The reaction of N-isocyaniminotriphenylphosphorane with ester derivatives of 2-oxopropyl alcohol (2-Oxopropyl 4-Bromobenzoate, 2-Oxopropyl Benzoate, and 2-Oxopropyl Acetate) in the presence of aromatic carboxylic acids: A one-pot efficient three-component reaction for the synthesis of fully substituted 1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1002/jhet.1012

Reactions of N-isocyaniminotriphenylphosphorane with ester derivatives of 2-oxopropyl alcohol (2-oxopropyl 4-bromobenzoate, 2-oxopropyl benzoate, and 2-oxopropyl acetate) in the presence of aromatic carboxylic acids 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.1012

November 2012
The Reaction of N‐Isocyaniminotriphenylphosphorane with Ester
Derivatives of 2‐Oxopropyl Alcohol (2‐Oxopropyl
1447
4‐Bromobenzoate, 2‐Oxopropyl Benzoate, and 2‐Oxopropyl
Acetate) in the Presence of Aromatic Carboxylic Acids: A
One‐Pot Efficient Three‐Component Reaction for the Synthesis of
Fully Substituted 1,3,4‐Oxadiazole Derivatives
a
a
a
b
*
Ali Ramazani, Yavar Ahmadi, Zahra Karimi, and Aram Rezaei
aChemistry Department, Zanjan University, Zanjan 45195‐313, Iran
bYoung Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran
*
E-mail: aliramazani@gmail.com
Received March 13, 2011
DOI 10.1002/jhet.1012
View this article online at wileyonlinelibrary.com.
Reactions of N‐isocyaniminotriphenylphosphorane with ester derivatives of 2‐oxopropyl alcohol (2‐oxopropyl 4‐
bromobenzoate, 2‐oxopropyl benzoate, and 2‐oxopropyl acetate) in the presence of aromatic carboxylic
acids 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 condi-
tions and no side reactions were observed.
J. Heterocyclic Chem., 49, 1447 (2012).
INTRODUCTION
to possess a wide range of pharmacological and therapeutic ac-
tivities. Some 1,3,4‐oxadiazoles have exhibited analgesic, anti‐
inflammatory, anticonvulsant, tranquilizing, myorelaxant, anti-
depressant, vasodilatatory, diuretic, antiulcer, antiarythmic,
antiserotoninic, spasmolytic, hypotensive, antibronchocontric-
tive, anticholinergic, and antiemetic activities. Furthermore,
many 1,3,4‐oxadiazole derivatives have been reported as active
inhibitors of several enzymes [5], [6].
The intramolecular version of the aza‐Wittig‐type reaction
has attracted considerable attention recently because of its high
potential for the synthesis of a wide variety of nitrogen hetero-
cycles, which can be attributed, in good measure, to the rapid
progress in the preparation of functionalized iminophosphor-
anes. The nucleophilicity at the nitrogen is a factor of essential
mechanistic importance 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 pharmacological activity [7–11]. However, the
organic chemistry of N‐isocyaniminotriphenylphosphorane 5
remains almost unexplored. N‐isocyaniminotriphenylpho-
sphorane 5 is expected to have synthetic potential because it
provides a reaction system in which the iminophosphorane
group can react with a reagent having a carbonyl functionality
[12], [13]. In recent years, we have established a one‐pot
method for the synthesis of organophosphorus compounds
[14–22]. As part of our ongoing program to develop efficient
Multicomponent reactions (MCRs) have emerged as an
efficient and powerful tool in modern synthetic organic
chemistry because of their valued features such as atom
economy, straightforward reaction design, and the opportunity
to construct target compounds by the introduction of several
diversity elements in a single chemical event. Typically,
purification of products resulting from MCR is also simple
because all the organic reagents used are consumed and are
incorporated into the target compound [1]. MCRs, leading to
interesting heterocyclic scaffolds, are particularly useful for
the construction of diverse chemical libraries of “drug‐like”
molecules. The isocyanide‐based MCRs are especially impor-
tant in this area [2], [3].
