Ultrasound assisted one pot synthesis, spectral, antimicrobial and antioxidant studies of novel 4-[1-oxo-3-(substituted phenyl)-2-propenyl]-3-substituted phenyl sydnones

Article abstract of DOI:10.14233/ajchem.2015.18864

4-[1-Oxo-3-(substituted aryl)-2-propenyl]-3-substituted phenyl sydnones (2a-i, 3a-i, 4a-i) are synthesized by ultrasonication method. The synthesis was carried out by reaction of 4-acetyl-3-(substituted phenyl)sydnones (1a-i) with various substituted aryl

Full text of DOI:10.14233/ajchem.2015.18864

Asian Journal of Chemistry; Vol. 27, No. 8 (2015), 3063-3068
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.18864
Ultrasound Assisted One Pot Synthesis, Spectral, Antimicrobial and Antioxidant
Studies of Novel 4-[1-Oxo-3-(substituted phenyl)-2-propenyl]-3-substituted Phenyl Sydnones
1,*
2
3
SACHIN K. BHOSALE , SHREENIVAS R. DESHPANDE and RAJENDRA D. WAGH
1Department of Pharmaceutical Chemistry, S.M.B.T. College of Pharmacy, Nandi Hills, Dhamangaon-422 403, India
2Department of Medicinal and Pharmaceutical Chemistry, HSK College of Pharmacy, BVVS Campus, Bagalkote-587 101, India
3Department of Pharmaceutical Chemistry, A.R.A. College of Pharmacy, Nagaon, Dhule-424 005, India
*Corresponding author: Fax: +91 2553 202001; E-mail: sachiniper@rediffmail.com
Received: 19 November 2014;
Accepted: 13 December 2014;
Published online: 27 April 2015;
AJC-17193
4-[1-Oxo-3-(substituted aryl)-2-propenyl]-3-substituted phenyl sydnones (2a-i, 3a-i, 4a-i) are synthesized by ultrasonication method.
The synthesis was carried out by reaction of 4-acetyl-3-(substituted phenyl)sydnones (1a-i) with various substituted aryl aldehydes
(Ar-CHO). The structures of compounds were established by using NMR, IR, MS and elemental analysis. Compounds were evaluated for
antibacterial, antifungal and antioxidant activity. Some of the synthesized compounds have shown good to moderate activity against gram
negative bacteria whereas compounds 3c, 4c and 4f have shown marked activity against fungal strains. The compounds 2c, 3c, 4f have
shown potent antioxidant activity as compared to reference standards. The compound 4f (IC50 = 3.17 µM) is the most potent with methyl
group as substituent showing good antioxidant activity even at very low concentrations. The ultrasonic method of synthesis was found to
be simple, reduces reaction time and gives good yield when compared with traditional methods of synthesis.
Keywords: 1,2,3-Oxadiazol-5-olate, Ultrasonication, Chalcones.
antioxidant activity of a new series of 4-[1-oxo-3-(substituted
aryl)-2-propenyl]-3-(substituted phenyl)sydnones.
INTRODUCTION
Sydnones form a subclass of mesoionic compounds belong
to the category of mesomeric betaines. The characteristics of
five membered heterocyclic ring of mesoionic compounds have
encouraged study of the chemical, physical and biological
properties of sydnones, as well as their potential applications.
Sydnones are mesoionic compounds containing the 1,2,3-
oxadiazole skeleton with an oxygen atom attached to the fifth
position1. A large number of sydnone derivatives have been
synthesized with biological interest and are reported to possess
a wide spectrum of biological and pharmacological activities
like antioxidant2-4, anticancer5,6 antihypertensive and anti-
anginous7, diuretic8, antimicrobial9-13, antitubercular14, analgesic,
antiinflammatory and antiarthritic15-18. Nowadays, the ultra-
sonic irradiation technique is becoming motivating, as this
technique not only decreases reaction times, but also improves
yield in a large variety of polyfunctionalized heterocycles.
Compared with traditional methods, this method is more conve-
nient and easily controlled19-21. In continuation to our interest
in the chemical and pharmacological properties of sydnone
derivatives, and as sonochemistry is attracting considerable
research activity within the synthetic chemistry22, we report
herein the ultrasonic promoted synthesis and antimicrobial/
EXPERIMENTAL
The starting material 4-acetyl-3-(4-chlorophenyl)sydnone
(i), 4-acetyl-3-(4-fluorophenyl)sydnone (ii) and 4-acetyl-3-(3-
chloro-4-fluorophenyl)sydnone (iii) were synthesized accor-
ding to the standard procedure. Compounds 2a-i, 3a-i, 4a-i
were synthesized under sonication conditions in ethanol by
cooling the mixture of 4-acetyl-3-(substituted phenyl)sydnone
(i, ii, iii), sodium hydroxide aqueous solution at 5-10 °C and to
this, various substituted aryl aldehydes were added under ultra-
sonication conditions for 15-20 min. The precipitate obtained
was filtered, washed with cold water and recrystallized from
ethanol and ethyl acetate (1:1) to get the title compounds
(Scheme-I, Table-1). The structures of all the newly synthe-
sized compounds were confirmed by elemental analysis in
addition to the IR, 1H NMR, 13C NMR and mass spectral data.
All melting points (uncorrected) were determined using
a Systonic digital melting/boiling point apparatus. Infrared
spectra were recorded in KBr discs using Jasco FTIR 1460
Plus spectrometer. NMR spectra were obtained on a BRUKER
AVANCE II 400 NMR spectrometer at 500 MHz for 1H and

3064 Bhosale et al.
Asian J. Chem.
