (CH3); 47.78 (CH2
of the benzyl group); 56.86 (C aliphatic); 69.00 (CH2
aliphatic); 121.81, 129.36, 133.40, 137.20 (4C arom);
122.57, 126.54, 127.33, 128.25, 128.32, 128.52,
129.68, 132.37 (14CH arom); 164.56, 165.78 (2C of
oxadiazole); 168.02 (C of the benzoate group). IR
(neat): 3485, 2411, 2369, 1726, 1482, 1273, 1115,
712 cm−1. Anal. calcd for C25H22BrN3O3 (492.36):
C 60.98, H 4.50, N 8.53; Found: C 60.93, H 4.53,
N 8.50.
CH2 of the benzyl group); 4.65, 4.73 (AB quartet,
2H, 2 JHH = 11 Hz, CH2 aliphatic); 7.06–8.0 (m, 13H,
H-Ar).13C NMR: 20.85, 21.04, 21.67 (3CH3); 47.56
(CH2 of the benzyl group); 56.86 (C aliphatic); 69.31
(CH2 aliphatic); 129.40, 133.31, 133.55, 137.09,
142.38 (5C arom); 120.89, 126.90, 128.37, 128.47,
129.21, 129.72, 129.79 (13CH arom); 165.43, 165.43
(2C of oxadiazole); 167.80 (C of the benzoate group).
IR (neat): 3468, 2969, 2374, 2360, 1726, 1489, 1276,
1115, 717 cm−1. Anal. calcd for C27H27N3O3 (441.52):
C 73.45, H 6.16, N 9.52; Found: C 73.48, H 6.12, N
9.57.
Heteroatom Chemistry DOI 10.1002/hc

A One-Pot Efficient Four-Component Reaction for the Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives 697
2 - (Benzylamino) - 2- [5- (4- chlorophenyl) -1,3,4-
oxadiazol-2-yl]propyl Benzoate (7k). Yellow oil,
ACKNOWLEDGMENT
This work was supported by Zanjan University,
Zanjan, Iran.
yield: 380 mg (85%). IR (neat): 3472, 2387, 2385,
1
1726, 1484, 1273, 1095, 712 cm−1. H NMR: 1.83
(s, 3H, CH3); 2.24 (s, 1H, NH of amine); 3.78, 3.86
(AB quartet, 2H, 2 JHH = 12.37 Hz, CH2 of the benzyl
REFERENCES
2
group); 4.63, 4.74 (AB quartet, 2H, JHH = 11 Hz,
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CH2 aliphatic); 7.21–8.09 (m, 14H, H-Ar).13C NMR:
21.01 (CH3); 47.79 (CH2 of the benzyl group); 56.85
(C aliphatic); 69.02 (CH2 aliphatic); 122.16, 129.38,
133.40, 138.09 (4C arom); 127.32, 128.20, 128.22,
128.49, 128.52, 129.38, 129.42, 129.68 (14CH arom);
164.47, 165.79 (2C of oxadiazole); 168.03 (C of
the benzoate group). IR (neat): 3485, 2411, 2369,
1726, 1482, 1273, 1115, 712 cm−1. Anal. calcd for
C25H22ClN3O3 (447.91): C 67.04, H 4.95, N 9.38;
Found: C 67.07, H 4.90, N 9.35.
2 - [5 - (4 - Chlorophenyl) - 1,3,4 - oxadiazol - 2 - yl]-
2-[(4-methoxybenzyl)amino]propyl Benzoate (7l).
Yellow oil, yield: 396 mg (83%). 1H NMR: 1.81
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[8] Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197.
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Mol Divers 2011, 15, 521–527.
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21, 4263.
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L. Inorg Chem 2005, 44, 6425.
[14] Yavari, I.; Ramazani, A.; Yahya-Zadeh, A. Synth Com-
mun 1996, 26, 4495.
(s, 3H, CH3); 2.07 (s, 1H, NH of amine); 3.73 (s,
2
3H, OCH3); 3.68, 3.78 (AB quartet, 2H, JHH
=
12.12 Hz, CH2 of the benzyl group); 4.60, 4.71
2
(AB quartet, 2H, JHH = 11 Hz, CH2 aliphatic);
6.72–8.07 (m, 13H, H-Ar).13C NMR: 21.03 (CH3);
47.18 (CH2 of the benzyl group); 55.21 (OCH3); 56.69
(C aliphatic); 69.09 (CH2 aliphatic); 129.72, 131.60,
133.28, 133.37, 158.78 (5C arom); 113.87, 124.17,
128.16, 128.50, 129.39, 129.65, 129.72 (13CH arom);
165.55, 165.78 (2C of oxadiazole); 168.27 (C of the
benzoate group). IR (neat): 3476, 2989, 2389, 2378,
1729, 1480, 1276, 1115, 715 cm−1. Anal. calcd for
C26H24ClN3O4 (477.94): C 65.34, H 5.06, N 8.79;
Found: C 65.29, H 5.10, N 8.83.
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Relat Elem 1997, 130, 73.
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567.
[17] Pakravan, P.; Ramazani, A.; Noshiranzadeh, N.;
Sedrpoushan, A. Phosphorus, Sulfur, Silicon Relat
Elem 2007, 182, 545.
[18] Ramazani, A.; Rahimifard, M.; Souldozi, A. Phospho-
rus, Sulfur, Silicon Relat Elem 2007, 182, 1.
[19] Ramazani, A.; Rahimifard, M.; Noshiranzadeh, N.;
Souldozi, A. Phosphorus, Sulfur, Silicon Relat Elem
2007, 182, 413.
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Dolatyari, L.; Noshiranzadeh, N.; Eskandari, I.;
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Sulfur, Silicon Relat Elem 2001, 176, 223.
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Sulfur, Silicon Relat Elem 2006, 181, 2225.
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R. Tetrahedron Lett 2007, 48, 2617.
2-[5-(3,5-Dimethylphenyl)-1,3,4-oxadiazol-2-yl]-
2-[(4-methoxybenzyl)amino]propyl Benzoate (7m).
Yellow oil, yield: 400 mg (85%). 1H NMR: 1.81, 2.35
(s, 9H, 3CH3); 2.10 (s, 1H, NH of amine); 3.73 (s, 3H,
OCH3); 3.68, 3.78 (AB quartet, 2H, 2 JHH = 12.12 Hz,
CH2 of the benzyl group); 4.59, 4.71 (AB quartet,
2
2H, JHH = 10.89 Hz, CH2 aliphatic); 6.76-8.08 (m,
12H, H-Ar).13C NMR: 20.99, 21.20 (3CH3); 47.20
(CH2 of the benzyl group); 55.22 (OCH3); 56.66
(C aliphatic); 69.21 (CH2 aliphatic); 131.72, 133.31,
133.52, 138.78, 158.77 (6C arom); 113.87, 124.62,
128.47, 129.43, 129.47, 129.70, 129.78 (12CH arom);
165.54, 165.84 (2C of oxadiazole); 167.94 (C of the
benzoate group). IR (neat): 3472, 2377, 2369, 1479,
1281, 1116, 715 cm−1. Anal. calcd for C28H29N3O4
(471.55): C 71.32, H 6.20, N 8.91; Found: C 71.36, H
6.16, N 8.88.
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Slepokura, K.; Lis, T. Helv Chim Acta 2008, 91,
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M.; Khoobi, M. Helv Chim Acta 2010, 93, 2033.
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Heteroatom Chemistry DOI 10.1002/hc