Among the known multicomponent reactions to date,
the most valuable reactions are those based on isocyanides.
Isocyanide‐based multicomponent reactions (abbreviated
to IMCRs by Ugi and Dömling) by virtue of their synthetic
potential, their inherent atom efficiency, convergent nature,
ease of implementation, and the generation of molecular
diversity have attracted much attention because of the
advantages that they offer to the field of combinatorial
chemistry [4].
During recent years, there has been considerable investiga-
tion on different classes of oxadiazoles. In particular, com-
pounds containing 1,3,4‐oxadiazole nucleus have been shown
© 2012 HeteroCorporation

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A. Ramazani, Y. Ahmadi, Z. Karimi, and A. Rezaei
Vol 49
Scheme 1. Synthesis of ester derivatives of 2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate, 2‐oxopropyl benzoate, and 2‐oxopropyl acetate) and
three‐component synthesis of disubstituted 1,3,4‐oxadiazole derivatives 6a–m (see Experimental part).
and robust methods for the preparation of heterocyclic com-
pounds [23–35], we wish to report the synthesis of a disubsti-
tuted 1,3,4‐oxadiazole derivatives 6 by a three‐component
condensation of N‐isocyaniminotriphenylphosphorane 5, aro-
matic carboxylic acid derivatives, and ester derivatives of 2‐
oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate, 2‐oxo-
propyl benzoate, and 2‐oxopropyl acetate) (Scheme 1).
which exhibited characteristic signals with appropriate
chemical shifts.
The suggested mechanism for the formation of products
6a–m is illustrated in Scheme 2. On the basis of the
chemistry of isocyanides, it is reasonable to assume that
the first step may involve nucleophilic addition of the
N‐isocyaniminotriphenylphosphorane 5 to ester derivative
of 2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate,
2‐oxopropyl benzoate, and 2‐oxopropyl acetate), which
facilitates by its protonation with the acid, leading to nitrilium
intermediate 8. This intermediate may be attacked by
conjugate base of the acid to form 1:1:1 adduct 9. This
adduct may undergo intramolecular aza‐Wittig reaction
of iminophosphorane moiety with the ester carbonyl to
afford the isolated sterically congested 1,3,4‐oxadiazole
derivatives 6 by removal of triphenylphosphine oxide
from intermediate 10.
RESULTS AND DISCUSSION
The carboxylic acid derivative with ester derivatives of
2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate,
2‐oxopropyl benzoate, and 2‐oxopropyl acetate), and
N‐isocyaniminotriphenylphosphorane 5 in CH2Cl2 react
together in a 1:1:1 ratio at room temperature to produce disub-
stituted 1,3,4‐oxadiazole derivatives and triphenylphosphine
oxide (Scheme 1). The reaction proceeds smoothly and cleanly
under mild conditions and no side reactions were observed.6a:
R = Ph, Ar = 3,5‐diMeC6H4; 6b: R = Ph, Ar = 4‐MeC6H4;
6c: R = Ph, Ar = 3,4‐diMeC6H4; 6d: R = Ph, Ar = 4‐ClC6H4;
6e: R = Ph, Ar = 4‐BrC6H4; 6f: R = CH3, Ar = 3‐MeC6H4;
6g: R = Ph, Ar = 3‐MeC6H4; 6h: R = Ph, Ar = 4‐EtC6H4;
6i: R = CH3, Ar = 4‐MeC6H4; 6j: R = 4‐BrC6H4,
Ar = 4‐ClC6H4; 6k: R = 4‐BrC6H4, Ar = 4‐BrC6H4;
6l: R = 4‐BrC6H4, Ar = 4‐MeC6H4; 6m: R = 4‐BrC6H4,
Ar = 3‐ClC6H4
CONCLUSIONS
We believe that the reported method offers a mild, simple,
and efficient route for the preparation of sterically congested
1,3,4‐oxadiazole derivatives 6 from ester derivatives of
2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate,
2‐oxopropyl benzoate, and 2‐oxopropyl acetate), N‐isocyani-
minotriphenylphosphorane 5. and aromatic carboxylic acids.
