Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological Potent Molecules

Article abstract of DOI:10.1002/jhet.3187

A series of novel 5-((1H-benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-2,2-dimethyl-6-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-phenylthiazolidin-4-ones 9a–n has been synthesized from triazole-linked thiazolidinone derivatives 8a–g with o-phenylenediamine and characterized by IR, NMR, MS, and elemental analyses. Further, these compounds were screened for their antibacterial activity against Gram-positive bacteria, namely, Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), and Micrococcus luteus (IFC 12708), and Gram-negative bacteria, namely, Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), and Escherichia coli (ATCC 25922). Among the screened compounds, compounds 9b, 9d, 9h, and 9i are highly active against almost all selected bacterial strains; the remaining compounds showed moderate to good activity and emerged as potential molecules for further development.

Full text of DOI:10.1002/jhet.3187

Month 2018
Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological
Potent Molecules
A. Srinivas,a*
a
b
a
a
M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
a
Department of Chemistry, Vaagdevi Degree & PG College, Kishanpura, Warangal, Telangana 506001, India
Department of Zoology, Vaagdevi Degree & PG College, Kishanpura, Warangal, Telangana 506001, India
b
*
E-mail: avula.sathwikreddy@gmail.com
Received December 23, 2017
DOI 10.1002/jhet.3187
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel 5-((1H-benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-2,2-dimethyl-6-((1-phenyl-
H-1,2,3-triazol-4-yl)methoxy)tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-phenylthiazolidin-4-ones 9a–n has
1
been synthesized from triazole-linked thiazolidinone derivatives 8a–g with o-phenylenediamine and
characterized by IR, NMR, MS, and elemental analyses. Further, these compounds were screened for their
antibacterial activity against Gram-positive bacteria, namely, Bacillus subtilis (ATCC 6633), Staphylococcus
aureus (ATCC 6538p), and Micrococcus luteus (IFC 12708), and Gram-negative bacteria, namely, Proteus
vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), and Escherichia coli (ATCC 25922).
Among the screened compounds, compounds 9b, 9d, 9h, and 9i are highly active against almost all selected
bacterial strains; the remaining compounds showed moderate to good activity and emerged as potential
molecules for further development.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
,2,3-Triazoles are one of the most important classes of
Thiazoles are familiar group of heterocyclic compounds
possessing a wide variety of biological activities, and their
utility as medicine is very much established [6]. Thiazole
nucleus is also an integral part of all the available
penicillins, which have revolutionized the therapy of
bacterial diseases [7]. Further, the chemistry of
thiazolidinone ring system is one considerable interest as
its core structure in various synthetic pharmaceuticals
displaying a broad spectrum of biological activities [8].
The thiazolidinone nucleus also appears frequently in the
structure of various natural products notably thiamine,
compounds possessing cardiac and glycemic benefits
such as troglitazone [9], and many metabolic products of
fungi and primitive marine animals, including
2-(aminoalyl)-thiazole-4-carboxylic acids [10]. Numerous
thiazolidinone derivatives have shown significant
bioactivities such as antidiarrheal [11], anticonvulsant
[12], antimicrobial [13], antidiabetic [14], antihistaminic
[15], anticancer [16], anti-human immunodeficiency virus
1
heterocyclic organic compounds, which are reported to be
present in a plethora of biological activities for diverse
therapeutic areas [1]. The 1,2,3-triazole motif is
associated with diverse pharmacological activities such as
antibacterial, antifungal, hypoglycemic, antihypertensive,
and analgesic properties. Polysubstituted five-membered
aza-heterocyclics rank the most potent glycosidase
inhibitors [2]. Further, this nucleus in combination with
or in linking with various other classes of compounds
such as amino acids, steroids, aromatic compounds,
carbohydrates, and so forth became prominent in having
various pharmacological properties [3]. 1,2,3-Triazole-
modified carbohydrates have became easily available
after the discovery of the Cu(I) catalyzed azide-alkynes
1
,3-dipolar cycloaddition reaction [4] and quickly became
a prominent class of non-natural sugars. The chemistry
and biology of triazole-modified sugars are dominated by
triazole glycosides [5]. Therefore, the synthesis and
investigation of biological activity of 1,2,3-triazole
glycosides is an important objective, which also received
considerable attention from medicinal chemists.