F
MASS (LC-MS) instrument. Elemental analysis (C, H, N) were
corresponding to the proposed structures within 0.4 % of
the theoretical values. The ultrasonic irradiation was performed
by using a Biotechnics India TM ultrasonic cleaner bath, model
1510,AC input 115V, output 50W, 1.9 liters with a mechanical
timer (60 min with continuous hold) and heater switch, 47
KHz. The bacterial strains (Staphylococcus aureus, Bacillus
subtilis, Escherichia coli, Pseudomonas aeuroginosa), Candida
albicans and Aspergillus niger were obtained from the national
collection of industrial micro-organisms (NCIM), branch of
national chemical laboratory (NCL) Pune, India. Ampicillin
trihydrate, clotrimazole, DPPH, propyl gallate, 2-tert-butyl-
4-hydroxyanisole were obtained from Sigma-Aldrich,
Mumbai, India.
O
N+
Ar
O-
N
O
i
2a-i
O
Ar
O
Cl
F
ii
O-
N+
Ar
H
O
3a-iN
1a-i
iii
O
Cl
N+
Ar
Synthesis of 4-[1-oxo-3-(substituted aryl)-2-propenyl]-
3-(substituted) sydnones (2a-g, 3a-g 4a-g): 4-[1-oxo-3-(4-
N,N-dimethylaminophenyl)-2-propenyl]-3-(3-chloro-4-
fluorophenyl)sydnone (4f):A mixture of 4-acetyl-3-(3-chloro-
4-fluorophenyl)sydnone (iii) (2.6 g, 0.01 mol), aq. NaOH
and ethanol (95 %, 20 mL) was cooled at (5-10 °C). 4-N,N-
dimethylaminobenzaldehyde (2 g, 0.012 mol) was added to
this solution under ultra-sonication conditions and allowed to
react for 20 min. The precipitate obtained was filtered, washed
with cold water and recrystallized from ethanol (95 %) and
ethyl acetate (1:1) to give the title compound (86 %). Other
compounds were synthesized in same manner using respective
aryl aldehydes (Scheme-I).
O-
N
O
4a-i
F
Cl
Cl
F
O
O
O
i =
ii=
iii=
N+
N+
N+
O-
H3CO
H3CO
H3CO
N
O-
O-
N
N
O
O
O
c=
d=
b=
Cl
e=
O2N
Ar, a=
f=
O
NO2
HO
g=
N
h=
i=
H3CO
N
OH
Scheme-I: Synthesis of compounds 2a-i, 3a-i, 4a-i
Spectral data of synthesized compound
125 MHz for 13C, the chemical shifts are expressed in δ (ppm)
downfield from tetramethylsilane (TMS). Electron impact
mass spectra were recorded on WATERS, Q-TOF MICRO-
4-[1-Oxo-3-(phenyl)-2-propenyl]-3-(4-chlorophenyl)-
sydnone (2a): IR (KBr, νmax, cm-1): 1753 (C=O, sydnone),
1662 (C=O, styryl ketone); 1H NMR δ 6.83 (d, 1H, J = 15.57,
TABLE-1
PHYSICO-CHEMICAL DATA OF COMPOUNDS 2a-i, 3a-i, 4a-i
Compound
Ar
m.f.
m.w.
Yield (%)
m.p. (°C)
2a
2b
2c
2d
2e
2f
2g
2h
2i
3a
3b
3c
3d
3e
3f
3g
3h
3i
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
2-Furyl
4-ClC6H4
3,4,5-(OCH3)3C6H2
4-NO2C6H4
4-N(CH3)2C6H4
2-NO2C6H4
3-OCH3, 4-OHC6H3
2-OH-3-quinolinyl
C6H5
2-Furyl
4-ClC6H4
3,4,5-(OCH3)3C6H2
4-NO2C6H4
4-N(CH3)2C6H4
2-NO2C6H4
3-OCH3, 4-OHC6H3
2-OH-3-quinolinyl
C6H5
2-Furyl
4-ClC6H4
C17H11N2O3Cl
C15H9N2O4Cl
C17H10N2O3Cl2
C20H17N2O6Cl
C17H10N3O5Cl
C19H16N3O3Cl
C17H10N3O5Cl
C18H13N2O5Cl
C20H12N3O4Cl
C17H11N2O3F
C15H9N2O4F
C17H10N2O3ClF
C20H17N2O6F
C17H10N3O5F
C19H16N3O3F
C17H10N3O5F
C18H13N2O5F
C20H12N3O4F
C17H10N2O3ClF
C15H8N2O4ClF
C17H9N2O3Cl2F
C20H16N2O6ClF
C17H9N3O5ClF
C19H15N3O3ClF
C17H9N3O5ClF
C18H12N2O5ClF
C20H11N3O4ClF
326.74
316.70
361.18
416.81
371.74
369.74
271.74
372.74
393.78
310.28
300.24
344.72
400.36
355.35
353.28
355.28
356.31
377.33
344.72
344.72
379.20
434.72
389.72
387.72
389.72
390.72
411.77
83
87
85
80
81
92
83
79
82
92
78
89
82
84
90
92
95
88
86
81
93
95
87
86
85
79
91
139-141
118-120
112-114
109-111
117-119
100-102
112-114
135-137
189-191
135-137
120-122
115-117
106-108
109-111
112-114
96-98
128-130
194-196
150-152
132-134
133-135
120-122
136-138
110-112
106-108
157-159
205-207
3,4,5-(OCH3)3C6H2
4-NO2C6H4
4-N(CH3)2C6H4
2-NO2C6H4
3-OCH3, 4-OHC6H3
2-OH-3-quinolinyl

Vol. 27, No. 8 (2015)
Studies of Novel 4-[1-Oxo-3-(substituted phenyl)-2-propenyl]-3-substituted Phenyl Sydnones 3065
olefinic αH), 7.82 (d, 1H, J = 15.57, olefinic βH), 7.97, 7.97,
7.97, 7.97 (FC6H4-), 7.45, 7.45, 7.43, 7.43, 7.709 (C6H5-); 13C
NMR δ 116.88, 116.88, 124.57, 124.57, 127.33, 127.33,
128.74, 128.74, 128.05, 128.92, 134.71,136.19, 143.25,
144.45, 168.4, 168.3, 171.3; MS m/z 326.63 (M+).