Its ease of work‐up, high yields, and fairly mild reaction
conditions make it a useful addition to modern synthetic
methodologies.
The structures of the products were deduced from their
1H‐NMR, 13C‐NMR, Mass and IR spectra. For example,
1
the H‐NMR spectrum of 6a consisted of two singlet for
the 3 CH3 (δ = 1.85 and 2.33 ppm), a broad singlet for
the OH (δ = 4.36), a AB‐quartet for CH2 aliphatic at
δ = 4.65 and 4.71 ppm (J = 11.50 Hz), and a multiplet
at δ = 7.12–7.99 ppm for H‐aromatic. The aryl groups
exhibited characteristic signals in the aromatic region
of the spectrum. The 1H decoupled 13C‐NMR spectrum
of 6a showed 15 distinct resonances; partial assignment of
these resonances is given in the experimental section. The
1H‐ and 13C‐NMR spectra of compounds 6b–m were similar
to those of 6a, except for the aromatic and aliphatic moieties,
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 point
were measured on an Electrothermal 9100 apparatus and are
uncorrected. IR spectra were measured on a Jasco 6300 FTIR
spectrometer. 1H‐ and 13C‐NMR spectra were measured (CDCl3)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2012
The Reaction of N‐Isocyaniminotriphenylphosphorane with Ester Derivatives of 2‐Oxopropyl
Alcohol (2‐Oxopropyl 4‐Bromobenzoate, 2‐Oxopropyl Benzoate, and 2‐Oxopropyl Acetate)
1449
Scheme 2. Proposed mechanism for the formation of disubstituted 1,3,4‐oxadiazole derivatives 6a–m.
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
operating at an ionization potential of 70 eV. Flash chromatography
columns were prepared with Merck silica gel. Ester derivatives of
2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate, 2‐oxopropyl
benzoate, and 2‐oxopropyl acetate) were prepared based on known
procedure [36].
(352.38): C, 68.17; H, 5.72; N, 7.95. Found: C, 68.13; H,
5.77; N 7.92
2‐Hydroxy‐2‐[5‐(4‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]propyl
benzoate (6b). This compound was obtained as white crystals, the
yield was 287 mg (85%), m.p. 115.6–116.9°, IR (KBr): 3317,
1
2954, 1728, 1500, 1282, 711 cm−1. H‐NMR (CDCl3): δ 1.84,
2.41 (s, 6H, 2CH3), 4.0 (br s, 1H, OH), 4.63, 4.72 (AB quartet, J
= 11.37 Hz, 2H, CH2 aliphatic), 7.29–7.99 (m, 9H, H‐Ar). 13C‐
NMR (CDCl3): δ 21.69, 23.51 (2CH3), 69.83 (C aliphatic), 70.43
(CH2 aliphatic), 120.59, 129.10, 142.62 (3C arom), 126.95,
128.49, 129.78, 129.81, 133.50 (9CH arom), 165.64, 166.15 (2C
of oxadiazole), 167.75 (C of benzoate group). EI ms: m/z: 338
(M+), 203 (18.08), 166 (83.81), 149 (64.30), 122 (31.18), 105
(72.16), 91 (27.54), 77 (72.66), 57 (62.76), 43 (100). Anal.
Calcd. for C19H18N2O4 (338.36): C, 67.44; H, 5.36; N, 8.28.
Found: C, 67.48; H, 5.33; N, 8.32.
2‐[5‐(3,4‐Dimethylphenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl
benzoate (6c). This compound was obtained as yellow oil, the yield
was 303mg (86%), IR (neat): 3450, 2953, 1726, 1453, 1274, 713 cm−1.
