Microwave-Assisted Synthesis of 2-Amino and 2-Azetidinonyl 5-(2-Benzoyl-phenoxymethyl) 1,3,4-Oxadiazoles

Article abstract of DOI:10.1002/hc.10210

A simple high yielding method for the integration of heterocyclic rings viz. 1,3,4-oxadiazole and azetidin-2-one at the benzophenone nucleus has been developed starting from substituted 2-hydroxybenzophenones, and by using mild conditions, wet solid surfa

Full text of DOI:10.1002/hc.10210

Heteroatom Chemistry
Volume 15, Number 1, 2004
Microwave-Assisted Synthesis
of 2-Amino and 2-Azetidinonyl
5-(2-Benzoyl-phenoxymethyl)
1,3,4-Oxadiazoles
Shaukath Ara Khanum,2 S. Shashikanth,1 and B. S. Sudha2
1Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India
2Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore 570 005, India
Received 2 June 2003; revised 22 June 2003
showed antianaphylactic [2] and antiinflammatory
ABSTRACT: A simple high yielding method for the
activity [2,3]. Bakana et al. [4] isolated a ben-
integration of heterocyclic rings viz. 1,3,4-oxadiazole
zophenone analogue (garcinol) from the stem bark
and azetidin-2-one at the benzophenone nucleus
of Garcinia huillensis grown in Zaire and used in
has been developed starting from substituted 2-
central-African traditional medicine, and found this
hydroxybenzophenones, and by using mild condi-
to exhibit chemotherapeutical activity against gram-
tions, wet solid surface, and microwave irradiation.
positive and gram-negative cocci, mycobacteria, and
A comparison of this microwave-accelerated reaction
fungi [4]. 1,3,4-Oxadiazole is associated with po-
with conventional heating condition is also illus-
tent pharmacological activity due to the presence
ꢀ
C
trated. 2003 Wiley Periodicals, Inc. Heteroatom Chem
of toxophoric N C O linkage [5]. Considerable
evidence has been accumulated to demonstrate the
efficacy of 1,3,4-oxadiazole, including its use in her-
15:37–42, 2004; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10210
bicides, fungicides, hypnotics sedatives [6], as well
as its antibacterial [7], analgesic, antimalarial [8],
INTRODUCTION
antiinflammatory [9], hypoglycemic [10], anticon-
vulsant, diuretic, and antimitotic activity [11]. Be-
sides, considerable work has been carried out both
with regard to heterocylic chemistry and pharmaco-
logical activity, viz., antiviral, anesthetic, and anti-
convulsant activity of the azetidin-2-one ring system
[12,13]. Encouraged by these informations it was
considered valuable to integrate 1,3,4-oxadiazole-
azetidin-2-one moiety in benzophenone framework.
The microwaves enhance chemical reactions in
general [14,15] as well as on inorganic solid sup-
ports in particular [16,17], they have gained popular-
ity over the usual homogeneous and heterogeneous
reactions [18] as they can be carried out rapidly, and
provide pure products in quantitative yields without
the use of solvents. It was shown that solvent free
The efficiency of benzophenone derivatives as
chemotherapeutic agent is well established and their
chemistry has been extensively studied. In the past
years, the literature is enriched with progressive find-
ing about the synthesis and pharmacological ac-
tions of fused heterocycles. Literature survey re-
vealed that benzophenone derivatives are associated
with potent biological activity, such as, inhibition
of HIV-1 reverse transcriptase and the growth of
HIV-1 in MT-4 cells [1]. These compounds also
Correspondence to: S. Shashikanth; e-mail: skanth1@
rediffmail.com.
Contract grant sponsor: UGC, New Delhi.
2003 Wiley Periodicals, Inc.
c
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37

38 Khanum, Shashikanth, and Sudha
conditions are especially propitious to microwave
activation [19], as they provide an opportunity to
work with open vessels, thus avoiding the risk of
high pressure development and with a possibility
of carrying out the reaction on a preparative scale
in addition to the associated selectivity and ease
of manipulation [15,20]. To develop environmen-
tally benign solventless methods, using montmoril-
lonite K10 clay as solid support and microwave ac-
tivation, we report herein a solventless synthesis of
2-[3-chloro-4-(3-bromophenyl)azetidin-2-onyl] 5-(2-
benzoyl-phenoxymethyl) 1,3,4-oxadiazoles 6a–d.