+2
[17], Ca channel blocker [18], platelet-activating factor
antagonist [19], cardioprotective [20], antiischemic [21],
COX inhibitory [22], antiplatelet-activating factor [23],
non-peptide thrombin receptor antagonist [24], tumor
necrosis factor-α antagonist [25], and nematicidal
©
2018 Wiley Periodicals, Inc.

A. Srinivas, M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
Vol 000
activities. Natural biological substances such as purine
RESULTS AND DISCUSSION
bases and vitamin B12 include benzimidazole moiety in
their structure. Several benzimidazole derivatives are
reported to exhibit antimicrobial [26–28], anticancer
The key intermediate 8 required for the synthesis of title
compound was prepared according to the procedure
outlined in the Scheme 1. Diacetone D-glucose (1)
prepared from D(+)-glucose by treating with acetone in
the presence of catalytic amount of sulfuric acid according
to the literature procedure [47], reduction of 2 prepared by
[
[
29,30], antifungal [31,32], antiparasitic [33], antiviral
34], anti-inflammatory [35], and antihistaminic [36]
activities.
Microwave irradiation is an alternative heating
technique based on the transformation of electromagnetic
energy into heat. Often this method increases the rate of
chemical reactions [37] and results in higher yields.
Microwave energy couples directly with polar molecules
or ions and leads to a rapid rise in the temperature of
reaction medium [38,39]. Reactions that require hours or
even days using conventional heating can usually be
completed in minutes or seconds using microwaves.
Several reactions have been performed under microwave-
assisted conditions with significant rate enhancements,
improved yield, and selectivity [39].
Following the successful introduction of antimicrobial
agent microwave-assisted synthesis, inspired by the
biological profile of triazoles, thiazolidinones, and
benzimidazoles, and in the continuation of our work on
biological active molecules [40–46], we have developed a
series of novel hybrid heterocyclics and investigated the
application of microwave irradiation for the synthesis of
our hybrid molecules and evaluated their antimicrobial
activity.
Swern oxidation of 1, with NaBH in aq ethanol at 0°C
4
for 1 h gave 3 (77%), which on subsequent propargylation
in dimethylformamide (DMF) in the presence of NaH for
1 h afforded propargyl ether 4 (80%). Now, the propargyl
ether converted into triazole 5 (82%) by using 1,3-dipolar
cycloaddition with p-chlorophenyl azide was carried out
at ambient temperature in the presence of CuSO and
4
sodium ascorbate in a mixture of 1:1 t-BuOH–H O as
2
reported by Sharpless. Acid hydrolysis of 5,6-acetonide 5
in 60% AcOH furnished the diol 6 (85%), which on
oxidative cleavage with NaIO4 gave the aldehyde 7.
Subsequently, one-pot synthesis of triazole-linked
thiazolidinone glycosides was carried out by the
condensation reaction between 7, primary aromatic
amine, and a thiomalic acid in the presence of ZnCl2
under microwave irradiation/conventional heating
(Scheme 2). Compound 8 on further condensation with
o-phenelene diamine in presence of acid yielded
compound 9. In classical method, the reactions were
performed in dry toluene and DMF at reflux for a long
Scheme 1. Synthesis of compound 7.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological
Potent Molecules
Scheme 2. Synthesis of compound 9a-n.
time (2–4 h), often leading to degradation processes and
consequent low yields of isolated products, whereas in
the application of microwave-assisted technology, the
reaction is completed in only 5–10 min, and the
compounds, isolated by conventional workup, are
obtained in satisfactory yields, often higher than those
achieved by traditional methods. The structures of
synthesized compounds were confirmed by IR, NMR,
MS, and elemental analysis. In the IR spectrum of
luteus (IFC 12708), and Gram-negative bacteria, namely,
Proteus vulgaris (ATCC 3851), Salmonella typhimurium
(ATCC 14028), and Escherichia coli (ATCC 25922) by
the broth dilution method, recommended by the National
Committee for Clinical Laboratory Standards [48]. The
bacteria were grown overnight in Luria–Bertani broth at
37°C, harvested by centrifugation, and then washed twice
with sterile distilled water. Stock solutions of the series of
compounds were prepared in DMSO. Each stock solution
was diluted with standard method broth (Difco) to
prepare serial twofold dilutions in the range of 50 to
0.8 μg/mL. Ten microliters of the broth containing about
compound 9a, disappearance of carboxylic acid
À1
carbonyl (C═O) absorption band at about 1710 cm
,
which was present in compound 8a, confirmed the
cyclization of involvement of carboxylic acid system. In
addition, the absorption bands corresponding to –N–H
of the benzimidazole moiety and –N═N– of the triazole
5
10 cfu/mL of test bacteria was added to each well of 96-
well microtiter plate. Culture plates were incubated for
24 h at 37°C, and the growth was monitored visually and
spectrophotometrically. The lowest concentration required
to arrest the growth of bacteria was regarded as minimum
inhibitory concentration (μg/mL), was determined for all
the compounds, and was compared with the control.