1H‐NMR (CDCl3): δ 1.84, 2.28, 2.30 (s, 9H, 3CH3), 4.22 (br s, 1H,
OH), 4.64, 4.71 (AB quartet, J = 11.37 Hz, 2H, CH2 aliphatic),
7.19–7.99 (m, 8H, H‐Ar). 13C‐NMR (CDCl3): δ 19.69, 20.02, 23.52
(3CH3), 69.83 (C aliphatic), 70.38 (CH2 aliphatic), 120.83, 129.15,
137.55, 141.33 (4C arom), 124.51, 127.92, 128.46, 129.78, 130.24,
130.44 (8CH arom), 165.72, 166.20 (2C of oxadiazole), 167.57 (C
of benzoate group). Anal. Calcd. for C20H20N2O4 (352.38): C,
68.17; H, 5.72; N, 7.95. Found: C, 68.20; H, 5.76; N, 7.90.
General procedure for the preparation of 6a–m. A mixture
of N‐isocyaniminotriphenylphosphorane 5 (1 mmol, 0.302 g), ester
derivative of 2‐oxopropyl alcohol 3 (2‐oxopropyl 4‐bromobenzoate,
2‐oxopropyl benzoate, and 2‐oxopropyl acetate) [1 mmol; 0.116 g
(R = CH3), 0.178 g (R = Ph), and 0.257 g (R = 4‐BrC6H4)], and
carboxylic acid [1 mmol; 0.150 g (Ar = 3,5‐diMeC6H4), 0.136 g
(Ar = 4‐MeC6H4), 0.150 g (Ar = 3,4‐diMeC6H4), 0.157 g
(Ar = 4‐ClC6H4), 0.201 g (Ar = 4‐BrC6H4), 0.136 g (Ar = 3‐MeC6H4),
0.150 g (Ar = 4‐EtC6H4), and 0.157 g (Ar = 3‐ClC6H4)] in
CH2Cl2 (5 mL) was stirred at room temperature for 1 h. Then,
the solvent was removed under reduced pressure and the
viscous residue was purified by flash column chromatography
[silica gel; petroleum ether–ethyl acetate (4:1)]. The solvent
was removed under reduced pressure to give product 6. The
characterization data of the compounds are given below.
2‐[5‐(3,5‐Dimethylphenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl
benzoate (6a). This compound was obtained as yellow oil, the yield
was 306 mg (87%), IR (neat): 3490, 1725, 1274, 714 cm−1
.
1H‐NMR (CDCl3): δ 1.85, 2.33 (s, 9H, 3CH3), 4.36 (br s, 1H, OH),
4.65, 4.71 (AB quartet, J = 11.50 Hz, 2H, CH2 aliphatic),
7.12–7.99 (m, 8H, H‐Ar). 13C‐NMR (CDCl3): δ 21.16, 23.53
(3CH3), 69.82 (C aliphatic), 70.35 (CH2 aliphatic), 123.09,
129.18, 138.77 (4C arom), 124.68, 128.44, 129.77, 133.42,
133.69 (8CH arom), 165.74, 166.19 (2C of oxadiazole),
167.76 (C of benzoate group). EI ms: m/z: 352 (M+), 217
(13.55), 167 (17.47), 149 (85.35), 132 (23.59), 104 (100), 91
(33.43), 77 (72.80), 43 (91.28). Anal. Calcd. for C20H20N2O4
2‐[5‐(4‐Chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl
benzoate (6d). This compound was obtained as white crystals, the
yield was 293 mg (82%), m.p. 123.3–124.7°, IR (KBr): 3397,
2953, 1726, 1607, 1486, 1281, 708 cm−1. 1H‐NMR (CDCl3):
δ 1.84 (s, 3H, CH3), 3.87 (br s, 1H, OH), 4.64, 4.72 (AB quartet,
J = 11.37 Hz, 2H, CH2 aliphatic), 7.30–7.98 (m, 9H, H‐Ar).