4-[1-Oxo-3-(2-furyl)-2-propenyl]-3-(4-chlorophenyl)-
sydnone (2b): IR (KBr, νmax, cm-1): 1765 (C=O, sydnone),
1676 (C=O, styryl ketone); 1H NMR δ 6.92 (d, 1H, J = 15.76,
olefinic αH), 7.03 (t, 1H, J = 15.76, furyl-4H), 7.26-7.42 (m,
2H, ArH), 7.73-7.96 (m, 3H, ArH, furyl-3H and olefinic βH),
8.25 (d, 1H, J = 7.05, furyl-5H); 13C NMR δ 143.25, 154.03,
136.19, 111.36, 129.05, 131.02, 104.83, 124.57, 124.57,
127.28, 142.28, 116.88, 116.88, 129.58, 171.3168.3, 126.08,
126.08, 144.45, 141.39; MS m/z 316.46 (M+).
4-[1-Oxo-3-(4-cholrophenyl)-2-propenyl]-3-(4-chloro-
phenyl)sydnone (2c): IR (KBr, νmax, cm-1): 1763 (C=O,
sydnone), 1671 (C=O, styryl ketone); 1H NMR δ 6.81 (d, 1H,
J = 15.52, olefinic αH), 7.28-7.43 (m, 2H, ArH), 7.6 (d, 2H,
J = 15.26, ArH), 7.73-7.82 (m, 4H, ArH and olefinic βH); 13C
NMR δ 116.88, 116.88, 124.57, 124.57, 129.05, 129.19,
129.19, 129.54, 129.54, 133.75, 135.68, 136.19, 143.25,
144.45, 168.3, 168.4, 171.3; MS m/z 361.18 (M+).
4-[1-Oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-3-
(4-chlorophenyl)sydnone (2d): IR (KBr, νmax, cm-1): 1752
(C=O, sydnone), 1657 (C=O, styryl ketone); 1H NMR δ 3.93
(s, 9H, OCH3), 6.82 (d, 1H, J = 16.52, olefinic αH), 6.87 (s,
2H, ArH), 7.21-7.38 (m, 2H, ArH), 7.81 (t, 2H, J = 16.52,
ArH and olefinic βH); 13C NMR δ 56.16, 56.16, 60.90, 111.03,
116.88, 116.88, 124.57, 124.57, 127.05, 127.16, 129.05,
131.02, 136.19, 139.05, 139.75 143.25, 143.60, 144.45,
152.88, 168.3, 168.4, 171.3; MS m/z 416.53 (M+).
4-[1-Oxo-3-(4-nitrophenyl)-2-propenyl]-3-(4-chloro-
phenyl)sydnone (2e): IR (KBr, νmax, cm-1): 1755 (C=O, sydnone),
1667 (C=O, styryl ketone); 1H NMR δ 7.38 (d, 1H, J = 16.56,
olefinic αH), 7.42-7.56 (m, 2H,ArH), 7.76 (m, 1H,ArH), 7.93
(d, 1H, J = 16.56, olefinic βH), 8.69 (d, 2H, J = 5.78, ArH),
8.93 (d, 2H, J = 5.78, ArH); 13C NMR δ 116.88, 116.88,
117.29, 117.29, 123.17, 124.57, 124.57, 129.05, 129.10,
129.10, 136.19, 140.47, 143.25, 144.45, 168.4, 168.4, 171.3;
MS m/z 371.49 (M+).
4-[1-Oxo-3-(4-N,N-dimethylaminophenyl)-2-propenyl]-
3-(4-chlorophenyl)sydnone (2f): IR (KBr, νmax, cm-1): 1755
(C=O, sydnone), 1660 (C=O, styryl ketone); 1H NMR δ 3.08
(s, 6H, N(CH3)2), 6.74-6.77 (m, 3H, ArH and olefinic αH),
7.36-7.49 (m, 2H, ArH), 7.78-7.83 (m, 4H, ArH and olefinic
βH); 13C NMR δ 40.30, 40.30, 113, 113, 116.88, 116.88,
124.57, 124.57, 127.05, 127.05, 127.05, 127.16, 127.86,
129.05, 131.02, 133.98, 133.98, 136.19, 142.68, 143.25,
143.25, 144.45, 151.43, 168.3, 168.4, 171.3; MS m/z 369.59 (M+).
4-[1-Oxo-3-(2-nitrophenyl)-2-propenyl]-3-(4-chloro-
phenyl)sydnone (2g): IR (KBr, νmax, cm-1): 1759 (C=O, sydnone),
1662 (C=O, styryl ketone); 1H NMR δ 6.98 (d, 1H, J = 16.56,
olefinic δH), 7.32-7.48 (m, 2H,ArH), 7.78-8.21 (m, 4H,ArH),
8.30-8.33 (m, 2H, ArH and olefinic βH); 13C NMR δ 116.88,
116.88, 121.77, 122.2, 124.57, 124.57, 127.6, 128.55, 129.39,
129.5, 133.41, 136.19, 143.23, 148.37, 168.3, 168.4, 171.3;
MS m/z 271.52 (M+).