On comparing the synthesis by microwave-
assisted method, with that by the conventional
method, we observed that the reaction progressed
very fast with excellent yield in the former. The re-
action remains incomplete in the absence of solid
support even after prolonged exposure to microwave
radiation. Among various mineral supports exam-
ined, such as alumina, montmorillonite K10 clay, sil-
ica gel, etc., clay was found to give the best results.
Hence the reactions carried out with microwave
technique are superior to the reactions using con-
ventional methods in our experiments. The time re-
quired for the progress of reactions and the yield of
compounds are as shown in Table 1.
RESULTS AND DISCUSSION
The synthetic route is depicted in Scheme 1. Con-
densation of substituted 2-hydroxybenzophenones
1a–d with ethyl chloroacetate yielded substituted
ethyl-2-benzoyl-phenoxy acetates 2a–d [21], which
on treatment with 80% hydrazine hydrate in ethanol
afforded the respective 2-benzoyl-phenoxy acethy-
drazides 3a–d. The cyclization of 3a–d with cyan-
ogen bromide furnished the corresponding 2-amino
5-(2-benzoyl-phenoxymethyl) 1,3,4-oxadiazoles 4a–
d [22]. Condensation of 4a–d with 3-bromo ben-
zaldehyde with a drop of glacial acetic acid fur-
nished Schiff bases, 2-(3-bromobenzylidene)amino
5-(2-benzoyl-phenoxymethyl) 1,3,4-oxadiazoles 5a–
d. The azetidin-2-one moiety in the compounds
5a–d was introduced by the cycloaddition of
chloroacetylchloride in the presence of triethylamine
to give 6a–d.
EXPERIMENTAL
Melting points were determined with Thomas
Hoover capillary melting point apparatus and are
uncorrected. IR spectra were recorded in Nujol on a
FT-IR Shimadzu 8300 spectrophotometer and NMR
spectra were recorded on a Bruker spectrophotome-
ter in CDCl3 solution. The H NMR and 13C NMR
1
spectra were measured at 300 and 90 MHz, respec-
tively. The chemical shifts are reported as parts per
million relative to internal TMS. Elemental analy-
sis results are within 0.4% of the calculated value.
Chemicals were purchased from Aldrich Chemical
Co. TLC was performed on preactivated (110◦C) sil-
ica gel plates using ethyl acetate:chloroform (7:2)
as eluent and the plates were visualized with UV
light.
SCHEME 1

Microwave-Assisted Synthesis of 2-Amino and 2-Azetidinonyl 5-(2-Benzoyl-phenoxymethyl) 1,3,4-Oxadiazoles 39
2b: mp 65–67◦C; IR (Nujol): 1672 (C O),
TABLE 1 Time Required (min) and Yield (%) of all Com-
pounds Prepared
1
1738 cm−1 (ester, C O); H NMR (CDCl3): δ 1.21 (t,
J = 7 Hz, 3H, CH3 of ester), 4.23 (q, J = 6 Hz, 2H, CH2
Thermal
Microwave
of ester), 4.5 (s, 2H, CH2), 7.2–7.75 (m, 8H, Ar H); 13
C
Time
Yield
Time
Yield
NMR (CDCl3): δ 13.62 (q), 59.52 (t), 75.61 (t), 115.2
(d), 124.8 (s), 125.8 (s), 128.22 (d), 130.1 (d), 131.5
(d), 132.21 (d), 133.6 (d), 137.8 (s), 161.7 (s), 171.8
(s), 187.03 (s). Anal. Calcd for C17H15ClO4 (318.5): C,
64.05; H, 4.70; Cl, 11.14%. Found: C, 64.02; H, 4.67;
Cl, 11.11%.