13C‐NMR (CDCl3): δ 23.52, (CH3), 69.75 (C aliphatic), 70.45
(CH2 aliphatic), 121.86, 129.04, 138.29 (3C arom), 128.26,
128.51, 129.44, 129.76, 133.57 (9CH arom), 165.66, 166.22 (2C
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A. Ramazani, Y. Ahmadi, Z. Karimi, and A. Rezaei
Vol 49
of oxadiazole), 167.98 (C of benzoate group). Anal. Calcd. for
C18H15ClN2O4 (358.07): C, 60.26; H, 4.21; N, 7.81. Found: C,
60.29; H, 4.17; N, 7.85.
C14H16N2O4 (276.29): C, 60.86; H, 5.84; N, 10.14. Found: C,
60.81; H, 5.88; N, 10.11.
2‐[5‐(4‐Chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl 4‐
bromobenzoate (6j). This compound was obtained as white crystals,
the yield was 376 mg (86%), m.p. 168.3–169.8°, IR (KBr): 3386,
1725, 1621, 1467, 1256, 711 cm−1. 1H‐NMR (CDCl3): δ 1.83
(s, 3H, CH3), 3.30 (br s, 1H, OH), 4.62, 4.72 (AB quartet, J = 11.12
Hz, 2H, CH2 aliphatic), 7.47 (d, J = 7.75 Hz, 2H, H‐Ar), 7.53
(d, J = 7.87 Hz, 2H, H‐Ar), 7.82 (d, J = 7.75 Hz, 2H, H‐Ar),
7.95 (d, J = 7.87 Hz, 2H, H‐Ar).13C‐NMR (CDCl3): δ 23.86
(CH3), 69.07 (C aliphatic), 69.60 (CH2 aliphatic), 122.51,
127.73, 128.14, 137.29 (4C arom), 128.79, 130.11, 131.69,
132.39 (8CH arom), 163.94, 165.02 (2C of oxadiazole), 168.81
(C of 4‐bromobenzoate group). Anal. Calcd. for C18H14BrClN2O4
(437.67): C, 49.40; H, 3.22; N, 6.40. Found: C, 49.44; H, 3.18; N,
6.43.
2‐[5‐(4‐Bromophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl 4‐
bromobenzoate (6k). This compound was obtained as white
crystals, the yield was 409 mg (85%), m.p. 173.4–174.7°, IR (KBr):
3352, 2991, 1727, 1556, 1487, 1266, 714 cm−1. 1H‐NMR (CDCl3):
δ 1.83 (s, 3H, CH3), 3.61 (br s, 1H, OH), 4.63, 4.72 (AB quartet, J
= 11.37 Hz, 2H, CH2 aliphatic), 7.55 (d, J = 8.50 Hz, 2H, H‐Ar),
7.67 (d, J = 8.50 Hz, 2H, H‐Ar), 7.83 (d, J = 8.50 Hz, 2H, H‐Ar),
7.88 (d, J = 8.5 Hz, 2H, H‐Ar).13C‐NMR (CDCl3): δ 23.85 (CH3),
69.06 (C aliphatic), 69.58 (CH2 aliphatic), 122.82, 126.21, 128.15,
138.12 (4C arom), 128.90, 131.69, 132.39, 133.02 (8CH arom),
164.06, 165.02 (2C of oxadiazole), 168.81 (C of 4‐bromobenzoate
group). Anal. Calcd. for C18H14Br2N2O4 (482.12): C, 44.84; H,
2.93; N, 5.81. Found: C, 44.79; H, 2.97; N, 5.84.
