Microwave-assisted synthesis of (E)-7-[(1-benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-(3-arylacryloyl)-4-methyl-2H-chromen-2-ones and their antimicrobial activity

Article abstract of DOI:10.1515/hc-2014-0102

Hybrid compounds are relevant products in the structure-activity relationships analysis. A new series of hybrid compounds containing coumarin, 1,2,3-triazole, and chalcone substructures were synthesized and screened for their antimicrobial activity. The s

Full text of DOI:10.1515/hc-2014-0102

Heterocycl. Commun. 2014; 20(5): 293–298
Ashok Dongamanti*, Vijaya Lakshmi Bommidi, Ganesh Arram and Ravi Sidda
Microwave-assisted synthesis of (E)-7-[(1-benzyl-
H-1,2,3-triazol-4-yl)methoxy]-8-(3-arylacryloyl)-
1
4
-methyl-2H-chromen-2-ones and their
antimicrobial activity
Abstract: Hybrid compounds are relevant products in the dyes, anti corrosive agents, photo stabilizers, photo-
structure-activity relationships analysis. A new series graphic materials, and agrochemicals [5].
of hybrid compounds containing coumarin, 1,2,3-tria-
Coumarins are important oxygen-containing fused
zole, and chalcone substructures were synthesized and heterocycles used in drugs and dyes [6, 7]. The inter-
screened for their antimicrobial activity. The structures of esting biological activities of coumarins make them
the synthesized compounds have been established on the attractive targets in organic synthesis. Natural cou-
basis of analytical and spectral data.
marins are known to have antidiabetic activity [8] and
are antioxidant, hepato-protective, antimicrobial, anti-
Keywords: alkyne; azide; chalcone; click chemistry; 1,3- oxidant, anticancer [9], and antiviral agents. Synthetic
dipolar cycloaddition; triazole.
coumarins are of pharmaceutical importance. The
potent antibiotic novobiocin, shown in Figure 1, is a
coumarin derivative [10]. These pharmacological prop-
erties of coumarin aroused our interest in synthesiz-
ing some coumarin derivatives with the aim of testing
their microbiological activity. The compounds with the
backbone of chalcones have been reported to possess
various biological activities such as antimicrobial, anti-
inflammatory, analgesic, antiplatelet, antiulcerative,
antimalarial, anticancer [11], antiviral, antileishmanial,
antioxidant [12], antitubercular [13], antihyperglycemic,
and immunomodulatory properties. They show inhibi-
tion of chemical mediators release [14], inhibition of
leukotriene B4 [15], inhibition of tyrosinase [16], and
inhibition of aldose reductase [17]. Other derivatives
show estrogenic activities [18]. Licochalcone (Figure 1)
exhibits antimalarial activity [19]. Chalcones have also
been used as starting materials for the synthesis of
various chemicals, including plastics, resins, pesticides,
dyes, and pharmaceuticals [20].
DOI 10.1515/hc-2014-0102
Received June 26, 2014; accepted August 14, 2014
Introduction
Heterocyclic compounds containing nitrogen and oxygen
atoms play an important role in agrochemical and phar-
maceutical sciences. A large volume of research has been
carried out on triazoles and their derivatives, which has
proven the pharmacological importance of this heterocy-
clic system. 1,2,3-Triazole and its derivatives have received
considerable attention in the past few decades due to their
chemotherapeuticalvalue.Forexample,(1-benzyl-1H-1,2,3-
triazol-4-yl)methanol and 2-(1-(2-methylbutyl)-1H-1,2,3-
triazol-4-yl)propan-2-ol, shown in Figure 1, are potent
antimicrobial agents [1]. Other 1,2,3 triazole derivatives
exhibit anti-inflammatory, analgesic, local anesthetic,
antiallergic, antineoplastic, antimalarial [2], anti-HIV [3],
and anticancer activities [4]. 1,2,3-Triazole compounds
have also been widely used as synthetic intermediates,
Microwave irradiation (MWI) is used for a variety
of organic syntheses due to short reaction time, easy
workup, and good yields. The microwave oven procedure
is now well established in MORE chemistry [21].
