Synthesis and Antimicrobial Activity of (Z)-3-{[3-Oxobenzofuran-2(3H)-ylidene]methyl}-4H-chromen-4-one Derivatives

Article abstract of DOI:10.1134/S1070363218030283

A series of (Z)-3-{[3-oxobenzofuran-2(3H)-ylidene]methyl}-4H-chromen-4-one derivatives have been synthesized from 2-hydroxyl acetophenones by the Vilesmeier–Haack reaction, Claisen–Schmidt reaction and mercury(II) acetate/cupric bromide. All the synthesized compounds were characterized by IR, ¹H and ¹³C NMR, and mass spectral data and elemental analysis. The products were tested for their in vitro antimicrobial activity.

Full text of DOI:10.1134/S1070363218030283

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 3, pp. 566–572. © Pleiades Publishing, Ltd., 2018.
Synthesis and Antimicrobial Activity
of (Z)-3-{[3-Oxobenzofuran-2(3H)-ylidene]methyl}-
1
4
H-chromen-4-one Derivatives
a
b
a
c
b
S. Pervaram , D. Ashok *, C. V. R. Reddy , M. Sarasija , and B. A Rao
a
Department of Chemistry, Jawaharlal Nehru Technological University, Hyderabad, Telangana, 500085 India
b
Green and Medicinal Chemistry Laboratory, Department of Chemistry,
Osmania University, Hyderabad, Telangana, 500007 India
*
e-mail: Sridhar.pervaram@gmail.com
c
Department of Chemistry, Satavahana University, Karimnagar, Telangana, 505001 India
Received November 9, 2017
Abstract—A series of (Z)-3-{[3-oxobenzofuran-2(3H)-ylidene]methyl}-4H-chromen-4-one derivatives have
been synthesized from 2-hydroxyl acetophenones by the Vilesmeier–Haack reaction, Claisen–Schmidt reaction
1
13
and mercury(II) acetate/cupric bromide. All the synthesized compounds were characterized by IR, H and
C
NMR, and mass spectral data and elemental analysis. The products were tested for their in vitro antimicrobial
activity.
Keywords: aurones, chromanones, benzofurans, Vilesmeier–Haack reaction, Claisen–Schmidt reaction, mercury(II)
acetate–cupric bromide, antimicrobial activity
DOI: 10.1134/S1070363218030283
INTRODUCTION
in the current study (Z)-3-{[3-oxobenzofuran-2(3H)-
ylidene]methyl}-4H-chromen-4-one derivatives were
synthesised from the respective chalcones (Scheme 1).
Aurones [(Z)-2-benzylidenebenzofuran-3-(2H)-ones]
constitute a less studied subclass of flavonoids, that
rarely occur in nature. Aurones are responsible for
pigmentation of flowers, especially bright yellow
color, and fruits. Aurones and their synthetic analogues
were determined to be promising bioactive compounds
with anticancer [1, 2], antimicrobial [3], antioxidants
RESULTS AND DISCUSSION
Compounds 2a–2d were synthesized from substi-
tuted-2-hydroxy acetophenones 1a–1d by using the
Vilsmeier Haack reagent (POCl and DMF) at room
3
temperature. Compounds 3a–3g were synthesized by
condensation of 4-oxo-4H-chromene-3-carbaldehydes
[
4, 5], enzyme inhibitory [6, 7], and enzyme-inducing
activity [8].
2
a–2d with substituted-2-hydroxy acetophenones in
the presence of TEA and ethanol under microwave
irradiation and conventional heating methods. In case
of microwave irradiation, optimum results were
achieved by irradiating at 160 Watts for 4–5 min with
Chromanones (4H-benzopyran-4-one) are widely
spread in nature, compounds that demonstrate anti-
cancer [9], antifungal [10, 11], antioxidant [12], and
anti-HIV [13] activities. The compounds previously
synthesized by direct coupling of benzofuranones with
chromanones were associated with long reactions times,
tedious work up procedures and low yields. Recently
the microwave assisted organic synthesis became the
promising alternative to conventional methods as
effective, safe, economical, and eco-friendly [14]. In
view of the potential bioactivity and improvement of
synthetic methods for chromanone substituted aurones,
3
0 s intervals (Table 1). Chalcones 3a–3g reaction
with Hg(II) acetate in pyridine or CuBr in DMSO
2
gave 3-[(Z)-[3-oxobenzofuran-2(3H)-ylidene]methyl}-
4
H-chromen-4-ones 4a–4g. The processes that
involved CuBr in DMSO gave lower yields than Hg(II)
2
acetate in pyridine (Table 2).