2‐Hydroxy‐2‐[5‐(4‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]propyl 4‐
bromobenzoate (6l). This compound was obtained as white
crystals, the yield was 350 mg (84%), m.p. 154.3–155.6°, IR (KBr):
3324, 2959, 1725, 1510, 1286, 714 cm−1. 1H‐NMR (CDCl3):
δ 1.70, 2.36 (s, 6H, 2CH3), 4.26 (br s, 1H, OH), 4.51, 4.60 (AB
quartet, J = 11.12 Hz, 2H, CH2 aliphatic), 7.10–7.85 (m, 8H, H‐Ar).
13C‐NMR (CDCl3): δ 21.58, 23.88 (2CH3), 68.99 (C aliphatic),
69.61(CH2 aliphatic), 120.88, 128.13, 128.87, 142.71 (4C arom),
126.92, 130.43, 131.69, 132.38 (8CH arom), 164.75, 165.01 (2C of
oxadiazole), 168.35 (C of 4‐bromobenzoate group). Anal. Calcd. for
C19H17BrN2O4 (417.25): C, 54.69; H, 4.11; N, 6.71. Found: C,
54.65; H, 4.07; N, 6.75.
2‐[5‐(3‐Chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl 4‐
bromobenzoate (6m). This compound was obtained as white
crystals, the yield was 376 mg (86%), m.p. 164.3–165.6°, IR (KBr):
3391, 1726, 1634, 1550, 1464, 1256, 710 cm−1. 1H‐NMR (CDCl3):
δ 1.84 (s, 3H, CH3), 3.36 (br s, 1H, OH), 4.63, 4.71 (AB quartet,
J = 11.37 Hz, 2H, CH2 aliphatic), 7.39–7.95 (m, 8H, H‐Ar).
13C‐NMR (CDCl3): δ 23.51 (CH3), 69.86 (C aliphatic), 70.45 (CH2
aliphatic), 124.95, 127.95, 128.81, 135.24 (4C arom), 125.08,
126.92, 130.47, 131.22, 131.90, 132.11 (8CH arom), 164.35,
165.47 (2C of oxadiazole), 168.06 (C of 4‐bromobenzoate group).
Anal. Calcd. for C18H14BrClN2O4 (437.67): C, 49.40; H, 3.22; N,
6.40. Found: C, 49.45; H, 3.25; N, 6.36.
2‐[5‐(4‐Bromophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl
benzoate (6e). This compound was obtained as white crystals, the
yield was 350 mg (87%), m.p. 138.1–139.8°, IR (KBr): 3377,
2954, 1725, 1601, 1281, 1081, 709 cm−1. 1H‐NMR (CDCl3):
δ 1.84 (s, 3H, CH3), 3.87 (br s, 1H, OH), 4.64, 4.72 (AB quartet,
J = 11.37 Hz, 2H, CH2 aliphatic), 7.30–7.98 (m, 9H, H‐Ar).
13C‐NMR (CDCl3): δ 23.52, (CH3), 69.74 (C aliphatic), 70.45
(CH2 aliphatic), 122.29, 126.76, 129.15 (3C arom), 128.38,
128.51, 129.76, 132.40, 133.57 (9CH arom), 165.64, 166.75 (2C
of oxadiazole), 168.79 (C of benzoate group). Anal. Calcd. for
C18H15BrN2O4 (403.23): C, 53.62; H, 3.75; N, 6.95. Found: C,
53.66; H, 3.77; N, 6.92.