2a
2b
2c
2d
4a
4b
4c
4d
5a
5b
5c
5d
6a
6b
6c
6d
480
450
480
510
480
450
450
480
360
390
390
360
300
330
330
300
80
79
70
72
74
72
70
71
70
71
71
73
60
62
63
60
8
9
8
90
85
78
80
82
80
77
78
80
85
85
86
70
75
74
71
9
10
12
12
10
5
8
8
5
8
10
10
9
2c: mp 69–71◦C; IR (Nujol): 1672 (C O),
1
1736 cm−1 (ester, C O); H NMR (CDCl3): δ 1.2 (t,
J = 7 Hz, 3H, CH3 of ester), 4.22 (q, J = 6 Hz, 2H,
CH2 of ester), 4.45 (s, 2H, CH2), 7.22–7.8 (m, 8H,
Ar H); 13C NMR (CDCl3): δ 13.61 (q), 59.51 (t), 75.61
(t), 117.1 (d), 122.4 (s), 123.8 (d), 127.8 (s), 128.21
(d), 130.1 (d), 132.2 (d), 133.3 (d), 137.8 (s), 165.8
(s), 171.0 (s), 187.03 (s). Anal. Calcd for C17H15BrO4
(363): C, 56.19; H, 4.13; Br, 22.03%. Found: C, 56.17;
H, 4.10; Br, 22.0%.
2d: mp 58–60◦C; IR (Nujol): 1660 (C O),
1
1730 cm−1 (ester, C O); H NMR (CDCl3): δ 1.2 (t,
General Procedure for 2a–d
J = 7 Hz, 3H, CH3 of ester), 2.25 (s, 3H, CH3), 3.8 (s,
3H, OCH3), 4.2 (q, J = 6 Hz, 2H, CH2 of ester), 4.42 (s,
2H, CH2), 7.0–7.6 (m, 7H, Ar H); 13C NMR (CDCl3): δ
13.63 (q), 20.92 (q), 56.0 (q), 59.53 (t), 75.6 (t), 113.71
(d), 113.8 (d), 123.32 (s), 129.7 (s), 130.1 (s), 131.1 (d),
131.81 (d), 133.91 (d), 160.62 (s), 165.7 (s), 171.02 (s),
187.04 (s). Anal. Calcd for C19H20O5(328): C, 69.51; H,
6.09%. Found: C, 69.49; H, 6.05%.
Thermal Method. A mixture of 1a (5 g, 0.02 mol)
and ethyl chloroacetate (2.4 g, 0.02 mol) in dry ace-
tone (60 ml) and anhydrous potassium carbonate
(2.8 g, 0.02 mol) was refluxed for 8 h, then cooled,
and the solvent removed under reduced pressure.
The residual mass was triturated with ice water to re-
move potassium carbonate and extracted with ether
(3 × 50 ml). The ether layer was then washed with
10% sodium hydroxide solution (3 × 30 ml) followed
by water (3 × 30 ml) and then dried over anhydrous
sodium sulphate and evaporated to dryness to get
crude solid, which on recrystallization with ethanol
gave 2a. Yield 5.39 g (80%).
General Procedure for 3a–d
In a typical procedure, 80% hydrazine hydrate (0.3 g,
6 mmol) was added in drops to 2a (2 g, 6 mmol) in
methanol (10 ml), and stirred for 1 h at room tem-
perature. A white solid separated, which on recrys-
tallization with ethanol gave 3a. Yield 1.43 g (75%).
3a: mp 177–180◦C; IR (Nujol): 1620 (C O), 1655
(amide, C O), 3110–3215 cm−1 (NH NH2); 1H NMR
(CDCl3): δ 2.3 (s, 3H, CH3), 3.7 (bs, 2H, NH2), 4.5
(s, 2H, CH2), 7.1–7.6 (m, 7H, Ar H), 9.25 (bs, 1H,
CONH); 13C NMR (CDCl3): δ 20.91 (q), 78.0 (t), 113.7
(d), 123.3 (s), 128.21 (d), 129.62 (d), 129.7 (s), 130.5
(d), 131.8 (d), 132.6 (d), 133.51 (s), 133.9 (d), 139.2
(d), 160.6 (s), 170.3 (s), 187.0 (s). Anal. Calcd for
C16H15ClN2O3 (318.5): C, 60.28; H, 4.70; Cl, 11.14; N,
8.79%. Found: C, 60.24; H, 4.67; Cl, 11.10; N, 8.75%.
