A facile access to novel heterocyclic analogues of chalcone from newly synthesized ketone containing isoxazole and a benzoxazinone ring

Article abstract of DOI:10.1039/c6ra08710h

A series of novel heterocyclic analogs of chalcone containing isoxazole and a benzoxazinone ring as a prime motif was rationally designed and synthesized. There is nothing in the literature about such α,β-unsaturated ketones. These compounds were synthesi

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ARTICLE
A facile access to novel heterocyclic analogues of chalcone from
newly synthesized ketone containing isoxazole and
benzoxazinone ring
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Nishant Verma*, Sumit Kumar and Naseem Ahmed*
www.rsc.org/
A series of novel heterocyclic analogs of chalcone containing isoxazole and benzoxazinone ring as a prime motif was
rationally designed and synthesized. There is nothing in the literature about such α, β-unsaturated ketones. These
compounds were synthesized by Claisen–Schmidt condensation reaction of its ketone precursor with different aromatic
aldehyde using ethanol as solvent and piperidine as a base. Our procedure offer easy access to isoxazole and
benzoxazinone based chalcone derivatives providing yields in the range of 81 – 93% within 16 min under mild condition.
Out of 21, 11 compounds were screened for their antibacterial activities. Among the screened compounds, compounds
-
1
5
aj, 5ak and 5bj showed excellent antibacterial activities with MIC: 0.34, 0.59 and 0.74 mg.mL respectively as compared
to standard drug.
3
i
3j
human cloned dopamine D4 receptor, antagonist activity and
3
k
1
. Introduction
antinociceptive activity .
The benzoxazinone moiety has been extensively studied due to
prevalence of these moieties in the cores of natural products and
pharmaceuticals. The benzoxazinones produced by a wide range of
plants including commercially important cereal crops such as rye,
Chalcones are important naturally occurring plant constituents and
common structures and precursor in biologically active
heterocycles, in particular, of benzothiazepines, pyrazolines,
pyrimidines, isoxazolines flavonoids and isoflavonoids. These
display a wide range of pharmaceutical, extensive agricultural and
4
maize and wheat . Benzoxazinones are well-known to show a broad
5
a
1
a
1b
range of biological properties including antifeedant ,
synthetic applications such as, anti-inflammatory, antifungal,
5
b
5c
5d
1
c
1d
1e
1f
antimicrobial, antiphlogistic and insecticidal effects . These are
1j known for their unique chemical motif with potential
pharmaceutical activity and have been recognised as “privileged
antibacterial, antiviral, antiprotozoal, anticancerous, anti-
1
g
1h
1i
tubercular, hyperglycemic agents, agrochemicals, scavenging,
1
k
and PET scan imaging probes, . From synthetic prospect, chalcone
derivatives are gaining more importance due to their critical role in
the organic synthesis. Chalcone moiety containing nitrogen
heterocycles have been reported as active compounds against
6
scaffold” in terms of drugs design .
Chalcones on integration with different biologically active
frameworks have always shown comparative more potent activities;
like benzfuran chalcones have exhibited both antioxidant and
antibacterial activity. Benzimidazole-‘‘a heterocyclic scaffold’’ is a
widely used medicinal component due to its broad spectrum of
biological activities. For example, there are some recent reports on
the efficient ultrasound-assisted or solvent-free Claisen–Schmidt
synthesis of heterocycle-chalcone hybrids, such as quinoline
2
a
herpes simplex virus-1(HSV-1) and human immunodeficiency virus
2
b
-1(HIV-1) . These compounds also exhibit antiproliferative activity
2
c
towards leukemia cell lines .
Isoxazole derivatives exhibit a unique and interesting class of five-
membered heterocycle because of their synthetic versatility and
effective biological activities. Heterocyclic compounds with
isoxazole moiety were found to be valuable intermediates for
medicinal drugs. They are related with a broad spectrum of
7
8
chalcones, pyrazole chalcones and quinoline-appended ferrocenyl
9
chalcones . Heterocyclic rings especially the benzoxazinone and
3
a
isoxazole rings, represent an expedient choice for the synthesis of
3f pharmaceutical compounds with different activities and noble
safety profiles. As a consequence, the remarkable bioactivity along
with the unique structural features displayed by these heteroaryl-
based chalcones makes them a particularly attractive target for the
synthetic efforts.
biological and pharmaceutical activities such as anti-inflammatory ,
3
b
3c
3d
3e
anticancer, analgesic, antiviral, antimicrobial, anthelmintic,
3
g
3h
anticonvulsant, antidepressant, potent selective agonists of the
a.