Encouraged by the biological importance of cou-
marins, triazoles, and chalcones, in this report, we
describe the synthesis of (E)-7-[(1-benzyl-1H-1,2,3-
triazol-4-yl)methoxy]-8-[3-arylacryloyl]-4-methyl-2H-
chromen-2-ones 6 by conventional and MWI methods
*
Corresponding author: Ashok Dongamanti, Department of
Chemistry, Osmania University, Hyderabad 500 007, India,
e-mail: ashokdou@gmail.com
Vijaya Lakshmi Bommidi, Ganesh Arram and Ravi Sidda:
Department of Chemistry, Osmania University, Hyderabad 500 007,
India
(
Scheme 1). The products were evaluated for antimicro-
bial activity.
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94ꢀꢀꢀꢀꢁꢀA. Dongamanti et al.: Triazole-coumarin hybrids
N
HO
N
HO
N
N
N
N
(1-benzyl-1H-1,2,3-triazol-4-yl)methanol
2-(1-(2-methylbutyl)-1H-1,2,3-triazol-4-yl)propan-2-ol
HO
MeO
OH
O
O
O
O
O
O
O
OH
O
N
H
O
OH
OH
NH2
Novobiocin
licochalcone
Chalcone moiety
1
,2,3-triazole moiety
O
N
our prototype with coumarin,
chalcone and 1,2,3-triazole
N
O
O
O
N
Coumarin moiety
Figure 1ꢂRepresentative examples of biologically active triazoles, chalcones, and coumarins and a general structure of synthesized
coumarin-chalcone-triazole hybrids.
Route1
O
Me
O
Me
O
Me
N
Br
N
HO
O
O
O
O
O
O
O
O
N3
N
K CO , acetone
CuSO4
2
3
MWI
sodium ascorbate
1
Me
2
Me
3
Me
t
H O, BuOH
2
rt or MWI
Ar-CHO, piperidine
MWI
Ar-CHO, piperidine
MWI
Route 2
Ar
Ar
O
b
Ar
O
O
O
N
a
1
Br
N
HO
O
O
O
O
O
7
O
2
O
N3
N
K CO , acetone
2
3
CuSO4
3
6
4
Me
MWI
5
Me
Me
sodium ascorbate
4a-i
5a-i
6a-i
t
H O, BuOH
2
rt or MWI
a: Ar = Ph
d: Ar = 3,4,5-trimethoxyphenyl
e: Ar = 4-fluorophenyl
f: Ar = 4-(dimethylamino)phenyl
g: Ar = 4-isopropylphenyl
h: Ar = 4-chlorophenyl
i: Ar = 4-methylphenyl
b: Ar = 4-methoxyphenyl
c: Ar = 3,4-dimethoxyphenyl
Scheme 1ꢂ
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A. Dongamanti et al.: Triazole-coumarin hybridsꢂꢁꢀꢀꢀꢂ295
piperidine under MWI conditions gave compounds 6a–i
Results and discussion
in excellent yields. In the second route, the chalcones
4
a–i were synthesized first by the reactions of com-
Chemistry
pound 1 with aryl aldehydes in the presence of piperi-
dine under MWI conditions. Propargylation of chalcones
Herein, we wish to report an efficient, practical, and
high-yielding method for the synthesis of compounds
4
a–i followed by the click reactions of the resultant
intermediate products 5a–i [23] gave the desired prod-
ucts 6a–i. The optimized click reactions were conducted
6
a–i. The starting material 8-acetyl-7-hydroxy-4-methyl-
coumarin (1) was prepared by acetylation of 7-hydroxy-
-methylcoumarin followed by rearrangement of the
in t-BuOH/water (1:1) in the presence of CuSO4·5H O
2
4
and sodium ascorbate under MWI conditions. In both
routes, the use of MWI conditions in each particular step
proved to be superior in terms of shorter reaction times
and yields of products in comparison to the use of con-
ventional conditions. The final steps of the synthesis of
products 6a–i under the two conditions are summarized
in Table 1. Structures of all compounds 6a–i were rig-
resultant 7-acetoxy derivative. The synthesis of the
desired products 6a–i was accomplished by two syn-
thetic strategies shown in Scheme 1. In the first route,
compound 2, prepared by propargylation of 1, was
subjected to the click reaction with benzyl azide using
MWI to give compound 3 [22]. Subsequent condensa-
tion reactions of 3 with aryl aldehydes in the presence of
1
13
orously characterized by IR, H NMR, C NMR, and MS
Scheme 1).