1662 (C=O, styryl ketone); 1H NMR δ 6.818 (d, 1H, J = 15.57,
olefinic αH), 7.816 (d, 1H, J = 15.57, olefinic βH), 7.57, 7.95,
7.85 (FClC6H3-), 7.45, 7.45, 7.43, 7.43, 7.64 (C6H5-); 13C NMR
δ 126.88, 126.88, 124.57, 124.57, 127.33, 127.33, 128.74,
128.74, 128.05, 128.92, 134.71, 136.19, 141.39, 143.25,
144.45, 168.3, 171.3; MS m/z 310.63 (M+).
4-[1-Oxo-3-(2-furyl)-2-propenyl]-3-(4-fluorophenyl)-
sydnone (3b): IR (KBr, νmax, cm-1): 1765 (C=O, sydnone),
1676 (C=O, styryl ketone); 1H NMR δ 6.92 (d, 1H, J = 16.85,
olefinic αH), 7.03 (t, 1H, J = 16.76, furyl-4H), 7.26-7.42 (m,
2H, ArH), 7.73-7.96 (m, 3H, ArH, furyl-3H and olefinic βH),
8.25 (d, 1H, J = 15.11, furyl-5H); 13C NMR δ 143.25, 154.03,
136.19, 111.36, 129.05, 131.02, 104.83, 124.57, 124.57,
127.28, 142.28, 126.77, 116.88, 129.58, 171.3168.3, 126.08,
126.08, 144.45, 141.39; MS m/z 300.46 (M+).
4-[1-Oxo-3-(4-cholrophenyl)-2-propenyl]-3-(4-fluoro-
phenyl)sydnone (3c): IR (KBr, νmax, cm-1): 1763 (C=O,
sydnone), 1671 (C=O, styryl ketone); 1H NMR δ 6.81 (d, 1H,
J = 10.73, olefinic αH), 7.28-7.43 (m, 2H, ArH), 7.6 (d, 2H,
J = 5.35, ArH), 7.73-7.82 (m, 4H, ArH and olefinic βH); 13C
NMR δ 126.77, 126.77, 124.57, 124.57, 129.05, 129.19,
129.19, 129.54, 129.54, 133.75, 135.68, 136.19, 143.25,
144.45, 168.3, 141.39, 171.3; MS m/z 344.18 (M+).
4-[1-Oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-3-
(4-fluorophenyl)sydnone (3d): IR (KBr, νmax, cm-1): 1752
(C=O, sydnone), 1657 (C=O, styryl ketone); 1H NMR δ 3.93
(s, 9H, OCH3), 6.82 (d, 1H, J = 10.52, olefinic αH), 6.87 (s,
2H, ArH), 7.21-7.38 (m, 2H, ArH), 7.81 (t, 2H, J = 10.49,
ArH and olefinic βH); 13C NMR δ 56.16, 56.16, 60.90, 111.03,
126.88, 122.66, 124.57, 124.57, 127.05, 127.16, 129.05,
131.02, 136.19, 139.05, 139.75 143.25, 143.60, 144.45,
152.88, 168.3, 141.4, 171.3; MS m/z 400.53 (M+).
4-[1-Oxo-3-(4-nitrophenyl)-2-propenyl]-3-(4-fluoro-
phenyl)sydnone (3e): IR (KBr, νmax, cm-1): 1755 (C=O,
sydnone), 1667 (C=O, styryl ketone); 1H NMR δ 7.38 (d, 1H,
J = 16.23, olefinic αH), 7.42-7.56 (m, 2H, ArH), 7.76 (m, 1H,
ArH), 7.93 (d, 1H, J = 16.56, olefinic βH), 8.69 (d, 2H, J =
5.65, ArH), 8.87 (d, 2H, J = 5.78, ArH); 13C NMR δ 117.29,
117.29, 123.17, 124.57, 124.57, 126.77, 126.77, 129.05, 129.10,
129.10, 136.19, 140.47, 141.39, 143.25, 144.45, 168.4, 171.3;
MS m/z 355.49 (M+).
4-[1-Oxo-3-(4-N,N-dimethylaminophenyl)-2-pro-
penyl]-3-(4-fluorophenyl)sydnone (3f): IR (KBr, νmax, cm-1):
1755 (C=O, sydnone), 1660 (C=O, styryl ketone); 1H NMR δ
3.08 (s, 6H, N(CH3)2), 6.74-6.77 (m, 3H, ArH and olefinic
αH), 7.36-7.49 (m, 2H, ArH), 7.78-7.83 (m, 4H, ArH and
olefinic βH); 13C NMR δ 40.30, 40.30, 113, 113, 126.77,
126.77, 124.57, 124.57, 127.05, 127.05, 127.05, 127.16,
127.86, 129.05, 131.02, 133.98, 133.98, 136.19, 142.68,
143.25, 143.25, 144.45, 151.43, 168.3, 141.39, 171.3 ; MS
m/z 353.59 (M+).
4-[1-Oxo-3-(2-nitrophenyl)-2-propenyl]-3-(4-fluoro-
phenyl)sydnone (3g): IR (KBr, νmax, cm-1): 1759 (C=O,
sydnone), 1662 (C=O, styryl ketone); 1H NMR δ 6.98 (d, 1H,
J = 16.49, olefinic αH), 7.32-7.48 (m, 2H, ArH), 7.78-8.21
13
(m, 4H, ArH), 8.30-8.33 (m, 2H, ArH and olefinic βH); C
NMR δ 126, 126, 121.77, 122.2, 124.57, 124.57, 127.6,
128.55, 129.39, 129.5, 133.41, 136.19, 143.23, 148.37, 168.3,
141.4, 171.3; MS m/z 358.52 (M+).