Amphicillin was also screened under identical conditions
for comparison. Data of the compounds 9a–n are
presented in Table 1 as the minimum inhibitory
concentration. Among the screened compounds 9a–n, the
imidazole moiety-bearing electron-withdrawing group on
the fourth position of phenyl, namely, 4-chlorophenyl 9b,
is highly active against all the microorganisms employed
(at 1.56 μg/mL) (except E. coli); it is almost equal to the
standard. Compound 9d, bearing electron-withdrawing
group on the fourth position of phenyl, namely, 4-
chlorophenyl, is also highly active but only against
À1
1
were observed at 3414 and 1610 cm . In H-NMR
spectrum, the –NH proton of benzimidazole ring
appeared at 9.32 ppm as a singlet, and four aromatic
hydrogens of benzimidazole appeared as doublets at
7
.44 and 7.21. These signals demonstrate that the
1
3
cyclization step has occurred. In C-NMR spectra, the
prominent signals corresponding to the carbons of
benzimidazole in compound 9a observed at 151.4,
138.9, and 33.2 ppm are proof of their structure.
Further, the compounds were subject to antibacterial
testing.
Antibacterial activity. All the compounds 9a–n were
assayed for their antibacterial activity against Gram-
positive bacteria, namely, Bacillus subtilis (ATCC 6633),
Staphylococcus aureus (ATCC 6538p), and Micrococcus
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Srinivas, M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
Vol 000
Table 1
Antimicrobial activity of the synthesized compounds.
MIC (μg/mL)
Bacillus
subtilis
Escherichia
coli
Compound
Staphylococcus aureus
Micrococcus luteus
Proteus vulgaris
Salmonella typhimurium
9
a
12.5
6.25
1.56
6.25
3.12
12.5
6.25
12.5
6.25
15.7
25.0
20.7
24.5
1.56
25.0
12.5
6.25
6.25
1.56
12.5
25.0
25.0
12.5
19.6
20.0
18.5
22.0
12.5
12.5
12.5
1.56
6.25
12.5
6.5
25.0
12.5
1.25
17.0
22.8
20.4
23.6
1.56
25.0
12.5
1.56
6.25
1.56
3.12
25.0
1.56
11.5
0
12.5
6.25
1.56
12.5
1.56
12.5
6.25
1.56
1.25
17.9
19.6
22.8
25.0
3.12
25.0
12.5
1.56
25.0
3.12
6.25
50.0
12.5
10.5
18.5
25.0
21.5
22.0
3.12
9b
9
c
9d
9
9
e
f
9g
9
9
h
9
k
i
9
l
19.2
15.7
24.7
1.56
9m
9n
Ampicillin
MIC, minimum inhibitory concentration.
M. luteus and P. vulgaris at the same concentration as 9h.
Compound 9i, bearing electron-withdrawing group on the
fourth position of phenyl, namely, 4-chlorophenyl, also
showed good antibacterial activity against B. subtilis,
S. aureus, M. luteus, and S. typhimurium. The remaining
compounds showed moderate to good activity.
spectrometer. Elemental analyses (C, H, and N)
determined by a PerkinElmer 240 CHN elemental
analyzer were within ±0.4% of theoretical.
(
3aR,5R,6aS)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2,2-
dimethyldihydrofuro[3,2-d][1,3]dioxol-6-(3aH)-one (2).
Oxolylchlorode of 8.5 mL was dissolved in 20 mL of
dry CH Cl and cooled to À78°C, and 14 mL of DMSO
2
2
was added to a solution of 5 g of alcohol 1 in 30 mL of
EXPERIMENTAL
CH Cl . The reaction mixture was stirred for 45 min,
2
2
quenched with 40 mL Et N, and warmed to 25°C. The
3
Commercial grade reagents were used as supplied.
Solvents except analytical reagent grade were dried and
purified according to literature when necessary. Reaction
progress and purity of the compounds were checked by
thin-layer chromatography (TLC) on precoated silica gel
F254 plates from Merck (Merck, Bangalore, India), and
compounds were visualized either by exposing to UV
light or by dipping in 1% aq potassium permanganate
solution. Silica gel chromatographic columns (60–120
mesh) were used for separations. Optical rotations were
measured on a PerkinElmer 141 polarimeter (Perkin
Elmer, Waltham, MA) by using a 2-mL cell with a path
length of 1 dm with CHCl3 or CDCl3 as solvent.