(
Table 1ꢂComparison of yields of compounds 6a–i synthesized
under conventional and MWI conditions.
Antimicrobial activity
Compoundꢁ\
Yield (%)
Route ꢃ
MWI
All compounds 6a–i show antimicrobial activity (Table 2
and Figure 2). Importantly, derivatives 6c and 6d exhibit
excellent activities against the selected bacterial strains
that are superior to the activities of the reference anti-
biotic amoxicillin. Compounds 6b, 6e, and 6h display
good antibacterial activity, and compounds 6f and 6g
are moderately active. The coumarin containing triazole
Route ꢂꢁ
ꢁ
Conventionalꢁ
MWI
Conventionalꢁ
ꢄa
ꢄb
ꢄc
ꢄd
ꢄe
ꢄf
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢄꢅꢃ
ꢊꢈꢃ
ꢊꢋꢃ
ꢄꢆꢃ
ꢄꢅꢃ
ꢄꢈꢃ
ꢄꢅꢃ
ꢄꢇꢃ
ꢄꢋꢃ
ꢆꢇꢃ
ꢆꢅꢃ
ꢆꢉꢃ
ꢆꢉꢃ
ꢊꢊꢃ
ꢆꢈꢃ
ꢊꢅꢃ
ꢊꢅꢃ
ꢊꢅꢃ
ꢅꢈꢃ
ꢇꢈꢃ
ꢇꢈꢃ
ꢇꢅꢃ
ꢅꢈꢃ
ꢇꢈꢃ
ꢌꢈꢃ
ꢇꢈꢃ
ꢅꢈꢃ
ꢉꢅ
ꢅꢊ
ꢉꢈ
ꢅꢅ
ꢉꢈ
ꢅꢅ derivatives 6a and 6i are weakly active in the antibacte-
ꢄg
ꢄh
ꢄi
ꢇꢈ
rial assay. Compounds 6c,d are also more active against
ꢅꢅ
selected fungi that the reference drug mycostatin (Table 2
ꢉꢅ
and Figure 3).
Table 2ꢂAntimicrobial activity of compounds 6a–i.