4-[1-Oxo-3-(phenyl)-2-propenyl]-3-(4-fluorophenyl)-
sydnone (3a): IR (KBr, νmax, cm-1): 1753 (C=O, sydnone),

3066 Bhosale et al.
Asian J. Chem.
4-[1-Oxo-3-(phenyl)-2-propenyl]-3-(3-chloro-4-fluoro-
phenyl)sydnone (4a): IR (KBr, νmax, cm-1): 1753 (C=O,
sydnone), 1662 (C=O, styryl ketone); 1H NMR δ 6.81 (d, 1H,
J = 16.36, olefinic αH), 7.83 (d, 1H, J = 16.36, olefinic βH),
7.59, 7.59, 7.97, 7.97, 7.50 (FC6H4-), 7.45, 7.45, 7.43, 7.43,
7.64, 7.709 (C6H5-); 13C NMR δ 117.23, 122.66, 124.57,
125.16, 127.33, 127.33, 128.74, 128.74, 128.05, 128.92,
134.71, 136.19, 143.25, 144.45, 162, 168.3, 171.3; MS m/z
344.63 (M+).
NMR δ 116.88, 122.66, 121.77, 122.2, 124.57, 124.57, 127.6,
128.55, 129.39, 129.5, 133.41, 136.19, 143.23, 148.37, 168.3,
162, 171.3; MS m/z 389.52 (M+).
General procedure for synthesis of 4-[1-oxo-3-(substi-
tuted aryl)-2-propenyl]-3-(substitutedphenyl)sydnones (2h,
2i, 3h, 3i, 4h, 4i).
4-[1-Oxo-3-(4-hydroxy-3-methoxyphenyl)-2-propenyl]-
3-(3-chloro-4-fluorophenyl)sydnone (4h): Dry hydrogen
chloride gas was passed through the suspension of compound
iii (2.6 g, 0.01 mol) and vanillin (1.8 g, 0.012 mol) in 20 mL
ethanol (95 %), for 0.5 h under cooling (5-10 °C). The reaction
mixture was left overnight at room temperature and poured
into cold water. The separated precipitate was filtered, washed,
dried in air and re-crystallised from ethanol (95 %) to give 4 h
(79.10 %): Other compounds were synthesized similarly using
respective aryl aldehydes.
4-[1-Oxo-3-(4-hydroxy-3-methoxyphenyl)-2-propenyl]-
3-(4-chlorophenyl)sydnone (2h): IR (KBr, νmax, cm-1): 1758
(C=O, sydnone), 1660 (C=O, styryl ketone); 1H NMR δ 3.97
(s, 3H, OCH3), 5.98 (s, br, 1H, OH), 6.79-6.88 (m, 2H, ArH
and olefinic αH), 7.32-7.68 (m, 4H, Ar-H), 7.76-7.78 (m, 2H,
ArH and olefinic βH); 13C NMR δ 55.93, 105.73, 112.08,
117.32, 120.96, 121.48, 123.31, 125.83, 128.36, 131.89,
136.15, 146.10, 148.63, 149.76, 159.38, 166.48, 188.56; MS
m/z 272 (M+).
4-[1-Oxo-3-(2-furyl)-2-propenyl]-3-(3-chloro-4-fluoro-
phenyl)sydnone (4b): IR (KBr, νmax, cm-1): 1765 (C=O,
sydnone), 1676 (C=O, styryl ketone); 1H NMR δ 6.92 (d, 1H,
J = 16.54, olefinic αH), 7.03 (t, 1H, J = 16.73, furyl-4H),
7.26-7.42 (m, 2H, ArH), 7.73-7.96 (m, 3H, ArH, furyl-3H,
and olefinic βH), 8.25 (d, 1H, J = 7.05, furyl-5H); 13C NMR δ
143.25, 154.03, 136.19, 111.36, 129.05, 131.02, 104.83,
124.57, 124.57, 127.28, 142.28, 117.23, 122.66, 129.58,
171.3168.3, 126.08, 126.08, 144.45, 162; MS m/z 334.46 (M+).
4-[1-Oxo-3-(4-cholrophenyl)-2-propenyl]-3-(3-chloro-
4-fluorophenyl)sydnone (4c): IR (KBr, νmax, cm-1): 1763
(C=O, sydnone), 1671(C=O, styryl ketone); 1H NMR δ 6.81
(d, 1H, J = 15.69, olefinic αH), 7.28-7.43 (m, 2H, ArH), 7.6
(d, 2H, J = 15.45, ArH), 7.73-7.82 (m, 4H, ArH and olefinic
βH); 13C NMR δ 117.23, 116.88, 124.57, 124.57, 129.05,
129.19, 129.19, 129.54, 129.54, 133.75, 135.68, 136.19,
143.25, 144.45, 168.3, 162, 171.3; MS m/z 379.18 (M+).
4-[1-Oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-3-
(3-chloro-4-fluorophenyl)sydnone (4d): IR (KBr, νmax, cm-1)
1752 (C=O, sydnone), 1657 (C=O, styryl ketone); 1H NMR δ
3.93 (s, 9H, OCH3), 6.82 (d, 1H, J = 15.66, olefinic αH), 6.87
(s, 2H, ArH), 7.21-7.38 (m, 2H, ArH), 7.81 (t, 2H, J = 15.53,
ArH and olefinic βH); 13C NMR δ 56.16, 56.16, 60.90, 111.03,
127.23, 122.66, 124.57, 124.57, 127.05, 127.16, 129.05, 131.02,
136.19, 139.05, 139.75 143.25, 143.60, 144.45, 152.88, 168.3,
162, 171.3; MS m/z 434.53 (M+).