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-
2
47667 Uttarakhand, India.
Fax: +91-1332 285745, E-mail: nishant.sailove@gmail.com, nasemfcy@iitr.ac.in
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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On account of these aspects and in order to expand the structure condensation reaction with the aim of providing a simple method
diversity for current medicinal chemistry needs, we would like to for the synthesis of novel isoxazole and benzoxazinone-based
report here an efficient, and the detailed synthetic approach for the chalcone derivatives.
synthesis of novel isoxazole and benzoxazinone-based chalcone
derivatives, namely 6-bromo-4-(3-(3-(4-substitutedphenyl)acryloyl)-
2
. Results and discussion
4
,5-dihydroisoxazol-5-yl)-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-
one through Claisen–Schmidt condensation reaction of 4-((3-acetyl-
,5-dihydroisoxazol-5-yl)methyl)-6-bromo-4-methyl-1H-
2
.1 Chemistry
4
Chalcones 5aa-ak and 5ba-bj were synthesized via Claisen–Schmidt
condensation reaction with substituted benzaldehyde and 5a or 5b,
benzo[d][1,3]oxazin-2(4H)-one and various aromatic aldehydes with
piperidine as base and ethanol as a solvent for 10-16 min under
microwave irradiation providing 81–93% yield.
0
piperidine in ethanol, at 80 C for 15 min under microwave
irradiation (Scheme 1). After completion of the reaction, the
mixture was filtered to collect the precipitates and purification by
recrystallization affords the pure chalcones 5aa-ak and 5ba-bj in
Many methods have been developed for the synthesis of chalcone
derivatives, to the best of our knowledge, the synthesis of isoxazole
and benzoxazinone-based chalcones under microwave irradiation
has not been reported. To contribute to the development of
environmentally benign organic chemistry, and in the context of our
ongoing work on the ‘green’ synthesis of potential biologically
8
1–93% yield. The compounds 5aa-ak and 5ba-bj were obtained
from corresponding ketones (5a and 5b). The intermediate ketones
were produced in four-step synthesis (Scheme 1).
a
1
0
active heterocycles, we have explored the above Claisen– Schmidt
Scheme 1 Synthesis of Benzoxazinone-isoxazole endowed chalcone
0
Reagents and condition: (a) NBS, acetonitrile, 3h (b) allyl or vinylmagnesium bromide, THF, -78 C, inert, 5h (c) carbonyldiimidazole, THF, 60
0
0
0
C, 12h (d) Ceric ammonium nitrate, acetone, 60 C, overnight (e) ethanol, piperidine, MW 80 C, 10-16 min.
In the first step, the commercially available starting material 2- obtain the final compounds 5aa-ak and 5ba-bj in good to excellent
1
3
aminoacetophenone (1) was transformed into 5-bromo-2- yields (81–93%) . To find optimum protocol for the transformation
aminoacetophenone (2) by using N-bromosucciniimide in various conditions for a prototypical reaction were explored as
0
11
acetonitrile at 0 C in high yields (92%) . Then compound 2 was shown in Table 1.
treated with vinyl or allylmagnesium bromide to furnish Initially, the reaction was carried out in methanol and ethanol in the
0
0
corresponding products 3a or 3b respectively via Grignard reaction presence of NaOH, KOH at 60 C and in t-BuOK at 80 C for 6h (Table
in excellent yield (95%). Next step of the synthesis was the 1, entries 1, 2, 3). The reaction did not proceed, instead some
conversion of compound 3a or 3b to their corresponding products decomposed products were obtained. Then different bases were
4
a or 4b respectively using carbonyldiimidazole in THF in 96% examined and it was observed that pyridine promoted the reaction
1
2
yield . They were then treated with ceric ammonium nitrate and in low yields (45%, Table 1, entry 4). Among the bases screened,
acetone to obtain compounds 5a or 5b which were treated with piperidine was found to be the most effective catalyst. The
0
various substituted aldehydes in ethanol/piperidine at 80 C to
2
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a-e
influence of solvent system was then evaluated. tert-Butanol Table 2. Optimization of reaction temperature and conditions.
furnished the desired product in low yield (55%, Table 1, entry 5).
a
Table 1. Optimization of base and solvent.