Compound ꢁ
Zone of inhibition (mm)
Gram-positive bacteria
Gram-negative bacteria
Fungiꢁ
F. oxysporum
S. aureusꢁ
B. subtilis
E. coliꢁ
P. aeruginosa
A. nigerꢁ
P. italicum
ꢄa
ꢄb
ꢄc
ꢄd
ꢄe
ꢄf
ꢄg
ꢄh
ꢄi
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢃ
ꢍꢍꢃ
ꢋꢊꢃ
ꢌꢋꢃ
ꢌꢅꢃ
ꢋꢄꢃ
ꢋꢋꢃ
ꢋꢈꢃ
ꢋꢅꢃ
ꢍꢄꢃ
ꢌꢈꢃ
–ꢃ
ꢈꢊꢃ
ꢍꢍꢃ
ꢍꢌꢃ
ꢍꢅꢃ
ꢍꢍꢃ
ꢈꢆꢃ
ꢈꢊꢃ
ꢍꢈꢃ
ꢈꢉꢃ
ꢍꢋꢃ
–ꢃ
ꢍꢈꢃ
ꢋꢊꢃ
ꢌꢍꢃ
ꢌꢌꢃ
ꢋꢄꢃ
ꢋꢌꢃ
ꢋꢋꢃ
ꢋꢌꢃ
ꢍꢇꢃ
ꢌꢈꢃ
–ꢃ
ꢈꢇꢃ
ꢈꢆꢃ
ꢍꢍꢃ
ꢍꢇꢃ
ꢍꢈꢃ
ꢈꢆꢃ
ꢈꢄꢃ
ꢈꢊꢃ
ꢈꢄꢃ
ꢍꢈꢃ
–ꢃ
ꢈꢊꢃ
ꢍꢍꢃ
ꢍꢌꢃ
ꢍꢉꢃ
ꢍꢈꢃ
ꢈꢆꢃ
ꢈꢊꢃ
ꢍꢈꢃ
ꢈꢆꢃ
–ꢃ
ꢍꢇꢃ
ꢍꢊꢃ
ꢋꢍꢃ
ꢋꢇꢃ
ꢍꢆꢃ
ꢍꢄꢃ
ꢍꢉꢃ
ꢍꢉꢃ
ꢍꢄꢃ
–ꢃ
ꢍꢄ
ꢋꢌ
ꢋꢄ
ꢌꢈ
ꢋꢇ
ꢍꢊ
ꢍꢆ
ꢋꢈ
ꢍꢊ
–
Amoxicillin ꢃ
Mycostatin ꢃ
ꢍꢋꢃ
ꢋꢈꢃ
ꢋꢅ
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96ꢀꢀꢀꢀꢁꢀA. Dongamanti et al.: Triazole-coumarin hybrids
Antibacterial activity
Antibacterial activity
4
3
3
2
2
1
1
0
5
0
5
0
5
0
5
0
35
Aspergillus
niger
Staphylococcus
aureus
3
2
0
5
Bacillus subtilis
Penicillium
italicum
20
15
Echerichia coli
1
0
5
0
Fusarium
oxysporum
Pseudomonas
aeruginosa
Compound
Compound
Figure 2ꢂAntibacterial activity of compounds 6a–i.
Figure 3ꢂAntifungal activity of compounds 6a–i.
Synthesis of compounds 6a–i from the substrate 3
Conclusions
Conventional methodꢀA mixture of 8-acetyl-7-[(1-benzyl-1H-1,2,3-tri-
azol-4-yl)methoxy]-4-methyl-2H-chromen-2-one (3, 1 mmol), an aro-
An efficient microwave synthesis of 1,2,3-triazole deriva-
tives was carried out successfully under mild reaction con- matic aldehyde (1 mmol), and few drops of piperidine in ethanol (20
ditions. All final compounds were investigated for their mL) was stirred at room temperature for 24 h. Progress of the reaction
was monitored by TLC. Af er completion of the reaction, the mixture
in vitro antimicrobial activity. Compounds 6b, 6c, 6d,
was diluted with cold water and acidified with diluted hydrochloric
6
e, and 6h show antimicrobial activity against selected
acid. The resulting precipitate was filtered, dried, and crystallized
microorganisms compared with the reference drugs.
from ethanol to afford pure chalcone 6a–i.
Microwave irradiationꢀThe mixture described above was placed in
a Teflon vial with a screw cap and subjected to MWI at 100 W for
Experimental
5
–6 min. Progress of the reaction was monitored by TLC. Workup and
purification of the product 6a–i were conducted as described above.