Biological activity. Antimicrobial activity. Antimic-
robial activity of compounds 4a–4g has been assayed
within concentration range of 1 to 100 µg/mL against
gram positive and gram negative clinically important
1
The text was submitted by the authors in English.
5
66

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
567
Scheme 1. Synthesis of 3-{(Z)-[3-oxobenzofuran-2(3H)ylidene]methyl}-4H-chromen-4-ones (4a–4g).
O
OH
OH
POCl and DMF
3
+
ο
H
−
5 C to room temperature
CH3
CH3
R1
R
R
O
O
O
O
1
a−1d
2a−2d
TEA,MWI
or
EtOH, reflux
Hg(OAC) in pyridine
2
O
O
O
HO
R
or
O
CuBr in DMSO
2
R1
R1
R
O
O
O
4
a−4g
3a−3g
pathogens. Primarily, the Muller–Hinton agar method
was used. The tests indicated antibacterial activity
against all tested bacteria for compounds 4a, 4c, 4e,
and 4f.
The minimum inhibitory concentration (MIC, μg/mL)
of synthesized compounds 4a–4g was determined to be
much lower than that of Ciprofloxacin and Gentamicin
(Table 3).
Table 1. Physical data for (E)-3-[3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]-4H-chromen-4-one (3a–3g)
Conventional heating
Microwave irradiation
I
Compound no.
R
R
mp, °C
time, h
3.0
yield, %
68
time, min
yield, %
80
3
3
a
H
H
179–181
182–184
198–200
220–222
233–235
212–214
229–231
4
4
5
5
5
5
5
b
Me
Me
Br
Br
Cl
H
3.0
70
83
3
c
Me
H
3.2
70
83
3
d
2.8
69
83
3
e
Br
H
3.0
65
80
3
f
3.5
70
85
3
g
Cl
Cl
3.0
70
84
Table 2. Physical data for 3-{(Z)-[3-oxobenzofuran-2(3H)-ylidene]methyl}-4H-chromen-4-ones (4a–4g)
Yield, %
I
Compound no.
R
R
mp, °C
Hg(OAc)
2
in pyridine CuBr
2
in DMSO
4
a
H
H
222
85
80
78
82
80
79
77
74
78
70
72
78
77
70
4
b
Me
Me
Br
Br
Cl
H
226
4
c
Me
H
227–229
274–276
284–286
264–268
277–279
4
d
4
e
Br
H
4
f
4
g
Cl
Cl
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018

5
68
PERVARAM et al.
Table 3. Minimum inhibitory activity of the products
MIC value, µg/mL
Compound
Escherichia
coli
Klebsiella
Pseudomonas
aeruginosa
Staphylococcus
aureus
Streptococcus
pyogenes
pneumoniae
17.5±0.98
11.5±0.66
4
4
4
4
4
4
4
a
b
c
d
e
f
10.5±0.02
19.5±0.13
6.5±0.44
2.5±0.97
18.5±0.53
1.5±0.65
13.5±0.28
12.5±0.66
a
a
a
a
12.5±1.32
7.5±0.32
0.5±0.76
0.5±0.62
11.5±0.92
10.5±0.53
a
a
a
a
7.5±1.08
4.5±0.43
4.0±0.78
9.5±0.55
a
a
11.5±0.76
12.5±0.65
11.5±2.45
10.5±1.65
10.0±2.45
4.5±1.34
2.5±0.98
10.5±0.22
12.5±0.86
10.5±0.11
10.5±0.41
11.5±0.2.43
17.5±0.43
8.12±0.75
6.5±0.31
16.5±0.83
a
a
a
g
8.5±2.22
7.5±0.54
10.5±0.59
Ciprofloxacin
Gentamicin
8.2±4.08
1.5±1.08
8.08±0.79
2.5±0.43
9.5±0.11
6.5±0.48
a
Indicates statistically significant compared with Ciprofloxacin and Gentamicin (p ≤ 0.05).
