Transformation of the sydnone ring into oxadiazolinones. A convenient one-pot synthesis of 3-aryl-5-methyl-1,3,4-oxadiazolin-2-ones from 3- arylsydnones and their antimicrobial activity

Article abstract of DOI:10.1016/S0014-827X(99)00103-2

3-Arylsydnones (Ia-u) have been converted into the corresponding 3-aryl- 5-methyl-1,3,4-oxadiazolin-2-ones (IIIa-u) by a single-step reaction with bromine in acetic anhydride. In the preliminary screening of all these compounds, the halogen-substituted de

Full text of DOI:10.1016/S0014-827X(99)00103-2

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Il Farmaco 55 (2000) 65–67
New Compounds
Transformation of the sydnone ring into oxadiazolinones.
A convenient one-pot synthesis of 3-aryl-5-methyl-1,3,4-
oxadiazolin-2-ones from 3-arylsydnones and their antimicrobial
activity
Shanta G. Mallur, Bharati V. Badami *
Post-Graduate Department of Studies in Chemistry, Karnatak Uni6ersity, Dharwad 580 003, India
Received 5 April 1998; accepted 9 August 1999
Abstract
3-Arylsydnones (Ia–u) have been converted into the corresponding 3-aryl-5-methyl-1,3,4-oxadiazolin-2-ones (IIIa–u) by a
single-step reaction with bromine in acetic anhydride. In the preliminary screening of all these compounds, the halogen-substituted
derivatives have shown antimicrobial activities equal to those of the standard drugs used. © 2000 Elsevier Science S.A. All rights
reserved.
Keywords: Sydnone ring; Oxadiazolinones; Antimicrobial activity
1. Introduction
bazic acid ethylester [4] and 1-phenyl-2-acetylphenyl-
hydrazine [5]. The latter method gave the isomeric
1,2,4-triazolidin-3,5-diones and 1,2,4-triazolidin-5-ones
also resulting from the formation of oxadiazolin-2-ones
in only 35% yield. (Scheme 1). Instead, the one-pot
synthesis of these compounds from sydnones is
achieved in 80% yield without the formation of any
isomers. Hence, sydnones can be used as versatile start-
ing materials for the preparation of such heterocycles,
which are accessible with difficulty. The mechanism of
this conversion has been explained in terms of 1,3-dipo-
lar cycloaddition of an acid anhydride to the intermedi-
ate product 3-aryl-4-bromosydnone (II) [1] (Scheme 2).
In this paper we now present the synthesis of the new
oxadiazolinones IIIa–u and their antimicrobial activity.
The title compounds were prepared from 3-arylsyd-
nones by the reaction of bromine in acetic anhydride.
The initial step at 0°C gave the 3-aryl-4-bromosydnones
IIa–u which were then converted in situ into the oxadi-
azolinones IIIa–u by heating the solution at 60°C. The
3-arylsydnones Ia–u and their 4-bromo derivatives
IIa–u were prepared by literature methods [6,7].
Sydnones are one of the few heterocycles which have
gained importance as synthones, as they readily un-
dergo ring transformation to various heterocycles by
1,3-dipolar cycloaddition [1]. Such one-step conversions
of sydnones into pyrazole derivatives have been re-
ported from this laboratory [2,3].
2. Chemistry
In continuation of this work, in the present investiga-
tion we focused our attention on the synthesis of 3-aryl-
5-methyl-1,3,4-oxadiazolin-2-ones
3-arylsydnones (Ia–u). The aim of this work came from
the observation that such oxadiazolinones were synthe-
sised with difficulty starting from 3-acetyl-2-phenylcar-
(IIIa–u)
from
* Corresponding author.
E-mail address: unicard@renback.delhi.nic.in (B.V. Badami)
0014-827X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0014-827X(99)00103-2