Melting points were determined in open capillaries using an electrical
melting point apparatus and are uncorrected. Microwave reactions
were carried out in a multi-SYNTH series microwave system (Mile-
stone). The IR spectra were recorded in KBr pellets on a Shimadzu
(
E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-cinnamoyl-4-
methyl-2H-chromen-2-one (6a)ꢀPale yellow solid; mp 175–177°C;
IR: 3034 (Ar-H), 1728 (C ꢀ= ꢀO of chalcone), 1598 (C ꢀ= ꢀC ), 1453 (N ꢀ= ꢀN ), 1169
1
FT-IR-8400s spectrophotometer. The H NMR spectra (400 MHz) and
-1
1
(
C-N), 1089 cm (Ar-O); H NMR: δ 2.41 (s, 3H, CH ), 5.32 (s, 2H, N-CH ),
1
3
3
2
C NMR spectra (100 MHz) were recorded in CDCl on a Bruker DPX
3
5
.38 (s, 2H, O-CH ), 6.15 (s, 1H, H ), 6.97 (d, 1H, H , J ꢀ= ꢀ 16 Hz), 7.13–7.15
2
3
α
4
00 spectrophotometer. The high-resolution electron spray ioniza-
(
m, 2H, Ar-H), 7.17 (d, 1H, H , J ꢀ= ꢀ 9 Hz), 7.22–7.47 (m, 10H, H , triazole
6
β
tion mass spectra (ESI-HR-MS) were recorded on a Micromass Q-Tof
1
3
H, Ar-H), 7.62 (d, 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR: δ 18.7, 54.2 (N-CH ), 63.2
5
2
(
ESI-HR-MS) mass spectrometer.
(
O-CH ), 109.4, 113.0, 114.6, 122.9, 125.6, 126.5, 127.9, 128.0, 128.03, 128.6,
2
1
28.81, 128.82, 128.9, 129.1, 130.9, 134.2, 134.3, 146.4, 151.9, 157.6, 159.8,
+
1
91.7 (C ꢀ= ꢀO , chalcone). ESI-HR-MS. Calcd for C H N O Na [M+Na] :
29
23
3
4
Synthesis of compounds 6a–i from substrates 5a–i
m/z 500.1586. Found: m/z 500.1588.
Conventional methodꢀA mixture of CuSO ·5H O (0.15 mmol), (E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-[3-(4-methoxy-
4
2
sodium ascorbate (0.15 mmol), benzyl azide (1.5 mmol), and (E)-8-(3- phenyl)acryloyl]-4-methyl-2H-chromen-2-one (6b)ꢀPale yellow
(
(
arylacryloyl)-4-methyl-7-(prop-2-yn-1-yloxy)-2H-chromen-2-one 5a–i solid; mp 205–207°C; IR: 3038 (Ar-H), 1731 (C ꢀ= ꢀO of chalcone), 1600
-1 1
1.5 mmol) in t-BuOH: H O (1:1, 5 mL) was stirred at room temperature (C ꢀ= ꢀC ), 1459 (N ꢀ= ꢀN ), 1173 (C-N), and 1097 cm (Ar-O). H NMR (400
2
for 24 h. Af er completion of the reaction, as monitored by TLC, the MHz, CDCl ) δ (ppm): 2.41 (s, 3H, CH ), 3.84 (s, 3H, OCH ), 5.32 (s,
3
3
3
mixture was poured onto ice-cold water (20 mL) and extracted with 2H, N-CH ), 5.39 (s, 2H, O-CH ), 6.15 (s, 1H, H ), 6.83–7.31 (m, 11H, H ,
2
2
3
α
EtOAc (30 mL). The extract was washed twice with saturated solution Ar-H, H ), 7.41 (d, 1H, H , J ꢀ= ꢀ 9 Hz), 7.45 (s, 1H, triazole H), 7.61 (d,
β
6
1
3
of NH Cl, twice with brine, dried over Na SO , and concentrated in 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR: δ 18.7, 54.2, 55.4, 63.2, 109.4, 113.0, 114.4,
4
2
4
5
vacuo. The residue was purified by column chromatography on silica 115.2, 122.8, 123.0, 125.9, 126.3,127.0, 127.9, 128.8, 129.0, 130.2, 130.43,
gel eluting with hexanes/EtOAc (3:1) to afford compound 6a–i.
146.5, 151.3, 156.0, 157.6, 159.9, 161.9, 166.4, 191.6. ESI-HR-MS. Calcd for
+
C H N O Na [M+Na] : m/z 530.1692. Found: m/z 530.1694.