0
e
Entry Condition
Temp. ( C)
Time (min)
Yield(%)
d
1
2
3
4
5
6
7
8
9
1
1
grinding
Rt
1h
6h
8h
6h
8h
20
15
15
15
12
10
12
-
b
CH
80
70
90
60
70
80
85
90
80
80
80
85
71
80
b
b
CH
Entry Solvent
Base
Base
Temp.
Time Yield
b
0
CH
equiv.
( C)
(h)
6
(%)
-
b
d
CH
67
1
MeOH
EtOH
NaOH
1
1
1
2
2
1
60
c
MW
69
90
88
84
92
79
2
3
4
5
6
7
8
KOH
60
6
-
c
MW
t-BuOH
EtOH
t-BuOK
Pyridine
Piperidine
Piperidine
80
5
-
c
MW
reflux
reflux
reflux
reflux
reflux
reflux
6
45
55
67
72
85
85
c
MW
t-BuOH
EtOH
7
c
0
1
2
MW
8
c
MW
EtOH
Piperidine 1.5
8
c
d
1
a
MW
73
EtOH
Piperidine
2
6
General condition: 4-(3-acetyl-4,5-dihydroisoxazol-5-yl)-6-bromo-
-methyl-1H-benzo[d][1,3]oxazin-2(4H)-one 5a (1 mmol),
9
a
EtOH
Piperidine
3
8
4
General condition: 4-(3-acetyl-4,5-dihydroisoxazol-5-yl)-6-bromo-
b
c
benzaldehyde a (1 mmol); Conventional heating; Anton Paar
4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-one 5a (1 mmol), 4-fluro
d
Monowave 300 reactor; Reaction carried out in neat condition;
benzaldehyde a (1 mmol).
e
b
Isolated yield.
Isolated yield.
For comparison, the same reaction was subjected to microwave
irradiation and effect of irradiation time and temperature on the
efficiency and yield were briefly investigated. First, the effect of
irradiation temperature was briefly examined. It was observed that
To our delight, by using ethanol as solvent, moderate yield was
achieved (67%, Table 1, entry 6). Regarding the influence of the
solvent in this reaction, EtOH was achieved as optimal solvent
(Table 1, entry 8). It can be easily rationalized that use of ethanol
0
yield of 5aa at 70 C (69%) was abruptly increased to 90% by
enhances the solubility of reagents and thus increased the product
yield. It is important to note that when the amount of piperidine is
increased from 1 to 1.5 eq., an increase in the yield was observed to
0
increasing the irradiation temperature up to 80 C, but it became
0
lower when the microwave temperature exceeded 80 C (Table 2,
0
entries 6, 7, 8, 9). Thus, 80 C was chosen as the optimum
7
2% (Table 1, entry 7). Further increase in the amount of piperidine
to 2 eq. the desired product 5aa was delivered in 85% yield (Table
, entry 8). However, when 3 eq. of piperidine was taken in the
reaction system, the product yield remained unchanged (85%, Table
, entry 9).
With the optimal reaction condition regarding base and solvent
irradiation temperature for 5aa. Then the effect of microwave
irradiation time was studied, and 12 min was found to be the
optimized reaction time for the formation of 5aa. So, we led to
1
0
conclude that microwave irradiation at 80 C for 12 minutes was the
1
optimal condition for the reaction to get best yield of the product.
Using microwave irradiation, an improvement in terms of yields and
reaction time was achieved,
in hands, we thought to explore different reaction conditions and
temperature for the reaction (Table 2). The physical grinding of
substrates with piperidine in a mortar and pestle for 1 h (monitored
by TLC) without any solvent at room temperature did not result in
appreciable yield of the product (Table 2, entry 1). The same
On the basis of these optimized conditions, various
combinations of novel ketone 4a and 4b and substituted
benzaldehydes were employed for the Claisen–Schmidt
condensation reaction, allowing the reaction to be completed
within 16 min in good yields of 81–93% and also high purities (Table
0
reaction took around 6 h under conventional heating (80 C) to
afford 5aa in 85% yield as discussed above (Table 2, entry 2).
3
).