Table 4. Minimum inhibitory concentration of synthesized compounds
Zone of inhibition, mm
MIC value, µg/mL
Compound
Concentration, µg/mL
Aspergillus niger Aspergillus flavus Aspergillus niger Aspergillus flavus
4
4
4
4
5
4
4
a
b
c
d
e
f
10
10
10
10
10
10
10
50
12.22±1.23
14.15±0.54
16.30±0.03
8.50±0.42
15.45±0.05
9.50±0.21
14.25±0.42
17.0±0.48
1.45±0.53
11.28±0.88
14.75±0.55
10.15±0.73
12.40±0.52
10.95±0.18
11.98±0.89
15.20±0.28
8.50±0.26
10.0±0.67
a
6.50±0.97
4.50±0.63
10.50±0.88
a
a
5.50±0.44
9.59±0.35
8.5.0±0.62
8.50±0.72
9.0±0.81
a
a
a
a
9.50±0.43
a
5.0±0.83
6.50±0.62
5.5±0.78
a
a
g
Nystatin
5.50±0.18
7.80±0.67
a
Indicates statistically significant compared with Nystatin (p ≤ 0.05).
1
Antifungal activity. Zones of inhibition for com-
pounds 4a–4g were assayed in vitro at concentration of
1
1
6
2
8
4
0
2
1
0 μg/mL against Aspergillus niger and Aspergillus
flavus (see figure). According to the accumulated data
the compounds 4b, 4c, 4e, and 4g exhibited high
activity against both organisms in comparison with the
antibiotic Nystatin.
Minimum inhibitory activity of fungal stain. The
compounds 4c, 4e, 4f, and 4g demonstrated the potent
inhibitory activity at low concentrations against
Aspergillus niger and Aspergillus flavus (Table 4),
whereas the compounds 4a, 4b and 4d did not show
any antifungal activity in comparison with Nystatin.
4
a
4b 4c 4d 4e 4f 4g Nystatin
Compound
Zone of inhibition of antifungal activity: (1) Aspergillus
niger and (2) Aspergillus flavus.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
569
ClO
+
EXPERIMENTAL
[M + H] . Found, %: C 57.53; H 2.41. C10
H
5
3
.
Calculated, %: C 57.58; H 2.42.
Melting points were determined in open capillary
tubes. Purity of the compounds was tested by TLC on
silica gel 60 F254 (Merck). Microwave assisted processes
were carried out in a MultiSYNTH series microwave
system (Milestone). IR spectra were recorded in KBr
Synthesis of (E)-3-[3-(2-hydroxyphenyl)-3-oxo-
prop-1-en-1-yl]-4H-chromen-4-ones (3a–3g). a. Con-
ventional heating method. A mixture of a substituted-
2
4
-hydroxy acetophenone 1a–1d (10 mmol) with 4-oxo-
H-chromene-3-carbaldehydes 2a–2d (10 mmol), and
1
on a Perkin-Elmer 1800 spectrophotometer. H NMR
TEA (20 mmol) in ethanol was refluxed for 2.8–3.5 h.
The process was monitored by TLC. Upon completion
of the reaction, the mixture was poured into ice cold
water. The product was extracted with EtOAc and
dried over Na SO . The solvent was evaporated and
spectra were measured on a Varian VNMRS-400
spectrometer using TMS as an internal standard. Mass
spectra were measured on a GCMS-QP 1000 mass
spectrometer.