66
S.G. Mallur, B.V. Badami / Il Farmaco 55 (2000) 65–67
Scheme 1.
3. Spectral characterisation
IIIc (meta substituted):
One singlet (1H, Ar)
and one multiplet (3H,
Ar) at l 7.20–7.60 ppm
Two doublets (2H each,
Ar, AA1 BB1) at l
7.20–7.70 ppm (J 8
Hz).
One multiplet (4H, Ar)
at l 7.20–7.80 ppm.
One singlet (1H, Ar) at
l 7.15 and two
The IR spectra of these compounds showed bands at
1775 cm−1 w(CꢀO) and 1630 cm−1 w(CꢀN). The ab-
sence of a band at 3100 cm−1, which is characteristic of
the sydnone ring carbonyl group, confirms the transfor-
mation. 1H NMR spectra of all these compounds
showed a singlet at l 2.40 ppm for the CH3 protons.
The protons on the aromatic ring appeared as given
below.
IIIb, e, g, i, j, m, o and p
(para substituted):
IIId, f, k, l and n (ortho
substituted):
IIIq, r, s, t and u
(disubstituted):
doublets (2H, Ar) at l
7.20 and 7.70 ppm.
IIIa:
One multiplet (5H Ar)
at l 7.20–7.60 ppm.
Scheme 2.

S.G. Mallur, B.V. Badami / Il Farmaco 55 (2000) 65–67
67
Table 1
5. Experimental
3-Aryl-5-methyl-1,3,4-oxadiazolin-2-ones
TLC was carried out on silica gel plates using a
benzene–ethanol mixture as eluent. The IR spectra
were recorded on an IR Nicolet-Impact-410, FTIR
spectrometer. 1H NMR spectra were recorded on a
Varian EM, 300 MHz, NMR Spectrometer in DMSO-
d6 with TMS as internal standard. The observed ele-
mental analysis results are within 0.4% of the
theoretical values.
Comp.
R
R1
Yield (%)
M.p. (°C)
a
b
c
e
f
g
h
i
j
k
l
m
n
o
p
q
r
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
82
80
84
80
75
80
82
85
72
70
75
88
85
86
90
85
80
70
80
74
95–96
82–83
138–39
121–22
139–40
98–99
96–97
111–12
86–87
5.1. Preparation of 3-aryl-5-methyl-1,3,4-oxadiazolin-
2-ones. IIa–u (general procedure)
4-CH3
3-CH3
2-CH3
2-OCH3
4-Cl
3-Arylsydnone (1.0 g) was suspended in acetic anhy-
dride (5 ml) at 0°C and an ice-cooled solution of
bromine (0.5 ml) in acetic anhydride (5 ml) was added
with stirring and cooling. 4-Bromosydnone separates
after the addition. The reaction mixture was then
heated on a water bath, gradually increasing the tem-
perature to 50–60°C for about 30 min. Vigorous evolu-
tion of CO2 was observed. The solution was then
diluted with water. The solid obtained was filtered,
washed with water and crystallised from ethanol (Table
1).
3-Cl
4-Br
4-NO2
2-NO2
2-COOH
4-COCH3
2-COCH3
4-COOCH3
4-COOCH2H
4-CH3
5-CH3
4-Cl
80–81
92–93
138–39
122–23
110–11
107–108
103–04
114–15
83–84
3-CH3
2-CH3
2-OCH3
4-CH3
4-Cl
s
t
u
3-Cl
3-F
92–93
101–02
Acknowledgements
4. Biological evaluation (antimicrobial activity)
The authors are grateful to Dr G.S. Puranik, former
Chairman, Department of Chemistry, Karnatak Uni-
versity, Dharwad, for valuable suggestions and
encouragement.
All these compounds were screened for their antimi-
crobial activity against two pathogenic bacteria, viz.,
Escherichia coli and Pseudomonas pyocyanous and two
cultures viz., Aspergillis niger and Rhizoctonia batati-
cola. The standard drugs used were Norfloxacin and
Griseofulvin. The tests were carried out by the cup–
plate method with 20 mg of the substance in 0.1 ml of
dimethylformamide. Dimethylformamide was used as
solvent control. The zone of inhibition was measured in
mm and was compared with that of the standard drugs.
From these qualitative studies it has been observed that
the halogen-substituted derivatives exhibit considerable
activity. The chloro compounds IIIg and h show
growth inhibition only against P. pyocyanous equal to
that of Norfloxacin while the bromo derivative IIIi
shows growth inhibition equal to the standard only
against E. coli. The antifungal activity of these com-
pounds is more than the standard against both strains.
Amongst the bihalogenated derivatives only chloro-
fluoro-substituted compound IIIu causes growth inhibi-
tion equal to the standard against both strains.
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