The purified products were characterized by FTIR, H NMR,
NMR, and HRMS. The IR spectra of compounds showed the
However, increase or decrease in temperature of the reaction
1
13
0
C
system to 70 or 90 C, a decrease in the yield was observed (Table
2, entry 3, 4). On the other hand, when the same reaction is done
-1
characteristic band: the ν(C=O) peak observed at 1702 cm shifts to
under solvent free thermal heating condition, the desired product
was furnished in moderate yield (67% Table 2, entry 5).
–1
a lower frequency of 1636–1655 cm in chalcones. This is due to
the conjugation of the π-electrons of the benzene moiety with
those of the ethylene moiety in the enone linkage.
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a,
Table 3. List of the synthesized benzoxazinone-isoxazole endowed chalcone derivatives. *
b
Entry
ketone
aldehyde
product
Time (min)
11
Yield (%)
1
5a
92
89
87
2
3
5a
5a
12
12
4
5
5a
5a
15
15
85
85
6
7
5a
5a
16
10
83
93
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8
9
5a
5a
10
10
88
84
1
1
0
1
5a
5a
14
14
85
87
1
2
5b
11
86
1
3
5b
12
84
1
1
4
5
5b
5b
15
15
86
82
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1
1
6
7
5b
5b
18
18
80
75
1
1
2
2
8
9
0
1
5b
5b
5b
5b
10
10
10
14
87
89
88
86
a
General condition: 4-(3-acetyl-4,5-dihydroisoxazol-5-yl)-6-bromo-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-one 5a (1 mmol),
benzaldehyde (a-k) (1 mmol), piperidine (2 mmol), ethanol; *Anton Paar Monowave 300 reactor. Irradiation Power: 850 W;
0
b
Ramp time: 1 min. 70 °C; holding temp: 80 C; Isolated yield.
2
.2. Biological activity
The newly synthesized compounds were evaluated for their in
vitro antibacterial activity against S. aureus and B. subtilis as
examples of Gram-positive bacteria and E. coli and S. flexneri as
examples of Gram-negative bacteria. Out of these (Table 4) showing
only 11 most potent antibacterial active compound.
6
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2
.2.1. Antibacterial activity. As seen in the Table 4, compound 5aj irradiation as
a
source of energy, in short reaction time,
−1
(MIC: 0.34 mg.ml ) and compounds 5af, 5ag, 5ak, 5bg, 5bj (MIC: contemplating the principles of green chemistry. Compounds 5aj,
−1
1.78, 1.42, 0.59, 1.36, 0.74 mg.ml ) have shown better antibacterial 5ak and 5bj exhibited the highest biological activity toward Gram-
activity than positive controls against S. aureus. In case of B. subtilis, positive S. aureus and Gram-negative E.coli bacteria with MIC: 0.34,
-1
all compounds have shown lower activity than ampicillin. 0.59 and 0.74 mg.mL respectively as compare to standard drug.
Moreover, compounds 5af, 5aj, 5ak, 5bg, 5bj (MIC: 3.10 - 3.12
−1
mg.ml ) were found to be equally potent as cefadroxil against B.
subtilis. Compounds 5af, 5ag, 5aj, 5ak, 5bg, 5bj (MIC: 0.34 – 1.45
4
. Experimental
−1
mg.ml ) have shown better activity than positive controls against E.
All the required chemicals were purchased from Merck and Aldrich
Chemical Company. Pre-coated aluminium sheets (silica gel 60
F254, Merck) were used for thin-layer chromatography (TLC) and
spots were visualized under UV light.IR spectra were recorded with
−1
coli while compounds 5af and 5ag (MIC: 1.45 and 1.53 mg.ml )
have shown approx. equal activity to the reference drugs.
Compounds 5aj and 5bj have shown admirable antibacterial activity
−
1
1
13
(
MIC: 0.95 and 1.55 mg.ml ) against Shigella flexneri compared to
ampicillin and cefadroxil. Thus, the hydroxy group on ring D carrying
KBr on Thermo Nicolet FT-IR spectrophotometer. H NMR and
NMR spectra were recorded respectively on Bruker Spectrospin DPX
00 MHz and Bruker Spectrospin DPX 125 MHz spectrometer using
CDCl as a solvent and trimethylsilane (TMS) as an internal standard.