3b: mp 181–183◦C; IR (Nujol): 1630 (C O), 1668
(amide, C O), 3120–3223 cm−1 (NH NH2); 1H NMR
(CDCl3): δ 3.72 (bs, 2H, NH2), 4.55 (s, 2H, CH2), 7.15–
7.75 (m, 8H, Ar H), 9.35 (bs, 1H, CONH); 13C NMR
(CDCl3): δ 78.01 (t), 115.2 (d), 124.8 (s), 125.8 (s),
128.21 (d), 130.1 (d), 131.51 (d), 132.62 (d), 133.61
(d), 137.81 (s), 161.7 (s), 170.31 (s), 187.03 (s). Anal.
Microwave Irradiation Method. In a typical pro-
cedure, a mixture of 1a (1 g, 4 mmol) and ethyl
chloroacetate (0.48 g, 4 mmol) was thoroughly mixed
with clay (1:3 w/w) in the solid state, using a vortex
mixer, and subjected to microwave irradiation op-
erating at 40% power for 8 min. After conventional
work-up, this was followed by recrystallization with
ethanol. A white solid of 2a was obtained.
2a: mp 60–62◦C; IR (Nujol): 1670 (C O), 1735
1
cm−1 (ester, C O); H NMR (CDCl3): δ 1.2 (t, J =
7 Hz, 3H, CH3 of ester), 2.3 (s, 3H, CH3), 4.2 (q, J =
6 Hz, 2H, CH2 of ester), 4.45 (s, 2H, CH2), 7.2–7.6
(m, 7H, Ar H); 13C NMR (CDCl3): δ 13.6 (q), 20.9 (q),
59.5 (t), 75.6 (t), 113.7 (d), 123.3 (s), 128.2 (d), 129.61
(d), 129.7 (s), 130.5 (d), 131.8 (d), 132.6 (d), 133.5
(s), 139.2 (s), 133.9 (d), 160.6 (s), 171.0 (s), 187.0 (s),
Anal. Calcd for C18H17O4Cl (332.5): C, 64.96; H, 5.11;
Cl, 10.67%. Found: C, 64.94; H, 5.07; Cl, 10.64%.

40 Khanum, Shashikanth, and Sudha
1H NMR (CDCl3): δ 3.36 (bs, 2H, NH2), 5.12 (s, 2H,
CH2), 7.35–7.9 (m, 8H, Ar H); 13C NMR (CDCl3): δ
72.01 (t), 113.71 (d), 123.32 (s), 128.22 (d), 129.71
(s), 130.12 (d), 131.81 (d), 132.2 (d), 133.91 (d), 137.8
(s), 157.51 (s), 160.6 (s), 163.6 (s), 187.03 (s). Anal.
Calcd for C16H12ClN3O3 (329.5): C, 58.27; H, 3.64; Cl,
10.77; N, 12.74%. Found: C, 58.29; H, 3.62; Cl, 10.79;
N, 12.76%.
Calcd for C15H13ClN2O3(304.5): C, 59.11; H, 4.26; Cl,
11.65; N, 9.19%. Found: C, 59.12; H, 4.24; Cl, 11.67;
N, 9.17%.
3c: mp 182–185◦C; IR (Nujol): 1625 (C O), 1670
(amide, C O), 3115–3220 cm−1 (NH NH2); 1H NMR
(CDCl3): δ 3.72 (bs, 2H, NH2), 4.6 (s, 2H, CH2), 7.15–
7.76 (m, 8H, Ar H), 9.35 (bs, 1H, CONH); 13C NMR
(CDCl3): δ 78.01 (t), 117.1 (d), 122.4 (s), 123.8 (d),
127.8 (s), 128.2 (d), 130.1 (d), 132.2 (d), 133.3 (d),
137.8 (s), 165.8 (s), 170.3 (s), 187.03 (s). Anal. Calcd
for C15H13BrN2O3 (349): C, 51.57; H, 3.72; Br, 23.92;
N, 8.02%. Found: C, 51.54; H, 3.70; Br, 23.89; N, 8.0%.
3d: mp 175–177◦C; IR (Nujol): 1610 (C O), 1645
(amide, C O), 3100–3205 cm−1 (NH NH2); 1H NMR
(CDCl3): δ 2.2 (s, 3H, CH3), 3.5 (bs, 2H, NH2), 3.9 (s,
3H, OCH3), 4.55 (s, 2H, CH2), 7.2–7.9 (m, 7H, Ar H),
9.4 (bs, 1H, CONH); 13C NMR (CDCl3): δ 20.92 (q),
56.0 (q), 78.02 (t), 113.72 (d), 113.82 (d), 129.6 (d),
129.72 (s), 130.1 (s), 131.1 (d), 131.8 (d), 133.9 (d),
160.62 (s), 165.7 (s), 170.3 (s), 187.04 (s). Anal. Calcd
for C17H18N2O4 (314): C, 64.96; H, 5.73; N, 8.91%.