4-[1-Oxo-3-(2-hydroxy-3-quinolinyl)-2-propenyl]-3-
(4-chlorophenyl)sydnone (2i): IR (KBr, νmax, cm-1): 1757
(C=O, sydnone), 1672 (C=O, styryl ketone); 1H NMR δ 6.76
(d, 1H, J = 16.29, olefinic αH) 7.27-7.39 (m, 2H, ArH), 7.57-
7.8 (m, 2H, ArH and olefinic βH), 7.81-8.14 (m, 4H ArH),
8.42 (s, 1H, ArH), 11.47 (s, br, 1H, OH); 13C NMR δ 106.18,
117.61, 121.13, 122.24, 124.30, 125.26, 125.60, 127.31,
127.86, 128.63, 130.75, 131.89, 136.12, 136.65, 145.74,
146.58, 159.38, 166.37, 174.92, 187.64; MS m/z 393.48 (M+).
4-[1-Oxo-3-(4-hydroxy-3-methoxy phenyl)-2-propenyl]-
3-(4-fluorophenyl)sydnone (3h): m.p. 128-130 °C; IR (KBr,
4-[1-Oxo-3-(4-nitrophenyl)-2-propenyl]-3-(3-chloro-4-
fluorophenyl)sydnone (4e): IR (KBr, νmax, cm-1) 1755 (C=O,
sydnone), 1667 (C=O, styryl ketone); 1H NMR δ 7.38 (d, 1H,
J = 16.49, olefinic αH), 7.42-7.56 (m, 2H, ArH), 7.76 (m, 1H,
ArH), 7.93 (d, 1H, J = 16.42, olefinic βH), 8.69 (d, 2H, J =
5.66, ArH), 8.93 (d, 2H, J = 5.72, ArH); 13C NMR δ 117.23,
117.29, 117.29, 122.66, 123.17, 124.57, 125.16, 129.05,
129.10, 129.10, 136.19, 140.47, 143.25, 144.45, 168.4, 162,
171.3; MS m/z 389.49 (M+).
ν
max, cm-1) 1758 (C=O, sydnone), 1660 (C=O, styryl ketone);
1H NMR δ 3.97 (s, 3H, OCH3), 5.98 (s, br, 1H, OH), 6.79-
6.88 (m, 2H, ArH and olefinic αH), 7.32-7.68 (m, 4H, Ar-H),
13
7.76-7.78 (m, 2H, ArH and olefinic βH); C NMR δ 55.93,
105.73, 112.08, 117.32, 120.96, 121.48, 123.31, 125.83,
128.36, 131.89, 136.15, 146.10, 148.63, 149.76, 159.38,
166.48, 188.56; MS m/z 356.50 (M+).
4-[1-Oxo-3-(2-hydroxy-3-quinolinyl)-2-propenyl]-3-
(4-fluorophenyl)sydnone (3i): IR (KBr, νmax, cm-1): 1757
(C=O, sydnone), 1672 (C=O, styryl ketone); 1H NMR δ 6.76
(d, 1H, J = 16.30, olefinic αH) 7.27-7.39 (m, 2H, ArH), 7.57-
7.8 (m, 2H, ArH and olefinic βH), 7.81-8.14 (m, 4H ArH),
8.42 (s, 1H, ArH), 11.47 (s, br, 1H, OH); 13C NMR δ 106.18,
117.61, 121.13, 122.24, 124.30, 125.26, 125.60, 127.31,
127.86, 128.63, 130.75, 131.89, 136.12, 136.65, 145.74,
146.58, 159.38, 166.37, 174.92, 187.64; MS m/z 377.48 (M+).
4-[1-Oxo-3-(4-hydroxy-3-methoxy phenyl)-2-propenyl]-
3-(3-chloro-4-fluorophenyl)sydnone (4h): m.p. 157-159 °C;
IR (KBr, νmax, cm-1) 1758 (C=O, sydnone), 1660 (C=O, styryl
ketone); 1H NMR δ 3.97 (s, 3H, OCH3), 5.98 (s, br, 1H, OH),
6.79-6.88 (m, 2H, ArH and olefinic αH), 7.32-7.68 (m, 4H,
Ar-H), 7.76-7.78 (m, 2H, ArH and olefinic βH); 13C NMR δ
55.93, 105.73, 112.08, 117.32, 120.96, 121.48, 123.31, 125.83,
4-[1-Oxo-3-(4-N,N-dimethylaminophenyl)-2-
propenyl]-3-(3-chloro-4-fluoro phenyl)sydnone (4f): m.p.
110-112 °C; IR (KBr, νmax, cm-1) 1755 (C=O, sydnone), 1660
(C=O, styryl ketone); 1H NMR δ 3.08 (s, 6H, N(CH3)2), 6.74-
6.77 (m, 3H, ArH and olefinic αH), 7.36-7.49 (m, 2H, ArH),
13
7.78-7.83 (m, 4H, ArH and olefinic βH); C NMR δ 40.30,
40.30, 113, 113, 117.23, 122.86, 124.57, 125.16, 127.05,
127.05, 127.05, 127.16, 127.86, 129.05, 131.02, 133.98,
133.98, 136.19, 142.68, 143.25, 143.25, 144.45, 151.43, 168.3,
162, 171.3; MS m/z 387.59 (M+).