C
−1
a compounds 5aj and 5bj have shown excellent (MIC: 0.34 mg.ml )
5
−1
to good (MIC: 1.78 mg.ml ) activity against S. aureus. Against B.
subtilis also, the methoxy group carrying compounds 5af and 5bf
3
Splitting patterns are designated as follows; s = singlet, d = doublet,
m = multiplet, br = broad. Chemical shift (δ) values are given in
ppm. High-resolution mass spectra (HRMS) were obtained on a
Brüker micrOTOF™-Q II mass spectrometer (ESIMS).
−1
have shown (MIC: 3.10 - 3.75 mg.ml ) antibacterial activity to the
standard drugs. Against E. coli, compounds 5af, 5ag, 5aj, 5ak, 5bg
and 5bj have shown excellent activity compared to ampicillin and
cefadroxil depending on the methoxy and hydroxyl group. Against
Shigella flexneri, all compounds have shown low activity compared
to the standard drugs without depending on functional groups on
aromatic ring except 5aj and 5bj.
4
.1. Microwave Irradiation Experiment.
All microwave experiments were carried out in a dedicated
Anton Paar Monowave-300 reactor®, operating at a frequency of
2.455 GHz with continuous irradiation power of 0 to 850 W. The
reactions were performed in a G-10 Borosilicate glass vial sealed
with Teflon septum and placed in a microwave cavity. Initially,
microwave of required power was used and temperature was being
ramped from room temperature to a desired temperature. Once
this temperature was attained, the process vial was held at this
temperature for required time. The reactions were continuously
stirred. Temperature was measured by an IR sensor. After the
experiments a cooling jet cooled the reaction vessel to ambient
temperature.
-
1
Table 4. Minimum inhibitory concentration (MIC, mg.mL ) of some
newly synthesized compounds against bacterial strains
Compound
Gram-positive
Gram-negative
E.coli S.flexneri
S.aureus
B.subtilis
3.10
3.42
6.45
7.5
5
af
1.78
1.42
6.2
1.45
1.53
7.8
2.23
2.25
6.5
5ag
ah
5
5
ai
aj
7.1
7.
7.5
5
0.34
0.59
2.12
1.36
6.8
3.12
3.12
3.75
3.12
7.1
0.34
0.59
2.25
1.32
7.2
0.95
1.75
2.15
2.26
7.5
5
ak
bf
5
4
.2. General procedure for synthesis of compounds
.2.1. Preparation of compound 5a and 5b: A mixture of 6-
bromo-4-methyl-4-vinyl-1H-benzo[d][1,3]oxazin-2(4H)-one (4a) or
-allyl-6-bromo-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-one (4b) (5
5
bg
bh
4
5
5
5
bi
bj
7.7
8.2
7.9
8.5
4
0.74
0.78
1.56
3.10
0.39
3.12
0.72
1.56
0.78
1.55
0.78
1.56
mmol) and ammonium cerium(IV) nitrate (2.74 g, 5 mmol) in
acetone (20 ml) was stirred under reflux for 12 h. The reaction
mixture was extracted with EtOAc (50 ml) and washed with aq.
Ampicillin
Cefadroxil
NaHCO
water (2 ×30 ml). The ethereal solution was dried over Na
concentrated in vacuum. The resulting solid was
chromatographed on silica gel. Elution with hexane– EtOAc (8:2)
gave 4-(3-acetyl-4,5-dihydroisoxazol-5-yl)-6-bromo-4-methyl-1H-
benzo[d][1,3]oxazin-2(4H)-one (5a) and 4-((3-acetyl-4,5-
dihydroisoxazol-5-yl)methyl)-6-bromo-4-methyl-1H-
benzo[d][1,3]oxazin-2(4H)-one (5b) as white solid (70%).
3
solution (2 ×30 ml), saturated aq. NaCl (2 ×30 ml), and
3
. Conclusions
2
SO and
4
a
In conclusion, we have developed a convenient and simple method
for the preparation of novel bioactive benzoxazinone-isoxazole-
clubbed chalcone derivatives via the reaction of new ketone
derivatives with substituted aldehydes in the presence of
piperidine. The rapid conversion, excellent yield, and operational
simplicity are great advantages of the proposed method.