Found: C, 64.94; H, 5.70; N, 8.89%.
4c: mp 129–131◦C; IR (Nujol): 1175 (C O C
linkage), 1645 (C O), 1685 (C N), 3120 cm−1 (NH2);
1H NMR (CDCl3): δ 3.35 (bs, 2H, NH2), 5.11 (s, 2H,
CH2), 7.35–7.9 (m, 8H, Ar H); 13C NMR (CDCl3): δ
72.01 (t), 112.8 (d), 123.8 (d), 125.7 (s), 126.7 (s),
130.11 (d), 132.82 (d), 135.22 (d), 137.98 (s), 157.32
(s), 163.4 (s), 165.6 (s), 187.03 (s). Anal. Calcd for
C16H12BrN3O3 (374): C, 51.33; H, 3.20; Br, 21.39;
N, 11.22%. Found: C, 51.30; H, 3.22; Br, 21.37; N,
11.25%.
4d: mp 135–137◦C; IR (Nujol): 1180 (C O C
linkage), 1650 (C O), 1688 (C N), 3124 cm−1 (NH2);
1H NMR (CDCl3): δ 2.3 (s, 3H, CH3), 3.37 (bs, 2H,
NH2), 3.75 (s, 3H, OCH3), 5.2 (s, 2H, CH2), 7.37–7.95
(m, 7H, Ar H); 13C NMR (CDCl3): δ 20.92 (q), 56.0
(q), 72.02 (t), 113.72 (d), 113.8 (d), 123.31 (s), 129.72
(s), 130.1 (s), 131.1 (d), 131.82 (d), 133.9 (d), 157.6 (s),
160.61 (s), 163.8 (s), 165.7 (s), 187.04 (s). Anal. Calcd
for C18H17N3O4(339): C, 63.71; H, 5.01; N, 12.38%.
Found: C, 63.68; H, 5.04; N, 12.36%.
General Procedure for 4a–d
Thermal Method. A mixture of 3a (1.5 g,
4.7 mmol) and cyanogen bromide (0.73 g, 0.070 mol)
in ethanol (20 ml) was refluxed for 8 h. The cooled
reaction mixture was neutralized with sodium bicar-
bonate solution and poured onto crushed ice. The
solid product was isolated, and on recrystallization
with DMF gave 4a. Yield 0.39 g (74%).
General Procedure for 5a–d
Thermal Method. A mixture of 4a (0.5 g,
1.42 mmol), 3-bromo benzaldehyde (0.26 g, 1.42
mmol), and a drop of glacial acetic acid were re-
fluxed in methanol (30 ml) for about 6 h. The solvent
was distilled off at reduced pressure and the solid
mass thus obtained was recrystallized from a chlo-
roform:benzene mixture to afford 5a. Yield 0.364 g
(70%).
Microwave Irradiation Method. A mixture of 3a
(1.5 g, 4.7 mmol) and cyanogen bromide (0.73 g,
0.070 mol) was thoroughly mixed with clay (1:3 w/w)
in the solid state, using a vortex mixer. The mixture
was transferred into a tube and sealed (to prevent
gases affecting the inside of the oven). The tube was
subjected to microwave irradiation operating at 60%
power for 10 min, and after conventional work-up,
was followed by recrystallization with DMF. A white
solid of 4a was obtained.
Microwave Irradiation Method. A mixture of 4a
(0.5 g, 1.42 mmol), 3-bromo benzaldehyde (0.26 g,
1.42 mmol), and a drop of glacial acetic acid was
thoroughly mixed with clay (1:3 w/w) in the solid
state, using a vortex mixer, and subjected to mi-
crowave irradiation operating at 50% power for
5 min. After conventional work-up, this was followed
by recrystallization with DMF. A white solid of 5a
was obtained.