Microwave reactions are carried out in minilab microwave
catalytic reactor (ZZKD, WBFY-201), and reaction
mixture temperatures were measured through an immersed
fiber optic sensor. All melting points are uncorrected and
measured using Fisher–Johns apparatus. IR spectra were
recorded as KBr disks on a PerkinElmer FT IR
reaction mixture was extracted with CH Cl , and organic
2
2
layer separated was washed with water (50 mL) and
brine (50 mL), dried (Na SO ), and evaporated. Residue
2
4
obtained was purified by column chromatography
(60–120 mesh silica gel, 10% ethyl acetate in petroleum
ether) to afford 2 as quantitative yield (4.5 g, 87%) as a
yellow syrup, which was used as such for the next
reaction.
(
3aR,5S,6R,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-
2,2-dimethyltetrahydrofuro[3,2-d][1,3]dioxol-6-ol (3).
To a
stirred solution of 2 (4.5 g, 19 mmol) in aq ethanol
(EtOH : H O19: 1; 100 mL), NaBH (0.37 g, 9.7 mmol)
2
4
was added at 0°C, and then reaction mixture was stirred
for1 h. Solvent was evaporated in vacuum, residue
treated with saturated NH Cl solution (10 mL), and
4
stirred at room temperature for an additional 10 min. The
reaction mixture was extracted with EtOAc (2 × 50 mL),
and organic layer separated was washed with water
(50 mL) and brine (50 mL), dried (Na SO ), and
2
4
1
13
spectrometer. The H-NMR and C-NMR spectra were
recorded on a Varian Gemini spectrometer (300 MHz for
evaporated. Residue obtained was purified by column
chromatography (60–120 mesh silica gel, 60% ethyl
acetate in petroleum ether) to afford 3 (3.8 g, 80%) as a
1
13
H and 75 MHz for C). Chemical shifts are reported as δ
2
0
ppm against tetramethylsilane as internal reference, and
coupling constants (J) are reported in Hertz units. Mass
spectra were recorded on a VG micro mass 7070H
white solid; mp 82°C; [α] + 82.49 (c 1.62, CHCl3);
D
1
H-NMR (300 MHz, CDCl , 298 K): δ 5.75 (d, 1H,
3
J = 3.7 Hz, C H), 4.56 (d, 1H, J = 4.2 Hz, C H), 4.23
1
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological
Potent Molecules
+
(
m, 1H, C H), 4.07–3.91 (m, 3H, C H, 2 × C H), 3.74 (dd,
26.6, 26.2, 24.9. MS: m/z (M + H) 452. Anal. Calcd
5
4
6
1
1
2
1
H, J = 8.0, 4.3 Hz, C H), 2.44 (d, 1H, J = 8.4 Hz, OH),
for C H ClN O : C, 55.81; H, 5.80; N, 9.30. Found:
C, 55.75; H, 5.75; N, 9.21.
3
21 26
3 6
.56 (s, 3H, CH ), 1.44 (s, 3H, CH ), 1.36 (s, 6H,
3
3
13
× CH3); C-NMR (75 MHz, CDCl ): δ 112.8, 109.8,
3
(
R)-1-((3aR,5R,6R,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[3,2-d][1,3]
dioxol-5-yl)ethane-1,2-diol (6).
03.9, 79.7, 79.0, 75.5, 72.5, 65.8, 26.6, 26.5, 26.3, 25.3;
+
MS: m/z (M + Na) 283.
A mixture of 5 (3 g,
(
3aR,5R,6R,6aR)-5-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-
6.65 mmol) in 60% aq AcOH (25 mL) was stirred at
room temperature for 12 h. Reaction mixture was
neutralized with anhyd NaHCO3 (15 g) and extracted
with EtOAc (3 × 40 mL). The combined organic layers
were dried (Na SO ), evaporated, and residue purified by
2
,2-dimethyl-6-(prop-2-ynyloxy)tetrahydrofuro[3,2-d][1,3]
dioxole (4). Sodium hydride (60% in mineral oil, 0.64 g)
was added to a stirred solution of 3 (3.6 g, 13.84 mmol) in
DMF (80 mL) at 0°C and stirred for 30 min. This yellow
mixture was cooled to 0°C and treated with propargyl
bromide (4.2 g) in DMF (20 mL). The dark brown
reaction mixture was stirred for an hour at room
temperature and quenched (at 5–10°C) with saturated aq
ammonium chloride (20 mL). The crude product was
extracted with methylene chloride (3 × 30 mL), dried
2
4
column chromatography (60–120 mesh silica gel, 41%