3
0
25
3
5
Microwave irradiationꢀThe mixture indicated above was subjected
to MWI at 180 W for 8–10 min. Af er completion of the reaction, as (E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-[3-(3,4-dimeth-
monitored by TLC, the mixture was worked up and the product 6a–i oxyphenyl)acryloyl]-4-methyl-2H-chromen-2-one (6c)ꢀPale yel-
purified as described above.
low solid; mp 217–219°C; IR: 3040 (Ar-H), 1732 (C ꢀ= ꢀO of chalcone), 1605
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A. Dongamanti et al.: Triazole-coumarin hybridsꢂꢁꢀꢀꢀꢂ297
-
1
1
-1
1
(
C ꢀ= ꢀC ), 1463 (N ꢀ= ꢀN ), 1175 (C-N), and 1097 cm (Ar-O). H NMR: δ 2.42 (s, (C ꢀ= ꢀC ), 1459 (N ꢀ= ꢀN ), 1170 (C-N), and 1097 cm (Ar-O); H NMR: δ 2.41
3
H, -CH ), 3.81 (s, 3H, OCH ), 3.98 (s, 3H, OCH ), 5.32 (s, 2H, N-CH ), (s, 3H, CH ), 5.32 (s, 2H, N-CH ), 5.38 (s, 2H, O-CH ), 6.15 (s, 1H, H ),
3
3
3
2
3
2
2
3
5
7
.39 (s, 2H, N-CH ), 6.15 (s, 1H, H ), 6.82–6.91 (m, 2H, H , Ar-H), 7.13– 6.88 (d, 1H, H , J ꢀ= ꢀ 16 Hz), 6.95–6.98 (m, 2H, Ar-H), 7.04 (d, 1H, H , J ꢀ= ꢀ
2
3
α
α
6
.39 (m, 9H, H , Ar-H, H ), 7.47 (s, 1H, triazole H), 7.62 (d, 1H, H , J ꢀ= ꢀ 9 9 Hz), 7.07–7.44 (m, 8H, H , Ar-H), 7.47 (s, 1H, triazole H), 7.62 (d, 1H,
6
β
5
β
13
13
Hz); C-NMR: δ 18.7, 54.3, 56.4, 57.5, 63.2, 109.3, 113.7, 114.1, 115.6, 122.1, H , J ꢀ= ꢀ 9 Hz); C-NMR: δ 18.7, 54.3, 63.2, 109.3, 113.0, 114.5, 126.8, 127.0,
5
1
1
23.9, 125.2, 126.6, 127.1, 127.7, 128.5, 129.0, 130.2, 130.48, 146.4, 151.3, 127.2, 128.0, 128.3, 128.8, 129.1, 129.2, 129.5, 130.1, 130.2, 131.5, 134.2,
51.9, 152.6, 156.2, 157.6, 159.9, 161.9, 166.4, 191.6. ESI-HR-MS. Calcd for 135.1, 141.6, 142.1, 151.7, 151.9, 157.7, 159.8, 191.6; ESI-HR-MS. Calcd for
+
+
C H N O Na [M+Na] : m/z 560.1797. Found: m/z 560.1794.
C H ClN O Na [M+Na] : m/z 534.1196. Found: 534.1192.