4a: mp 120–122◦C; IR (Nujol): 1160 (C O C
linkage), 1625 (C O), 1670 (C N), 3110 cm−1 (NH2);
1H NMR (CDCl3): 2.2 (s, 3H, CH3), 3.33 (bs, 2H, NH2),
5.0 (s, 2H, CH2), 7.3–7.9 (m, 7H, Ar H); 13C NMR
(CDCl3): δ 20.9 (q), 72.0 (t), 113.7 (d), 123.3 (s), 128.2
(d), 129.6 (d), 129.7 (s), 130.5 (d), 131.8 (d), 132.61
(d), 133.5 (s), 139.2 (s), 133.9 (d), 157.17 (s), 160.6
(s), 163.21 (s), 187.0 (s). Anal. Calcd for C17H14Cl
N3O3(343.5): C, 59.38; H, 4.07; Cl, 10.33; N, 12.22%.
Found: C, 59.36; H, 4.09; Cl, 10.30; N, 12.19%.
4b: mp 124–126◦C; IR (Nujol): 1170 (C O C
linkage), 1640 (C O), 1680 (C N), 3115 cm−1 (NH2);
5a: mp 150–152◦C; IR (Nujol): 1130 (C O C
linkage), 1580 ( N CH), 1600 (C N), 1665 cm−1
1
(C O); H NMR (CDCl3): δ 2.2 (s, 3H, CH3), 5.12 (s,
2H, CH2), 6.8–7.8 (m, 11H, Ar H), 8.1 (s, 1H, N CH);
13C NMR (CDCl3): δ 20.9 (q), 72.0 (t), 113.7 (d), 123.2
(s), 123.3 (s), 128.0 (d), 128.2 (d), 129.6 (d), 129.7 (s),

Microwave-Assisted Synthesis of 2-Amino and 2-Azetidinonyl 5-(2-Benzoyl-phenoxymethyl) 1,3,4-Oxadiazoles 41
130.5 (d), 130.8 (d), 131.8 (d), 132.3 (d), 132.6 (d),
Microwave Irradiation Method. To a stirred so-
lution of compound 5a (0.51 g, 1 mmol) and triethyl
amine (0.12 g, 1.2 mmol) in 1,4 dioxane (20 ml),
chloroacetylchloride (0.135 g, 1.2 mmol) was added
drop wise at 0–5◦C. The reaction mixture was stirred
for about 1 h and the precipitated amine hydrochlo-
ride was filtered off. From reaction mixture, solvent
was removed under reduced pressure and the solid
was thoroughly mixed with clay (1:3 w/w) in the solid
state, using a vortex mixer. Finally, it was subjected
to microwave irradiation operating at 50% power for
8 min. After conventional work-up, this was followed
by recrystallization with DMF. A white solid of 6a
was obtained.
133.41 (d), 133.5 (s), 133.91 (d), 134.1 (d), 139.2 (s),
157.20 (s), 160.6 (s), 163.26 (s), 163.7 (d), 187.0 (s).
Anal. Calcd for C24H17BrCl N3O3 (510.5): C, 56.47; H,
3.33; Br, 15.67; Cl, 6.95; N, 8.22%. Found: C, 56.45;
H, 3.35; Br, 15.69; Cl, 6.93; N, 8.24%.
5b: mp 157–159◦C; IR (Nujol): 1135 (C O C
linkage), 1590 ( N CH), 1610 (C N), 1670 cm−1
1
(C O); H NMR (CDCl3): δ 5.15 (s, 2H, CH2), 6.85–
7.85 (m, 12H, Ar H), 8.12 (s, 1H, N CH); 13C NMR
(CDCl3): δ 72.02 (t), 115.2 (d), 123.21 (s), 124.8 (s),
125.8 (s), 128.02 (d), 128.2 (d), 130.1 (d), 130.8 (d),
131.5 (d), 132.2 (d), 132.3 (d), 133.43 (s), 133.6 (d),
134.13 (d), 137.8 (s), 157.55 (s), 161.7 (s), 163.66
(s), 163.7 (d), 187.02 (s). Anal. Calcd for C23H15BrCl
N3O3 (496.5): C, 55.58; H, 3.02; Br, 16.11; Cl, 7.15; N,
8.45%. Found: C, 55.55; H, 3.05; Br, 16.14; Cl, 7.17;
N, 8.48%.