ethyl acetate in petroleum ether) to afford 6 (2.6 g, 82%)
1
as a pale yellow solid; mp 168–171°C. HNMR
(
300 MHz, CDCl ): δ 8.03 (s, 1H, Ar–H), 7.54 (d,
3
J = 9.2 Hz, 2H, Ar–H), 7.43 (d, J = 8.9 Hz, 2H, Ar–H),
.51 (d, J = 3.7 Hz, 1H, C H), 4.56 (t, J = 3.9 Hz, 1H,
5
1
(
Na SO ), and concentrated. The residue was purified by
column chromatography on silica gel (5% ethyl
acetate : hexane) to afford 4 (3.1 g, 75%). Viscous oil [α]
2 4
C H), 4.59 (s, 2H, OCH ), 3.98–3.93 (m, 2H, C H,
2 2 4
C H), 4.01–3.92 (m, 3H, C H, 2 × C H), 2.44 (bs, 1H,
5
3
6
OH), 1.54 (s, 3H, CH ), 1.50 (bs, 1H, OH), 1.34 (s, 3H,
3
1
13
À 6.3 (c 1.7, CHCl ). HNMR (300 MHz, CDCl ): δ
D
3
3
CH3); C-NMR (75 MHz, CDCl ): δ144.2, 134.2, 122.1,
3
5
.62 (d, J = 3.7 Hz, 1H, C H), 4.69 (t, J = 3.9 Hz, 1H,
1
119.2, 112.2, 109.2, 103.1, 79.8, 77.1, 74.1, 67.2, 66.2,
+
C H), 4.36 (dt, J = 3.1, 7.3 Hz, 1H, C H), 4.21 (s, 2H,
2
5
64.2, 70.6, 26.6, 26.2, 24.9. MS: m/z (M + H) 412.
CH ), 4.09–3.96 (m, 3H, C H, 2X C H), 3.68 (dd,
J = 8.9, 4.1 Hz, 1H, C H), 3.19 (s, 1H, CH), 1.56 (s, 3H,
CH ), 1.42 (s, 3H, CH ), 1.36 (s, 6H, 2 × CH );
C-NMR (75 MHz, CDCl ): δ 112.7, 109.5, 103.8, 80.2,
2
4
6
Anal. Calcd for C H ClN O : C, 52.49; H, 5.38; N,
18
22
3 6
3
10.21. Found: C, 52.35; H, 5.25; N, 10.11.
3
3
3
2
-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-
-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-
yl)-3-phenylthiazolidin-4-one (8a–g). To a solution of diol 6
0.200 g, 0.48 mmol) in CH Cl (5 mL), NaIO (0.130 g,
1
3
3
4
7
(
7.6, 77.2, 74.6, 66.2, 57.2, 26.6, 26.2. MS: m/z
+
M + Na) 321.
(
2
2
4
1
-(4-Chlorophenyl)-4-(((3aR,5R,6R,6aR)-5-((R)-2,2-
dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[3,2-d]
1,3]dioxol-6-yloxy)methyl)-1H-1,2,3-triazole (5). a
0.61 mmol) was added at 0°C and stirred at room
temperature for 6 h. The reaction mixture was filtered and
washed with CH Cl (2 × 10mL). It was dried (Na SO )
and evaporated to give aldehyde 7 (150 g) in quantitative
yield as a yellow liquid, which was used as such for the
next reaction. To a stirred mixture of 7 (0.150 g,
0.395 mmol), aromatic amine (0.395 mmol) and
thiomalic acid (0.125 g, 0.86 mmol) in dry toluene
[
To
2
2
2
4
solution containing (3 g, 10.06 mmol) the alkyne 4
p-chlorophenyl azide (1.8 g, 11.76 mmol) in
dichloromethane (30 mL) and water (30 mL) were
added CuSO 5H O (1.8 g, 8.15 mmol) and sodium
4
˙
2
ascorbate (1.2 g). The resulting suspension was stirred
at room temperature for 4–6 h. After this time, the
mixture was diluted with 20 mL dichloromethane and
(
5 mL), anhyd ZnCl (0.100 g, 0.751 mmol) was added
2
after 2 min and irradiated in microwave bath reactor at
80 W for 4–7 min at 110°C. After cooling, the filtrate
2
0 mL water. The organic phase was separated, dried
2
with sodium sulfate, and concentrated at reduced
pressure, and the crude residue was purified by column
chromatography silica gel (60–120 mesh, 35% EtOAc
was concentrated to dryness under reduced pressure, and
the residue was taken up in ethyl acetate. The ethyl
acetate layer was washed with 5% sodium bicarbonate
solution and finally with brine. The organic layer was
dried over Na SO and evaporated to dryness at reduced
in hexane) to afford 5 (3.2 g, 75%) as a white powder
1
mp 159–161°C. [α]D À 91.3 (c 1.7, CHCl ). HNMR
3
2
4
(
300 MHz, CDCl ): δ 8.05 (s, 1H, Ar–H), 7.56 (d,
3
pressure. The crude product thus obtained was purified
by column chromatography on silica gel (60–120 mesh)
with hexane–ethyl acetate as eluent. Under conventional
method, the reaction mixture in toluene (10 mL) was
refluxed at 110°C for the appropriate time (Table 2).