4-[1-Oxo-3-(2-nitrophenyl)-2-propenyl]-3-(3-chloro-4-
fluorophenyl)sydnone (4g): IR (KBr, νmax, cm-1) 1759 (C=O,
sydnone), 1662 (C=O, styryl ketone); 1H NMR δ 6.98 (d, 1H,
J = 16.56, olefinic αH), 7.32-7.48 (m, 2H, ArH), 7.78-8.21
13
(m, 4H, ArH), 8.30-8.33 (m, 2H, ArH and olefinic βH); C

Vol. 27, No. 8 (2015)
Studies of Novel 4-[1-Oxo-3-(substituted phenyl)-2-propenyl]-3-substituted Phenyl Sydnones 3067
128.36, 131.89, 136.15, 146.10, 148.63, 149.76, 159.38,
166.48, 188.56; MS m/z 390.50 (M+).
assay involved the reaction of the test compounds with 1,1-
diphenyl-2-picrylhydrazyl (DPPH) free radical. The reaction
was decrease in absorbance and it was measured at 515 nm
using micro plate reader (India). The radical scavenging activity
(%) was determined for the sample using DMSO treated
control group in comparison. The following equation was used
for calculation of radical scavenging activity.
4-[1-Oxo-3-(2-hydroxy-3-quinolinyl)-2-propenyl]-3-
(3-chloro-4-fluorophenyl)sydnone (4i): IR (KBr, νmax, cm-1)
1757 (C=O, sydnone), 1672 (C=O, styryl ketone); 1H NMR δ
6.76 (d, 1H, J = 16.35, olefinic αH) 7.27-7.39 (m, 2H, ArH),
7.57-7.8 (m, 2H,ArH and olefinic βH), 7.81-8.14 (m, 4HArH),
8.42 (s, 1H, ArH), 11.47 (s, br, 1H, OH); 13C NMR δ 106.18,
117.61, 121.13, 122.24, 124.30, 125.26, 125.60, 127.31,
127.86, 128.63, 130.75, 131.89, 136.12, 136.65, 145.74,
146.58, 159.38, 166.37, 174.92, 187.64; MS m/z 411.48 (M+).
in-vitro Antimicrobial activity: The synthesized com-
pounds were tested for their in vitro antimicrobial activity
against a panel of standard strains of the Gram-positive bacteria
(Staphylococcus aureusATCC NO 25923 and Bacillus subtilis
ATCC NO 6051), the Gram-negative bacteria (Escherichia coli
ATCC NO 25922 and Pseudomonas aeuroginosa ATCC NO
9721) and the yeast-like pathogenic fungus, Candida albicans
ATCC NO 2091 and Aspergillus niger ATCC NO 10594. The
primary screening was carried out using the agar disc-diffusion
method using Mullere Hinton agar medium and further MIC
was determined.
OD test well
OD control




Radicalscavengingactivity (%) = 100 −
×100


RESULTS AND DISCUSSION
The ultrasound assisted synthesized compounds were
identified by spectral data and evaluated for their antimicrobial
and antioxidant activity. Compound 4-[1-oxo-3-(2-furyl)-2-
propenyl]-3-(4-fluorophenyl)sydnone (3b), 4-[1-oxo-3-(2-
furyl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)sydnone (4b)
and 4-[1-oxo-3-(2-hydroxy-3-quinolinyl)-2-propenyl]-3-(3-
chloro-4-fluorophenyl)sydnone (4i) were found to possess
good antibacterial activity whereas 4-[1-oxo-3-(4-cholrophe-
nyl)-2-propenyl]-3-(4-fluorophenyl)sydnone (3c), 4-[1-oxo-
3-(4-cholrophenyl)-2-propenyl]-3-(3-chloro-4-fluorophenyl)-
sydnone (4c) and 4-[1-oxo-3-(4-N,N-dimethylaminophenyl)-
2-propenyl]-3-(3-chloro-4-fluoro phenyl)sydnone (4f) were
found to possess good antifungal activity. Compounds showed
Antioxidant assay: The free radical scavenging capacity
of the compound was measured by 1,1-diphenyl-2-picrylhy-
drazyl (DPPH) methods described by Chaudhary et al.23. The
TABLE-2
ANTIMICROBIAL ACTIVITIES AND MINIMUM INHIBITORY CONCENTRATION (MIC, µg/mL) OF
4-[1-OXO-3-(SUBSTITUTEDARYL)-2-PROPENYL]-3-SUBSTITUTED PHENYL SYDNONES
Diameter of growth inhibition zone (mm)
Minimum inhibitory concentration (MIC, µg/mL)
Compound
Compound
SA
BS
EC
PA
CA
AN
SA
BS
EC
PA
CA
AN
2a
2b
2c
2d
2e
2f
2g
2h
2i
3a
3b
3c
3d
3e
3f
3g
3h
3i
4a
4b
4c
4d
4e
4f
-
-
12
11
14
12
10
10
-
10
13
11
14
12
12
-
09
15
12
14
13
12
-
-
15
-
15
13
14
13
12
-
-
-
17
14
-
17
11
17
-
-
-
16
14
-
16
12
14
-
2b
2c
2d
2f
2h
2i
3b
3c
3d
3f
3h
3i
4b
4c
4d
4e
8
ND
8
ND
ND
8
8
ND
8
ND
ND
16
8
16
8
8
ND
4
ND
ND
8
4
ND
8
ND
ND
8
4
8
8
8
8
8
ND
4
0.5
ND
8
ND
8
ND
ND
8
4
ND
4
ND
ND
8
8
16
4
8
ND
8
ND
ND
4
4
ND
8
ND
ND
8
4
8
8
16
8
8
ND
4
ND
8
8
ND
8
8
13
10
14
11
11
09
-
8
8
16
ND
ND
4
8
8
16
ND
ND
4
8
ND
4
16
ND
ND
8
8
8
16
ND
ND
4
8
ND
4
-
13
-
13
-
14
10
14
12
15
13
12
-
-
-
-
-
14
11
13
12
10
-
14
12
13
12
11
-
-
13
-
14
13
13
12
12
-
18
17
-
14
12
12
-
17
17
-
13
12
13
-
8
8