2
4
Synthesis of 4-oxo-4H-chromene-3-carbaldehydes
2a–2d). The Vilsmeier–Haack adduct was synthesized
the residue was purified by column chromatography to
afford pure (E)-3-[3-(2-hydroxyphenyl)-3-oxoprop-1-
en-1-yl]-4H-chromen-4-ones 3a–3g.
(
from POCl (10 mmol) and N,N-dimethylformamide
3
(
25 mmol) at 0°C. A substituted-2-hydroxy aceto-
b. Microwave irradiation method. A mixture of sub-
stituted-2-hydroxy acetophenones 1a–1d (10 mmol)
with 4-oxo-4H-chromene-3-carbaldehydes 2a–2d
phenone 1a–1d, (1.0 mmol) was added to the
Vilsmeier–Haack adduct and the mixture was stirred at
room temperature for 16–18 h. Progress of the reaction
was monitored by TLC. Upon completion of the
process, the reaction mixture was poured into ice cold
water and the white product was filtered off and dried.
The products 2a–2d were purified by recrystallization
from petroleum ether : ethyl acetate mixture.
(
10 mmol), and TEA (20 mmol) in ethanol was sub-
jected to microwave irradiation at 160 W for 4–5 min
with intervals every 30 s. The process was monitored
by TLC. Upon completion of the reaction the mixture
was poured into ice cold water. The product was
extracted with EtOAc and dried over Na SO . The
2
4
4
-Oxo-4H-chromene-3-carbaldehyde (2a). Yield
solvent was evaporated and the residue was purified by
column chromatography to afford pure (E)-3-[3-(2-
hydroxyphenyl)-3-oxoprop-1-en-1-yl]-4H-chromen-4-
ones 3a–3g.
–1
8
5%, mp 148–150°C. IR spectrum, ν, cm : 1694 (C=O).
H NMR spectrum, δ, ppm: 7.49–7.55 m (2H), 7.74–
.78 m (1H), 8.30 d.d (1H, J = 8.0 Hz, 1.2 Hz), 8.55 s
1H), 10.36 s (1H); M 174 [M + H] . Found, %: C
1
7
(
6
+
3
-[(E)-3-(2-Hydroxyphenyl)-3-oxoprop-1-enyl]-
8.91; H 3.52. C H O . Calculated, %: C 68.97; H 3.47.
–1
10
6
3
4
H-chromen-4-one (3a). IR spectrum, ν, cm : 1637.
1
6
-Methyl-4-oxo-4H-chromene-3-carbaldehyde
H NMR spectrum, δ, ppm: 7.05–7.01 m (2H), 7.60–
7.55 m (2H), 7.76–7.68 m (2H), 7.89–7.85 m (1H),
7.97 d (1H, J = 6.8 Hz), 8.19–8.16 m (1H), 8.53 d (1H,
J = 15.6 Hz), 9.07 s (1H), 12.27 s (1H). M 293 [M +
–1
(
1
7
2b). Yield 85%, mp 153–155°C. IR spectrum, ν, cm :
695 (C=O). H NMR spectrum, δ, ppm: 2.45 s (3H),
.43 d (1H, J = 9.0 Hz), 7.56–7.58 m (1H), 8.10 s
1H), 8.52 s (1H), 10.38 s (1H). M 188.9 [M + H] .
1
+
+
(
H] . Found, %: C 73.92; H 4.10. C H O . Calculated,
1
8
12
4
Found, %: C 70.25; H 4.32. C H O . Calculated, %: C
%: C 73.97; H 4.14.
1
1
8
3
7
0.21; H 4.29.