2‐Hydroxy‐2‐[5‐(3‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]propyl
acetate (6f). This compound was obtained as yellow oil, the yield
was 243 mg (88%), IR (neat): 3491, 2967, 1748, 1555, 1246, 1052,
722 cm−1. 1H‐NMR (CDCl3): δ 1.75, 2.06, 2.42 (s, 9H, 3CH3), 4.11
(br s, 1H, OH), 4.36, 4.54 (AB quartet, J = 11.50 Hz, 2H, CH2
aliphatic), 7.36–7.85 (m, 4H, H‐Ar).13C‐NMR (CDCl3): δ 20.76,
21.35, 23.47 (3CH3), 69.28 (C aliphatic), 70.21 (CH2 aliphatic),
123.24, 139.03 (2C arom), 124.15, 127.50, 129.02, 132.87 (4CH
arom), 165.56, 167.72 (2C of oxadiazole), 170.80 (C of acetate
group). Anal. Calcd. for C14H16N2O4 (276.29): C, 60.86; H 5.84; N
10.14. Found: C, 60.83; H, 5.79; N, 10.18.
2‐Hydroxy‐2‐[5‐(3‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]propyl
benzoate (6g). This compound was obtained as yellow oil, the
yield was 287 mg (85%), IR (neat): 3327, 2964, 1726, 1448,
1
1255, 710 cm−1. H‐NMR (CDCl3): δ 1.84, 2.37 (s, 6H, 2CH3),
4.20 (br s, 1H, OH), 4.65, 4.71 (AB quartet, J = 11.87 Hz, 2H,
CH2 aliphatic), 7.32–7.98 (m, 9H, H‐Ar). 13C‐NMR (CDCl3):
δ 21.28, 23.53 (2CH3), 69.81 (C aliphatic), 70.37 (CH2
aliphatic), 123.22, 129.16, 138.93 (3C arom), 124.15, 127.47,
128.45, 128.93, 129.77, 132.78, 133.43 (9CH arom), 165.59,
166.19 (2C of oxadiazole), 167.89 (C of benzoate group). Anal.
Calcd. for C19H18N2O4 (338.36): C, 67.44; H, 5.36; N, 8.28.
Found: C, 67.47; H, 5.40; N, 8.24.
2‐[5‐(3‐Methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2‐hydroxypropyl
benzoate (6h). This compound was obtained as white crystals, the
yield was 295 mg (84%), m.p. 240.1–241.3°, IR (KBr): 3369,
1
2977, 1725, 1282, 1084, 706 cm−1. H‐NMR (CDCl3): δ 1.25
(t, J = 7.2 Hz, 3H, CH3 of Et), 1.84 (s, 3H, CH3), 2.69 (q,
J = 7.2 Hz, 2H, CH2 of Et), 4.18 (br s, 1H, OH), 4.64, 4.71
(AB quartet, 2H, J = 11.50 Hz, CH2 aliphatic), 7.29–7.98 (m,
9H, H‐Ar). 13C‐NMR (CDCl3): δ 15.16, 23.52 (2CH3), 28.89
(CH2 of Et), 69.79 (C aliphatic), 70.38 (CH2 aliphatic),
120.86, 129.23, 148.75 (3C arom), 127.07, 128.42, 128.53,
129.75, 133.36 (9CH arom), 165.59, 166.16 (2C of
oxadiazole), 167.66 (C of benzoate group). Anal. Calcd. for
C20H20N2O4 (352.38): C, 68.17; H, 5.72; N, 7.95. Found: C,
68.12; H, 5.75; N, 7.92.
2‐Hydroxy‐2‐[5‐(4‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]propyl
acetate (6i). This compound was obtained as yellow oil, the yield
was 229 mg (83%), IR (neat): 3473, 1748, 1501, 1255, 1052, 727
Acknowledgment. This work was supported by the “Zanjan
University.”
1
cm−1. H‐NMR (CDCl3): δ 1.74, 2.05, 2.42 (s, 9H, 3CH3), 4.11
(br s, 1H, OH), 4.36, 4.53 (AB quartet, J =11.12 Hz, 2H, CH2
aliphatic), 7.29 (d, J = 7.75 Hz, 2H, H‐Ar), 7.91 (d, J = 7.75 Hz,
2H, H‐Ar). 13C‐NMR (CDCl3): δ 20.76, 21.70, 23.47 (3CH3),
69.27 (C aliphatic), 70.16 (CH2 aliphatic), 120.60, 142.66 (2C
arom), 126.95, 129.80 (4CH arom), 165.54, 167.55 (2C of
oxadiazole), 170.79 (C of acetate group). Anal. Calcd. for
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