6a: mp 203–205◦C; IR (Nujol): 1135 (C O C
linkage), 1605 (C N), 1668 (C O), 1748 (ꢀ-lactam
C O); 1H NMR (CDCl3): δ 2.22 (s, 3H, CH3), 4.83 (d,
J = 7 Hz, 1H, N CH), 5.2 (s, 2H, CH2), 5.4 (d, J =
7 Hz, 1H, CHCl), 6.71–7.82 (m, 11H, Ar H); 13C NMR
(CDCl3): δ 20.9 (q), 62.0 (d), 62.1 (d), 72.0 (t), 113.7
(d), 122.9 (s), 123.3 (s), 126.11 (d), 128.21 (d), 129.6
(d), 129.7 (s), 129.8 (d), 130.4 (d), 130.5 (d), 131.8
(d), 132.6 (d), 133.5 (s), 133.9 (d), 139.2 (s), 144.8 (s),
157.22 (s), 160.6 (s), 161.4 (s), 163.29 (s), 187.0 (s).
Anal. Calcd for C26H18BrCl2 N3O4 (587): C, 53.15; H,
3.06; Br, 13.62; Cl, 12.09; N, 7.15%. Found: C, 53.17;
H, 3.04; Br, 13.65; Cl, 12.06; N, 7.12%.
5c: mp 160–162◦C; IR (Nujol): 1140 (C O C
linkage), 1586 ( N CH), 1605 (C N), 1668 cm−1
1
(C O); H NMR (CDCl3): δ 5.13 (s, 2H, CH2), 6.82–
7.85 (m, 12H, Ar H), 8.12 (s, 1H, N CH); 13C NMR
(CDCl3): δ 72.01 (t), 112.8 (d), 123.21 (s), 123.8
(d), 125.7 (s), 126.7 (s), 128.01 (d), 128.2 (d), 130.1
(d), 130.8 (d), 132.21 (d), 132.31 (d), 133.42 (s),
134.12 (d), 135.4 (d), 137.8 (s), 157.38 (s), 163.7
(d), 163.48 (s), 165.8 (s), 187.01 (s). Anal. Calcd for
C23H15Br2N3O3 (541): C, 51.01; H, 2.77; Br, 29.57;
N, 7.76%. Found: C, 51.04; H, 2.75; Br, 29.59; N,
7.74%.
6b: mp 209–211◦C; IR (Nujol): 1138 (C O C
linkage), 1612 (C N), 1672 (C O), 1750 (ꢀ-lactam
1
C O); H NMR (CDCl3): δ 4.86 (d, J = 7 Hz, 1H,
5d: mp 153–155◦C; IR (Nujol): 1142 (C O C
N CH), 5.21 (s, 2H, CH2), 5.41 (d, J = 7 Hz, 1H,
CHCl), 6.75–7.86 (m, 12H, Ar H); 13C NMR (CDCl3):
δ 62.01 (d), 62.11 (d), 72.02 (t), 115.2 (d), 122.91 (s),
124.8 (s), 125.81 (s), 126.12 (d), 128.21 (d), 129.81
(d), 130.1 (d), 130.4 (d), 130.5 (d), 131.5 (d), 132.2
(d), 133.6 (d), 137.8 (s), 144.61 (s), 157.58 (s), 161.41
(s), 161.7 (s), 163.69 (s), 187.01 (s). Anal. Calcd for
C25H16BrCl2 N3O4 (573): C, 52.35; H, 2.79; Br, 13.96;
Cl, 12.39; N, 7.32%. Found: C, 52.37; H, 2.77; Br,
13.94; Cl, 12.40; N, 7.35%.
linkage), 1588 ( N CH), 1612 (C N), 1672 cm−1
1
(C O); H NMR (CDCl3): δ 2.21 (s, 3H, CH3), 3.73
(s, 3H, OCH3), 5.21 (s, 2H, CH2), 6.85–7.86 (m, 11H,
Ar H), 8.13 (s, 1H, N CH); 13C NMR (CDCl3): δ
20.91 (q), 56.02 (q), 72.02 (t), 113.71 (d), 113.8 (d),
123.22 (s), 123.3 (s), 128.03 (d), 129.72 (s), 130.1 (s),
130.8 (d), 131.1 (d), 131.82 (d), 132.32 (d), 133.44
(s), 133.93 (d), 134.14 (d), 157.65 (s), 160.62 (s),
163.7 (d), 163.84 (s), 165.7 (s), 187.04 (s). Anal. Calcd
for C25H20BrN3O4(506): C, 59.28; H, 3.95; Br, 15.81;
N, 8.3%. Found: C, 59.26; H, 3.92; Br, 15.83; N,
8.32%.