-Bromo-4-oxo-4H-chromene-3-carbaldehyde
3
-[(E)-3-(2-Hydroxy-5-methylphenyl)-3-oxoprop-
–1
6
1-enyl]-4H-chromen-4-one (3b). IR spectrum, ν, cm :
1640. H NMR spectrum, δ, ppm: 2.33 s (3H), 6.92 d
(1H, J = 8.8 Hz ), 7.39 d (1H, J = 8.4 Hz ), 7.58–7.60 t
(1H, J = 7.6 Hz), 7.68–7.76 m (3H), 7.86–7.90 m (1H),
8.18 d (1H, J = 7.6 Hz), 8.51 d (1H, J = 15.2 Hz), 9.08
–
1
1
(
2c). Yield 81%, mp 182–184°C. IR spectrum, ν, cm :
1
1
691 (C=O). H NMR spectrum, δ, ppm: 7.44 d (1H,
J = 8.8 Hz), 7.84 d.d (1H, J = 1.2 Hz, 8.8 Hz), 8.42 s
+
(
1H), 8.54 s (1H), 10.36 s (1H). M 253 [M + H] .
+
Found, %: C 47.40; H 2.02. C H BrO . Calculated, %:
s (1H), 12.13 s (1H). M 307 [M + H] . Found, %: C
1
0
5
3
C 47.46; H 1.99.
74.52; H 4.65. C19H O . Calculated, %: C 74.50; H 4.61.
14 4
6
-Chloro-4-oxo-4H-chromene-3-carbaldehyde
3-[(E)-3-(2-Hydroxy-5-methylphenyl)-3-oxoprop-
1-enyl]-6-methyl-4H-chromen-4-one (3c). IR spectrum,
ν, cm : 1641. H NMR spectrum, δ, ppm: 2.38 s (3H),
2.45 s (3H), 6.92 d (1H, J = 8.1 Hz), 7.31 d.d (1H, J =
2.1 Hz , 8.4 Hz), 7.42 d (1H, J = 8.4 Hz ), 7.51–7.56 m
–
1
(
1
2d). Yield 80%, mp172-174°C. IR spectrum, ν, cm :
1
–1
1
694 (C=O). H NMR spectrum, δ, ppm: 7.51 d (1H,
J = 8.8 Hz), 7.70 d.d (1H, J = 2.4 Hz, 8.8 Hz), 8.26 d
1H, J = 2.4 Hz), 8.54 s (1H), 10.37 s (1H). M 209
(
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018

5
70
PERVARAM et al.
(
2H), 7.81 s (1H), 8.10 s (1H), 8.21 s (1H), 8.79–8.84
acidified by 2 M hydrochloric acid solution. The
precipitated product was filtered off, washed with ice
cold water, dried, and crystallized from EtOH to gave
3-{(Z)-[3-oxobenzofuran-2(3H)-ylidene]methyl}-4H-
chromen-4-ones 4a–4g.
+
d (1H, J = 15.3 Hz), 12.72 s (1H). M 321 [M + H] .
Found, %: C 75.02; H 5.00. C H O . Calculated, %:
2
0
16
4
C 74.99; H 5.03.
-[(E)-3-(5-Bromo-2-hydroxyphenyl)-3-oxoprop-
1
1
8
3
–1
-enyl]-4H-chromen-4-one (3d). IR spectrum, ν, cm :
637. H NMR spectrum, δ, ppm: 6.99 d (1H, J =
Method 2. Using CuBr in DMSO. CuBr (2 mmol)
2
2
1
and (E)-3-[3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl]-
4H-chromen-4-ones 3a–3g (1 mmol) were added to
DMSO (10 mL). The reaction mixture was heated at
90°C for 2 h. Upon completion of the process (TLC),
the reaction mixture was cooled down to room
temperature and then poured into ice cold water and
stirred for 10–15 min. The precipitated material was
filtered off, washed with ice cold water, dried, and
crystallized from EtOH gave 3-{(Z)-[3-oxobenzofuran-
.4 Hz ), 7.57–7.59 m (1H), 7.64–7.67 m (2H), 7.75 d
1H, J = 8.0 Hz), 7.85–7.87 m (1H), 7.96 s (1H), 8.17
(
d (1H, J = 8.0 Hz), 8.38 d (1H, J = 15.6 Hz), 9.08 s
–
(1H), 11.86 s (1H). M 369 [M – H] . Found, %: C 58.29;
H 3.03. C H BrO . Calculated, %: C 58.24; H 2.99.