J = 9.2 Hz, 2H, Ar–H), 7.45 (d, J = 8.9 Hz, 2H,
Ar–H), 5.59 (d, J = 3.7 Hz, 1H, C H), 4.65 (t,
J = 3.9 Hz, 1H, C H), 4.59 (s, 2H, CH ), 4.39 (dt,
J = 3.1, 7.3 Hz, 1H, C H), 4.09–3.96 (m, 3H, C H,
× C H), 3.71 (dd, J = 8.9, 4.1 Hz, 1H, C H), 1.54 (s,
H, CH ), 1.40 (s, 3H, CH ), 1.34 (s, 6H, 2 × CH );
C-NMR (75 MHz, CDCl ): δ 144.1, 134.5, 122.4,
19.5, 112.5, 109.6, 103.6, 80.0, 77.4, 74.2, 67.5, 66.2,
1
2
2
5
4
2
6
3
2
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
3
3
3
3
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
1
3
3
dioxol-5-yl)-4-oxo-3-phenylthiazolidin-5-yl)acetic acid (8a).
1
1
mp 211–214°C. HNMR (300 MHz, CDCl ): δ 11.44 (s,
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Srinivas, M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
Vol 000
Table 2
Synthesis of compounds 8a–g and 9a–n.
Reaction time
Yield
1
Compound
R
R
Molecular formula
27ClN
A (h)
B (min)
A
B
8
8
8
8
8
8
8
9
9
9
9
9
9
9
9
9
9
9
9
9
9
a
b
c
d
e
f
g
a
b
c
d
e
f
g
h
i
j
k
l
C
6
H
5
—
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
27
H
27
H
27
H
28
H
28
H
27
H
27
H
33
H
30
H
33
H
33
H
33
H
33
H
34
H
34
H
34
H
34
H
33
H
33
H
33
H
33
H
4
O
7
S
3.5
2.5
3.0
2.5
2.0
3.0
2.5
4.5
3.0
4.0
4.5
4.2
4.0
5.0
4.5
4.1
3.6
4.1
3.9
3.9
3.7
5
6
7
5
5
5
4
8
4
2
2
4
3
25
10
9
5
8
63
65
61
70
67
77
79
65
63
70
68
68
72
69
70
65
75
69
65
71
68
79
82
79
81
82
87
90
85
76
88
81
85
90
87
85
91
92
88
89
85
88
4-Cl–C
4-NO
2-CH
4-CH
6
H
4
—
—
—
—
—
—
H
Cl
H
Cl
H
Cl
H
Cl
H
Cl
H
Cl
H
26Cl
26Cl
2
N
N
4
O
O
7
S
S
2
–C
6
H
4
2
5
9
3
ÀC
6
H
4
29ClN
29ClN
27ClN
27ClN
31ClN
4
4
4
4
6
O
O
O
O
O
7
7
8
8
5
S
S
S
S
S
3
–C
6
H
H
H
4
3-OH–C
4-OH–C
6
6
4
4
C
C
6
H
H
5
5
6
30Cl
30Cl
29Cl
2
2
3
N
6
N
6
N
6
O
5
O
5
O
5
S
S
S
4-Cl–C
4-Cl–C
4-NO
4-NO
2-CH
2-CH
4-CH
4-CH
3-OH
3-OH
4-OH
4-OH
6
H
H
4
4
6
2
–C
–C
6
6
H
H
4
30ClN
29Cl
33ClN
32Cl
33ClN
32Cl
31ClN
30Cl
31ClN
30Cl
7
O
7
S
2
4
2
N
7
O
7
S
3
3
3
3
ÀC
6
H
4
4
6
O
5
S
ÀC
6
H
2
N
6
O
5
S
–C
–C
6
H
H
4
6
O
5
S
6
4
2
N
6
O
5
S
6
O
6
S
2
N
6
O
6
S
6
9
8
m
n
6
O
6
S
Cl
2
N
6
O
6
S
A, conventional heating; B, microwave irradiation.