31
27
3
6
29 22
3
4
(
(
E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-4-methyl-8-[3- (E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-4-methyl-8-[3-
3,4,5-trimethoxyphenyl)acryloyl]-2H-chromen-2-one(6d)ꢀPale (p-tolyl)acryloyl]-2H-chromen-2-one (6i)ꢀPale yellow solid; mp
yellow solid, mp: 221–223°C; IR: 3040 (Ar-H), 1731 (C ꢀ= ꢀO of chalcone), 170–172°C; IR: 3038 (Ar-H), 1731 (C ꢀ= ꢀO of chalcone), 1600 (C ꢀ= ꢀC ), 1459
-
1
1
-1
1
1
602 (C ꢀ= ꢀC ), 1460 (N ꢀ= ꢀN ), 1171 (C-N), and 1095 cm (Ar-O); H NMR: δ (N ꢀ= ꢀN ), 1173 (C-N), and 1095 cm (Ar-O); H NMR: δ 2.41 (s, 3H, CH ),
3
2
.42 (s, 3H, CH ), 3.82 (s, 9H, 3 ꢀ× ꢀ OCH ), 5.32 (s, 2H, N-CH ), 5.40 (s, 2H, 2.62 (s, 3H, Ar-CH ), 5.32 (s, 2H, N-CH ), 5.38 (s, 2H, O-CH ), 6.15 (s, 1H,
3
3
2
3
2
2
O-CH ), 6.16 (s, 1H, H ), 6.88 (d, 1H, H , J ꢀ= ꢀ 16 Hz), 7.17–7.35 (m, 9H, H , H ), 6.85 (d, 1H, H , J ꢀ= ꢀ 16 Hz), 7.05–7.36 (m, 10H, Ar-H, H ), 7.41 (d, 1H,
2
3
α
6
3
α
β
1
3
13
Ar-H, H ), 7.47 (s, 1H, triazole H), 7.62 (d, 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR: H , J ꢀ= ꢀ 9 Hz), 7.45 (s, 1H, triazole H), 7.61 (d, 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR:
β
5
6
5
δ 18.7, 54.2, 56.0, 56.2, 61.0, 63.2, 105.6, 109.4, 113.1, 114.5, 123.0, 126.4, δ 18.7, 29.7, 54.2, 63.2, 109.3, 113.0, 114.4, 122.9, 125.9, 126.3, 126.9, 127.9,
1
1
5
27.4,127.9, 128.0, 128.8, 129.0, 129.1, 129.7, 134.1, 146.5, 151.4, 151.8, 128.0, 128.4, 128.7, 129.0, 130.4, 143.7, 146.4, 151.3, 151.8, 156.0, 157.6,
+
+
53.4, 153.5, 157.6, 191.6. ESI-HR-MS. Calcd for C H N O Na [M+Na] : 159.4, 161.9, 191.6. ESI-HR-MS. Calcd for C H N O Na [M+Na] : m/z
32
29
3
7
30 25
3
4
90.1903. Found: m/z 530.1900.
514.1742. Found: m/z 514.1725.
(
E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-[3-(4-fluoro-
phenyl)acryloyl]-4-methyl-2H-chromen-2-one (6e)ꢀPale yellow
solid, mp: 185–187°C; IR: 3039 (Ar-H), 1731 (C ꢀ= ꢀO of chalcone), 1600
Biological activities
-1
1
(
C ꢀ= ꢀC ), 1460 (N ꢀ= ꢀN ), 1173 (C-N), and 1097 cm (Ar-O). H NMR: δ 2.41
(
s, 3H, CH ), 5.32 (s, 2H, N-CH ), 5.38 (s, 2H, O-CH ), 6.17 (s, 1H, H ), All synthesized compounds were screened for their antimicrobial
3
2
2
3
6
.88 (d, 1H, H , J ꢀ= ꢀ 16 Hz), 6.95–6.98 (m, 2H, Ar-H), 7.04 (d, 1H, H , activity against two strains of Gram-positive bacteria (Staphylococ-
α
6
J ꢀ= ꢀ 9 Hz), 7.07–7.44 (m, 8H, H , Ar-H), 7.47 (s, 1H, triazole H), 7.62 (d, cus aureus and Bacillus subtilis), two strains of Gram-negative bac-
β
1
3
1
1
1
H, H , J ꢀ= ꢀ 9 Hz); C-NMR: δ 18.7, 54.2, 63.2, 109.4, 113.0, 114.6, 116.0, teria (Echerichia coli and Pseudomonas aeruginosa), as well as three
5
16.2, 126.4, 126.5,127.9, 128.0, 128.1, 128.7, 128.8, 129.12, 129.19, 130.5, strains of fungi (Aspergillus niger, Penicillium italicum, and Fusarium
30.56, 130.6, 134.2, 145.1, 151.4, 152.0, 157.7, 191.7; ESI-HR-MS. Calcd oxysporum). Standard antibiotic drugs amoxicillin for bacteria and
+
for C H FN O Na [M+Na] : m/z 518.1492. Found: m/z 518.1490.