18
11
4
6
-Bromo-3-[(E)-3-(5-bromo-2-hydroxyphenyl)-3-
oxoprop-1-enyl]-4H-chromen-4-one (3e). IR spec-
trum, ν, cm : 1642. H NMR spectrum, δ, ppm: 7.54
d.d (1H, J = 2.8 Hz , 9.2 Hz), 7.60 d (1H, J = 15.2 Hz),
–
1
1
2(3H)-ylidene]methyl}-4H-chromen-4-ones 4a–4g.
7
(
.60 d (1H, J = 8.8 Hz), 7.82–7.78 m (2H), 7.80 d.d
1H, J = 2.4 Hz, 8.6 Hz), 8.04 d (1H, J = 2.4 Hz), 8.35
d (1H, J = 15.2 Hz), 9.09 s (1H), 11.75 s (1H). M 449
3-{(Z)-[3-Oxobenzofuran-2(3H)-ylidene]methyl}-
4H-chromen-4-one (4a). IR spectrum, ν, cm : 1702.
H NMR spectrum, δ, ppm: 7.27 s (1H), 7.31 d (1H,
–
1
1
+
[
M + H] . Found, %: C 48.05; H 2.28. C H BrO .
J = 8.4 Hz), 7.37 s (1H), 7.44–7.53 m (2H), 7.65–7.74
m (2H), 7.82 d (1H, J = 7.2 Hz), 8.31 d (1H, J =
1
8
10
4
Calculated, %: C 48.03; H 2.24.
1
3
8
.0 Hz), 9.08 s (1H). C NMR spectrum, δ , ppm:
C
3
-[(E)-3-(5-Chloro-2-hydroxyphenyl)-3-oxoprop-
–
1
102.2, 112.7, 118.1, 118.2, 121.7, 123.6, 123.8, 124.8,
1
1
8
7
-enyl]-4H-chromen-4-one (3f). IR spectrum, ν, cm :
639. H NMR spectrum, δ, ppm: 7.05 d (1H, J =
1
125.8, 126.5, 134.1, 136.9, 147.2, 155.9, 158.8, 165.5,
+
1
4
75.1, 183.6. M 291 [M + H] . Found, %: C 73.92; H
.8 Hz), 7.59–7.55 m (2H), 7.66 d (1H, J = 15.6 Hz),
.75 d (1H, J = 8.0 Hz), 7.84–7.89 m (2H), 8.17 d.d
.10. C H O . Calculated, %: C 73.97; H 4.14.
1
8
10
4
(
9
1H, J = 1.2 Hz, 7.6 Hz), 8.39 d (1H, J = 15.6 Hz),
.08 s (1H), 11.85 s (1H). M 325 [M – H] . Found, %:
3-{(Z)-[5-Methyl-3-oxobenzofuran-2(3H)-ylidene]-
–
–1
methyl}-4H-chromen-4-one (4b). IR spectrum, ν, cm :
1
C 66.11; H 3.45. C H ClO . Calculated, %: C 66.17;
1704. H NMR spectrum, δ, ppm: 2.38 s (3H), 6.99 s
18
11
4
H 3.39.
-Chloro-3-[(E)-3-(5-chloro-2-hydroxyphenyl)-3-
oxoprop-1-enyl]-4H-chromen-4-one (3g). IR spec-
trum, ν, cm : 1652. H NMR spectrum, δ, ppm:, 7.04
d (1H, J = 8.8 Hz) 7.56 d.d (1H, J = 2.4 Hz, 8.8 Hz),
(1H), 7.46 (1H, d, J = 8.4 Hz), 7.55–7.66 m (3H), 7.75
d (1H, J = 8.4 Hz), 7.89 t (1H, J = 7.6 Hz), 8.16 d (1H,
6
13
J = 8.0 Hz), 9.23 s (1H). C NMR spectrum, δ , ppm:
C
–
1
1
21.0, 102.0, 112.7, 118.1, 118.2, 120.1, 123.8, 124.6,
1
1
7
3
25.3, 125.8, 126.5, 134.1, 147.2, 149.2, 155.9, 158.7,
65.9, 175.2, 183.3. M 305 [M + H] . Found, %: C
+
7
.63 d (1H, J = 15.6 Hz ), 7.81–7.84 m (2H), 7.91 d.d
1H, J = 2.4 Hz , 8.8 Hz), 8.09 d (1H, J = 2.4 Hz), 8.37
d (1H, J = 15.6 Hz), 9.10 s (1H), 11.78 s (1H). M 359
4.94; H 3.99. C H O . Calculated, %: C 74.99; H
1
9
12
4
(
.97.