1
H, CO H), 8.09 (s, 1H, Ar–H), 7.55 (d, J = 9.2 Hz, 2H,
dioxol-5-yl)-3-(4-nitrophenyl)-4-oxothiazolidin-5-yl)acetic acid
2
1
Ar–H), 7.48 (d, J = 8.9 Hz, 2H, Ar–H), 6.73–7.35 (m,
H, Ar–H), 6.15 (s, 1H, CHS), 5.73 (d, J = 4.2 Hz, 1H,
C H), 4.69 (t, J = 3.9 Hz, 1H, C H), 4.65 (t, 1H, CH),
(8c).
mp 256–258°C. HNMR (300 MHz, CDCl
11.45 (s, 1H, CO H), 8.21 (d, J = 8.4 Hz, 2H), 8.01 (s,
H, Ar–H), 7.49 (d, J = 9.1 Hz, 2H, Ar–H), 7.41 (d,
J = 8.5 Hz, 2H, Ar–H), 6.79 (d, J = 9.6 Hz, 2H, Ar–H),
6.14 (s, 1H, CHS), 5.69 (d, J = 4.2 Hz, 1H, C H), 4.65
3
): δ
5
2
1
1
2
4.52 (s, 2H, OCH ), 3.92–3.89 (m, 1H, C H), 3.31 (dd,
2 4
J = 9.1, 4.2 Hz, 1H, C H), 2.38 (d, 2H, CH ), 1.53 (s,
1
3
2
1
3
(
t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C H), 4.52 (s, 2H,
3H, CH ), 1.30 (m, 3H, CH ); C-NMR (75 MHz,
2
3
3
CDCl ): δ 170.9, 143.8, 141.2, 134.2, 128.2, 126.8,
OCH
4.2 Hz, 1H, C
2
), 3.90–3.86 (m, 1H, C
4
H), 3.19 (dd, J = 9.1,
3
1
22.1, 118.8, 104.2, 80.4, 77.9, 73.8, 66.1, 52.0, 37.2,
3
H), 2.30 (d, 2H, CH
), 1.49 (s, 3H, CH
2
),
3
+
13
1
.25 (m, 3H, CH3);
C-NMR (75 MHz, CDCl ): δ
33.9, 25.9; MS: m/z (M + H) 545. Anal. Calcd for
3
C H ClN O S: C, 55.24; H, 4.64; N, 9.54. Found: C,
190.2, 173.2, 143.6, 141.9, 134.5, 128.2, 126.5, 122.2,
118.2, 104.3, 80.4, 77.2, 73.1, 66.2, 52.1, 36.4, 33.1,
25.4; MS: m/z (M + H) 632. Anal. Calcd for
2
7
27
4 7
5
5.12; H, 4.59; N, 9.39.
+
2
-(3-(4-Chlorophenyl)-2-((3aR,5S,6S,6aR)-6-((1-(4-
chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-4-
C H Cl N O S: C, 51.31; H, 4.15; N, 11.08. Found: C,
27
26
2 5 9
5
1.19; H, 4.09; N, 10.95.
oxothiazolidin-5-yl)acetic acid (8b).
mp 259–261°C.
2
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
1
HNMR (300 MHz, CDCl ): δ 11.44 (s, 1H, CO H),
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
3
2
7
(
.98 (s, 1H, Ar–H), 7.45 (d, J = 9.2 Hz, 4H, Ar–H), 7.39
d, J = 8.9 Hz, 4H, Ar–H), 6.14 (s, 1H, CHS), 5.73 (d,
J = 4.2 Hz, 1H, C H), 4.69 (t, J = 3.9 Hz, 1H, C H),
dioxol-5-yl)-4-oxo-3-o-tolylthiazolidin-5-yl)acetic acid (8d).
1
mp 247–249°C. HNMR (300 MHz, CDCl ): δ 11.45
3
(s, 1H, CO H), 8.22 (d, J = 8.4 Hz, 2H, Ar–H), 8.06
1
2
2
4
.65 (t, 1H, CH), 4.52 (s, 2H, OCH ), 3.92–3.89 (m, 1H,
(s, 1H, Ar–H), 7.50 (d, J = 9.1 Hz, 2H, Ar–H), 7.42–
6.85 (m, 4H, Ar–H), 6.14 (s, 1H, CHS), 5.65 (d,
2
C H), 3.20 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.34 (d, 2H,
CH ), 1.53 (s, 3H, CH ), 1.30 (m, 3H, CH ); C-NMR
4
3
1
3
J = 4.2 Hz, 1H, C H), 4.60 (t, 1H, CH), 4.53 (t,
2
3
3
1
(
75 MHz, CDCl ): δ 170.6, 143.2, 141.6, 134.6, 128.8,
J = 3.9 Hz, 1H, C H), 4.54 (s, 2H, OCH ), 3.92–3.86
3
2
2
1
26.9, 122.2, 118.4, 104.5, 80.6, 77.6, 73.2, 66.4, 52.3,
(m, 1H, C H), 3.22 (dd, J = 9.1, 4.2 Hz, 1H, C H),
4
3
+
36.9, 33.2, 25.6; MS: m/z (M + H) 621. Anal. Calcd for
2.34 (d, 2H, CH ), 2.21 (s, 3H, CH ), 1.51 (s, 3H,
2 3
13
C H Cl N O S: C, 52.18; H, 4.22; N, 9.01. Found: C,
CH ), 1.29 (m, 3H, CH ); C-NMR (75 MHz, CDCl3):
3 3
2
7
26
2
4
7
52.02; H, 4.09; N, 8.95.