6c: mp 212–214◦C; IR (Nujol): 1144 (C O C
linkage), 1608 (C N), 1670 (C O), 1748 (ꢀ-lactam
1
C O); H NMR (CDCl3): δ 4.88 (d, J = 7 Hz, 1H,
N CH), 5.21 (s, 2H, CH2), 5.41 (d, J = 7 Hz, 1H,
CHCl), 6.72–7.86 (m, 12H, Ar H); 13C NMR (CDCl3):
δ 62.01 (d), 62.11 (d), 72.01 (t), 112.8 (d), 122.91
(s), 123.8 (d), 125.7 (s), 126.12 (d), 126.7 (s), 128.23
(d), 129.8 (d), 130.1 (d), 130.4 (d), 130.5 (d), 132.2
(d), 135.4 (d), 137.8 (s), 144.8 (s), 157.4 (s), 161.4
(s), 163.6 (s), 165.8 (s), 187.02 (s). Anal. Calcd for
C25H16Br2ClN3O4 (617.5): C, 48.58; H, 2.59; Br, 25.91;
Cl, 5.74; N, 6.80%. Found: C, 48.56; H, 2.57; Br, 25.93;
Cl, 5.77; N, 6.83%.
General Procedure for 6a–d
Thermal Method. To a stirred solution of com-
pound 5a (0.51 g, 1 mmol) and triethylamine (0.12 g,
1.2 mmol) in 1,4 dioxane (10 ml), chloroacetylchlo-
ride (0.135 g, 1.2 mmol) was added drop wise at 0–
5◦C. The reaction mixture was stirred for about 1 h
and the precipitated amine hydrochloride was fil-
tered off. The filtrate was refluxed for about 5 h and
the separated solid was crystallized from methanol
to give 6a. Yield 0.35 g (60%).
6d: mp 217–219◦C; IR (Nujol): 1145 (C O C
linkage), 1610 (C N), 1675 (C O), 1752 (ꢀ-lactam

42 Khanum, Shashikanth, and Sudha
C O); 1H NMR (CDCl3): δ 2.23 (s, 3H, CH3), 3.73 (s,
3H, OCH3), 4.9 (d, J = 7 Hz, 1H, N CH), 5.22 (s,
2H, CH2), 5.42 (d, J = 7 Hz, 1H, CHCl), 6.8–7.88 (m,
11H, Ar H); 13C NMR (CDCl3): δ 20.92 (q), 56.01 (q),
62.02 (d), 62.12 (d), 72.03 (t), 113.7 (d), 113.8 (d),
122.92 (s), 123.33 (s), 126.13 (d), 129.7 (s), 129.8 (d),
130.1 (s), 130.4 (d), 130.5 (d), 131.1 (d), 131.82 (d),
133.93 (d), 144.6 (s), 157.41 (s), 160.63 (s), 161.42
(s), 163.66 (s), 165.7 (s), 187.04 (s). Anal. Calcd for
C27H21BrClN3O5 (582.5): C, 55.62; H, 3.60; Br, 13.73;
Cl, 6.09; N, 7.21%. Found: C, 55.60; H, 3.62; Br, 13.72;
Cl, 6.07; N, 7.19%.
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In conclusion, we have developed a highly ef-
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benzoyl-phenoxymethyl) 1,3,4-oxadiazoles and their
azetidin-2-one derivatives, that occurs remarkably
fast, under mild conditions, using inexpensive
reagents, and a household microwave oven as the
irradiation source. The eco-friendly advantages
of these solvent-free protocols can be found in
instances where catalytic amounts of supported
agents are used, since they provide reduction of
solvents, thus preventing pollution “at source.”
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methods may be ascribed to nonthermal effects.
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ACKNOWLEDGMENTS
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The authors express sincere gratitude to University
of Mysore, Mysore for the laboratory facilities pro-
vided to us.