Furthermore, the reaction conditions employed include microwave
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4
.2.2. Preparation of Chalcones 5aa-ak and 5ba-bj: Dissolve 1 sterile conditions using bio-safety hood and microtitre plates were
0
mmol of the substituted aldehyde and 1 mmol of the 5a or 5b in 10 incubated at 37 C for 24 h.
mL of ethanol in a G-10 process vial capped with Teflon septum. 2
mmol of piperidine then added to the reaction vial using a
Acknowledgements
micropipette. After a pre-stirring for one minute, the vial was
subjected to microwave irradiation with the initial ramp time of 1
The authors wish to express their gratitude to DST New Delhi
0
minute at 70 °C. The temperature was then raised to 80 C with the
for providing HRMS, NMR facility and CSIR, New Delhi for
awarding SRF to N. V. and S.K.
holding time of 10-16 min. After completion of the reaction, cool
the mixture in an ice-water bath until crystal formation is complete.
Add 10 mL of ice-cold water to the flask and vacuum filter. Wash
the crystals with water followed by ice-cold ethanol. Allow to air- Notes and references
dry. Recrystallize from 95% ethanol if necessary to afford the pure
1
(a) C. Q. Meng, L. Ni, K. J. Worsencroft, Z. Ye, M. D.
chalcones 5aa-ak and 5ba-bj in 81–93% yield.
Weingarten, J. E. Simpson, J. W. Skudlarek, E. M.
Marino, K.-L. Suen, C. Kunsch, A. Souder, R. B. Howard,
C. L. Sundell, M. A. Wasserman, J. A. Sikorski, J. Med.
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4
.3. Characterization data
.3.1. (E)-6-bromo-4-(3-(3-(4-fluorophenyl)acryloyl)-4,5-
dihydroisoxazol-5-yl)-4-methyl-1H-benzo[d][1,3]oxazin-2(4H)-one
5aa)
4
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(
1
Yield: 0.42g (92%) as yellow solid; MP 212-214 °C; H NMR (500
3
MHz, CDCl3, ppm): δ 1.78 (s, 3H), 2.87 – 2.94 (m, 1H), 3.0 – 3.06 (m,
1
H), 3.89 – 3.97 (m, 1H), 6.78 (d, J = 14.0 Hz, 1H), 7.24 (s, 1H), 7.34
d, J = 9.5 Hz, 1H), 7.40 (d, J = 9.5 Hz, 2H), 7.48 (d, J = 6.5 Hz, 2H),
.56 (d, J = 8.5 Hz, 1H), 7.94 (d, J = 14.0 Hz, 1H), 9.67 (s, br, D
(
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2
O
1
3
exchangeable, 1H); C NMR (125 MHz, CDCl
3
, ppm): δ 22.1, 26.7,
8
1
1
4.9, 86.1, 117.0, 120.9, 126.9, 127.5, 129.1, 130.3, 130.9, 131.5,
-1
32.4, 134.0, 138.0, 138.3, 138.8, 153.3, 189.3; FTIR (KBr, v = cm ):
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H
2
4
+
[M+Na] : 481.0175 found : 481.0171.
4
.4. Biological activity
.4.1. Antibacterial assay. Minimum inhibitory concentration
MIC) is the lowest concentration of an antimicrobial compound
2
3
4
(
that inhibits the visible growth of a microorganism. MIC values of
the compounds against bacterial isolates were determined on the
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1
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committee
for
clinical
laboratory
standards
(NCCLS)
1
4
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-1
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0
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-1
each well received 107 cfu.ml of bacterial culture. Appropriate
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DOI: 10.1039/C6RA08710H
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Journal Name
ARTICLE
A facile access to novel heterocyclic analogues of chalcone from
newly synthesized ketone containing isoxazole and
benzoxazinone ring
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Nishant Verma*, Sumit Kumar and Naseem Ahmed*
www.rsc.org/
A series of novel heterocyclic analogs of chalcone containing isoxazole and benzoxazinone ring as a prime
motif was rationally designed and synthesized. There is nothing in the literature about such α, β-unsaturated
ketones. These compounds were synthesized by Claisen–Schmidt condensation reaction of its ketone
precursor with different aromatic aldehyde using ethanol as solvent and piperidine as a base. Our procedure
offer easy access to isoxazole and benzoxazinone based chalcone derivatives providing yields in the range of
8
1 – 93% within 16 min under mild condition. Out of 21, 11 compounds were screened for their antibacterial
activities. Among the screened compounds, compounds 5aj, 5ak and 5bj showed excellent antibacterial
-
1
activities with MIC: 0.34, 0.59 and 0.74 mg.mL respectively as compared to standard drug.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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