mycostatin for fungi were used at a concentration of 50 μg/mL for
comparison. The biological activities of these compounds were eval-
2
9
22
3
4
(
E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-[3-(4-dimethyl- uated by the filter paper disc method [18] for 50 μg/mL solutions in
aminophenyl)acryloyl]-4-methyl-2H-chromen-2-one (6f)ꢀPale DMF. The inhibition zones of microbial growth surrounding the fil-
yellow solid; mp 198–200°C IR: 3038 (Ar-H), 1732 (C ꢀ= ꢀO of chalcone), ter paper disc (5 mm) were measured in millimeters at the end of an
-1
1
1
600 (C ꢀ= ꢀC ), 1459 (N ꢀ= ꢀN ), 1172 (C-N), and 1097 cm (Ar-O); H NMR: δ incubation period of 3 days at 37°C for E. coli and at 28°C for other
.41 (s, 3H, CH ), 2.54 (s, 6H, 2 ꢀ× ꢀ CH ), 5.31 (s, 2H, N-CH ), 5.52 (s, 2H, bacteria and fungi; DMF alone showed no inhibition zone.
2
3
3
2
O-CH ), 6.16 (s, 1H, H ), 6.63–7.31 (m, 11H, H , Ar-H, H ), 7.40 (d, 1H,
2
3
α
β
1
3
H , J ꢀ= ꢀ 9 Hz), 7.47 (s, 1H, triazole H), 7.74 (d, 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR:
δ 18.7, 32.4, 54.3, 63.2, 109.3, 111.0, 111.7, 112.9, 114.4, 120.0, 122.1, 122.8,
6
5
Acknowledgments: The authors are thankful to the head
1
1
5
24.8, 126.4, 128.0, 128.1, 128.9, 129.0, 133.4, 152.0, 154.5, 156.9, 159.7, of the Department of Chemistry, Osmania University,
+
62.3, 166.5 199.2. ESI-HR-MS. Calcd for C H N O Na [M+Na] : m/z
3
1
28
4
4
Hyderabad, India, for providing laboratory facilities and
to the director of CFRD, Osmania University, Hyderabad,
India, for providing spectral analysis facilities. One of the
authors, B.V.L., is thankful to CSIR, New Delhi, India, for
43.2008. Found: m/z 543.2010.
(
E)-7-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy]-8-[3-(4-isopro-
pylphenyl)acryloyl]-4-methyl-2H-chromen-2-one (6g)ꢀPale
yellow solid; mp 165–167°C IR: 3035 (Ar-H), 1729 (C ꢀ= ꢀO of chalcone), financial support in the form of CSIR-SRF.
-
1
1
1
1
598 (C ꢀ= ꢀC ), 1448 (N ꢀ= ꢀN ), 1163 (C-N), and 1088 cm (Ar-O); H NMR: δ
.2 (s, 6H, (CH ) ), 2.41 (s, 3H, CH ), 2.6 (m, 1H, CH(Me) ), 5.32 (s, 2H,
3
2
3
2
N-CH ), 5.38 (s, 2H, O-CH ), 6.14 (s, 1H, H ), 6.95 (d, 1H, H , J ꢀ= ꢀ 16 Hz),
2
2
3
α
References
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.12–7.14 (m, 2H, Ar-H), 7.17 (d, 1H, H , J ꢀ= ꢀ 9 Hz), 7.24–7.44 (m, 8H, H ,
6
β
13
Ar-H), 7.47 (s, 1H, triazole H), 7.62 (d, 1H, H , J ꢀ= ꢀ 9 Hz); C-NMR: δ 18.7,
5
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29
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