6-Methyl-3-{(Z)-[5-methyl-3-oxobenzofuran-2(3H)-
ylidene]methyl}-4H-chromen-4-one (4c). IR spec-
–
[
M – H] . Found, %: C 59.88; H 2.83. C H Cl O .
18 10 2 3
Calculated, %: C 59.86; H 2.79.
–1
1
trum, ν, cm : 1707. H NMR spectrum, δ, ppm: 2.38 s
Synthesis of 3-{(Z)-[3-oxobenzofuran-2(3H)-yl-
idene]methyl}-4H-chromen-4-ones (4a–4g). Method
(
7
3H), 2.45 s (3H), 7.00 s (1H), 7.45 d (1H, J = 8.4 Hz),
.57–7.71 m (4H), 7.95 s (1H), 9.21 s (1H). C NMR
1
3
1
. Using Hg(OAc) in pyridine. Mercury (II) acetate
2
spectrum, δ , ppm: 20.7, 20.9, 102.1, 112.3, 117.9,
C
(
1 mmol) was dissolved in pyridine (10 mL) upon
1
1
18.0, 122.8, 125.1, 125.8, 126.8, 131.4, 135.3, 137.1,
cooling and to this solution a (E)-3-[3-(2-hyd-
roxyphenyl)-3-oxoprop-1-en-1-yl]-4H-chromen-4-ones
37.9, 147.4, 148.7, 153.2, 158.7, 164.0, 176.6, 182.8.
+
M 319 [M + H] . Found, %: C 75.44; H 4.44.
3
a–3g (1 mmol) was added. The mixture was refluxed
C H O . Calculated, %: C 75.46; H 4.43.
2
0
14
4
for 5 h. Upon completion of the process (TLC), the
reaction mixture was cooled down to room tem-
perature and then poured into ice cold water and
3-{(Z)-[5-Bromo-3-oxobenzofuran-2(3H)-ylidene]-
–
1
methyl}-4H-chromen-4-one (4d). IR spectrum, ν, cm :
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018

SYNTHESIS AND ANTIMICROBIAL ACTIVITY
571
1
1
7
8
9
1
1
707. H NMR spectrum, δ, ppm: 7.05 s (1H), 7.56–
activity was tested according to the “well plate or disc
diffusion method” [15, 16]. The minimum inhibitory
concentration was determined using the tube dilution
techniques [15, 16]. Various concentrations of each
compound were prepared using single dilution method.
The least concentration of each compound that did not
permit any visible growth or turbidity of the inoculated
test organisms in broth culture was taken as the
minimum inhibitory concentration in each case.
.60 m (2H), 7.76 d (1H, J = 8.4 Hz), 7.90 t (1H, J =
.0 Hz), 7.98–8.00 m (2H), 8.17 d (1H, J = 8.0 Hz),
.28 s (1H). C NMR spectrum, δ , ppm: 103.2, 113.9,
18.1, 124.3, 125.6, 126.9, 128.9, 135.0, 136.1, 147.7,
55.6, 158.7, 165.1, 174.9, 182.5. M 369 [M + H] .
13
C
+
Found, %: C 59.61; H 2.93. C H BrO . Calculated, %:
1
8
9
4
C 59.55; H 2.89.