8
ND
8
16
8
8
ND
4
2
-
-
-
4f
4g
4h
13
10
14
11
14
13
13
10
10
14
19
NT
14
11
14
12
15
12
13
-
14
12
15
13
13
12
12
-
ND
8
ND
ND
2
ND
8
ND
ND
2
-
-
-
-
4i
18
17
-
17
13
17
-
17
16
-
17
12
14
-
Ampicillin
Clotrimazole
1
ND
2
ND
ND
4g
4h
4i
-
-
-
14
18
NT
15
16
NT
15
15
NT
Ampicillin
Clotrimazole
NT
21
NT
20
Inactive (inhibition zone < 9 mm). NT: not tested; ND = not detected;
The broad spectrum antibacterial drug ampicillin and the antifungal drug clotrimazole against Staphylococcus aureus ATCC NO 25923 (SA),
Bacillus subtilis ATCC NO 6051 (BS), Escherichia coli ATCC NO 25922 (EC), Pseudomonas aeuroginosa ATCC NO 9721 (PA), Candida
albicans ATCC NO 2091 (CA) and Aspergillus niger ATCC NO 10594 (AN)

3068 Bhosale et al.
Asian J. Chem.
significant to moderate activity for in vitro antimicrobial
activity (Table-2). This report proposed its potential application
as a lead compounds for designing and development of potent
antimicrobial agent. In general, the antibacterial activity to be
dependent on the nature of substituents rather than basic
skeleton of the molecules. Within the 1,2,3-oxadiazol-5-olate
series 2a-i, 3a-i, 4a-i, it was noticed that the substituents at
both position 3-substituted phenyl and 4-substituted aryl have
great influence on the antifungal activity, the highest antifungal
activity was observed with the 4-substituted aryl, 4-ClC6H4
(2c, 3c, 4c), 3,4,5-(OCH3)3C6H2 (2d, 3d, 4d), 4-N(CH3)2C6H4
(2f, 3f, 4f) and 3-OCH3, 4-OHC6H3 (4h). Similarly the substi-
tuents at both position 3-substituted phenyl and 4-substituted
aryl also have great influence on the antibacterial activity, the
highest antibacterial activity was observed with the 4-substi-
tuted aryl,2-furyl (2b, 3b, 4b), 3,4,5-(OCH3)3C6H2 (2d, 3d,
4d), 2-OH-3-quinolinyl (2i, 3i, 4i) and 4-NO2C6H4 (4e). In
series, it seems that the presence of 4-Cl (in series 2), 4-F (in
series 3), 4-F, 3-Cl (in series 4) at 3-substituted phenyl along
with only electron donating functional groups at 4-substituted
aryl (such as 3,4,5-(OCH3)3C6H2, 4-N(CH3)2C6H4, 3-OCH3, 4-
OHC6H3 might be responsible for highest antifungal activity,
while both electron donating groups (such as -OCH3, -OH)
and electron withdrawing groups (such as -Cl, -NO2) might
be responsible for highest antibacterial activity. Compounds
2b, 2c, 2f, 3b, 3c, 3f, 3b, 4b, 4c, 4f showed good antioxidant
activity with IC50 values 5.18, 4.18, 5.12, 6.18, 4.26, 4.15,
5.32, 3.34 and 3.172 µM, respectively compared with reference
standards Propyl gallate and 2-tert-butyl-4-hydroxyanisol
(Table-3). Some of the tested compounds (2c, 3c and 4f) are
found to be more potent antioxidants as compared to reference
standards. The compound 4f (IC50 = 3.17 µM) was the most
potent compound with methyl group as substituent showing
good antioxidant activity even at very low concentrations.
The results proved the necessity for further investigations to
design molecules such as cyclization of sydnones with phenyl
hydrazine, hydrazine and hydroxylamine for development of
imminent potent antimicrobial, antioxidant and antitumor
molecules.
ACKNOWLEDGEMENTS
The authors acknowledge SAIF Punjab University,
Chandigarh (India) for spectral analysis. The authors also
extend thanks to Dr. A.S. Dhake and S.M.B.T. COP,
Dhamangaon, India for providing necessary facilities to carry
out the research work.
TABLE-3
ULTRASOUND IRRADIATED SYNTHESIZED
4-[1-OXO-3-(SUBSTITUTED ARYL)-2-PROPENYL]-3-
SUBSTITUTED PHENYL) SYDNONES UNDER AMBIENT
CONDITIONS (5-10 °C), TIME REQUIRED FOR SYNTHESIS
AND THEIR ANTIOXIDANT ACTIVITY
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Compd.
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8.23 2.43
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24.11 0.18
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9.23 1.78
5.32 0.27
3.34 0.56
29.7 1.06
12.09 1.02
03.17 0.42
13.04 0.32
21.34 0.41
11.12 0.45
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4-NO2C6H4
4-N(CH3)2C6H4
2-NO2C6H4
3-OCH3, 4-OHC6H3
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