-Bromo-3-{(Z)-[5-bromo-3-oxobenzofuran-2(3H)-
ylidene]methyl}-4H-chromen-4-one (4e). IR spec-
trum, ν, cm : 1709. H NMR spectrum, δ, ppm: 7.14 s
1H), 7.72–7.78 m (3H), 7.87 d (1H, J = 2.4 Hz), 8.03
d.d (1H, J = 2.8 Hz , 9.2 Hz), 8.18 d (1H, J = 2.4 Hz),
.25 s (1H). C NMR spectrum, δ , ppm: 101.9, 112.3,
19.0, 120.4, 121.0, 121.9, 123.5, 123.6, 124.8, 125.7,
31.0, 134.2, 136.4, 147.3, 155.9, 156.8, 164.5, 174.6,
6
Antifungal activity. Antifungal activity was studied
by the well plate or disc diffusion method [17, 18]. The
MIC was determined by the broth micro dilution method
using 96-well micro-plates [17, 18]. Each sample
(1.0 mg) was dissolved in DMSO (1 mL) to obtain
1000 μg/mL stock solution. Nystatin was used as a
positive control. Plates were incubated at 37°C for 24 h.
–
1
1
(
13
9
1
1
1
C
+
83.2. M 447 [M + H] . Found, %: C 48.28; H 1.83.
C H BrO . Calculated, %: C 48.25; H 1.80.
CONCLUSIONS
1
8
8
4
3
-{(Z)-[5-Chloro-3-oxobenzofuran-2(3H)-ylidene]-
A series of aurones have been synthesized and
tested for their antibacterial and antifungal activities.
–1
methyl}-4H-chromen-4-one (4f). IR spectrum, ν, cm :
1
1
7
8
9
1
1
704. H NMR spectrum, δ, ppm: 7.06 s (1H), 7.60–
.62 m (2H), 7.74 d (1H, J = 8.0 Hz), 7.92 t (1H, J =
.2 Hz), 7.98–8.10 m (2H), 8.16 d (1H, J = 7.8 Hz),
.26 s (1H). C NMR spectrum, δ , ppm: 103.5, 114.1,
18.3, 124.5, 125.9, 126.6, 129.6, 134.3, 136.7, 147.2,
The aurones were synthesized using Hg(OAc)
2
and
CuBr . The former led to higher yields of the products
2
.
Positions of the substituents and their electronic nature
seem to play an important role in biological activity of
the synthesised compounds. The compounds 4c and 4e
are more potent and the compound 4g is moderately
potent for pathogenic bacteria and fungi compared to
the standard drugs.
13
C
+
55.9, 158.9, 164.2, 175.0, 182.3. M 325 [M + H] .
Found, %: C 66.62; H 2.83. C H ClO . Calculated, %:
1
8
9
4
C 66.58; H 2.79.
-Chloro-3-{(Z)-[5-chloro-3-oxobenzofuran-2(3H)-
ylidene]methyl}-4H-chromen-4-one (4g). IR spectrum,
6
ACKNOWLEDGMENTS
–
1
1
ν, cm : 1710. H NMR spectrum, δ, ppm: 7.01 s (1H),
.62 d (1H, J = 8.8 Hz), 7.84–7.90 m (3H), 7.94 d.d
1H, J = 2.4 Hz , 9.2 Hz), 8.10 d (1H, J = 2.8 Hz), 9.29
s (1H). C NMR spectrum, δ , ppm: 102.8, 112.5,
18.5, 120.3, 120.5, 121.0, 123.6, 123.7, 124.5, 124.6,
25.9, 131.6, 134.5, 136.8, 147.5, 156.2, 157.4, 164.7,
The authors are thankful to the Head, Department
of Chemistry, Jawaharlal Nehru Technological University
and Osmania University, Hyderabad for providing
Laboratory facilities and we also thankful to the Director,
Central Facilities for Research and Development,
Osmania University, and Hyderabad for providing
spectral analysis facilities.
7
(
1
3
C
1
1
1
2
+
74.7, 183.4. M 359 [M + H] . Found, %: C 60.22; H
.31. C H Cl O . Calculated, %: C 60.19; H 2.25.
1
8
8
2
3
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