δ 191.4, 173.4, 144.6, 142.9, 133.9, 125.4, 122.2,
2
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
119.2, 105.6, 80.6, 77.4, 73.4, 66.5, 53.1, 36.3, 33.2,
25.2, 16.2; MS: m/z (M + H) 600. Anal. Calcd for
+
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological
Potent Molecules
C H ClN O S: C, 55.95; H, 4.86; N, 9.32. Found: C,
tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-phenylthiazolidin-4-
one (9a–n). A mixture of 7 (0.01 mol) and substituted
2
8
29
4 7
54.19; H, 4.62; N, 9.15.
2
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
o-phenylenediamine (2 mmol) catalytic amount of HCl
was grounded thoroughly and transferred to a 50-mL
flask. After adding a few drops of DMF, the mixture was
irradiated in a microwave oven at 180 W for 4–7 min at
110°C. The progress of reaction was monitored by TLC,
with a mixture of ethanol and water (9:1) as the eluent.
On completion, the reaction mixture was cooled, ice-cold
distilled water was added, and stirred for a while wherein
a precipitate was observed. The precipitate was collected
by filtration, washed with water, dried, and recrystallized
from ethanol water. In classical method, reaction mixtures
were grounded thoroughly and transferred to a 50-mL
flask. The mixture was refluxed in DMF (20 mL) over a
hot plate stirrer. The progress of reaction was monitored
by TLC. After completion of the reaction, the product
was purified by column chromatography on silica gel
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
dioxol-5-yl)-4-oxo-3-p-tolylthiazolidin-5-yl)acetic acid (8e).
mp 197–199°C. HNMR (300 MHz, CDCl ): δ 11.45 (s,
H, CO H), 8.20 (d, J = 8.4 Hz, 2H, Ar–H), 8.04 (s, 1H,
Ar–H), 7.54 (d, J = 9.1 Hz, 2H, Ar–H), 7.36 (d,
J = 8.33 Hz, 2H, Ar–H), 7.12 (d, J = 8.3 Hz, 2H, Ar–H),
.14 (s, 1H, CHS), 5.65 (d, J = 4.2 Hz, 1H, C H), 4.60
t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C H), 4.54 (s, 2H,
OCH ), 3.92–3.86 (m, 1H, C H), 3.22 (dd, J = 9.1,
.2 Hz, 1H, C H), 2.34 (d, 2H, CH ), 2.21 (s, 3H, CH ),
.51 (s, 3H, CH ), 1.29 (m, 3H, CH ); C-NMR
75 MHz, CDCl ): δ 191.4, 173.4, 144.6, 142.9, 133.9,
25.4, 122.2, 119.2, 105.6, 80.6, 77.4, 73.4, 66.5, 53.1,
6.3, 33.2, 25.2, 16.2; MS: m/z (M + H) 600. Anal.
Calcd for C H ClN O S: C, 55.95; H, 4.86; N, 9.32.
Found: C, 54.19; H, 4.62; N, 9.15.
2
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
dioxol-5-yl)-3-(3-hydroxyphenyl)-4-oxothiazolidin-5-yl)acetic
acid (8f). mp 227–229°C. HNMR (300 MHz, CDCl ): δ
1.42 (s, 1H, CO H), 8.24 (d, J = 8.7 Hz, 2H, Ar–H), 8.03
s, 1H, Ar–H), 7.56 (d, J = 9.2 Hz, 2H, Ar–H), 7.14–6.70
m, 4H, Ar–H), 6.14 (s, 1H, CHS), 5.76 (d, J = 3.6 Hz,
H, C H), 5.42 (s, 1H, OH), 4.96 (d, J = 5.2 Hz, 1H,
CH), 4.51 (t, J = 3.9 Hz, 1H, C H), 4.54 (s, 2H, OCH ),
1
3
1
2
6
(
1
2
2
4
4
1
(
1
3
3 2 3
1
3
3
3
3
+
28
29
4 7
(60–120 mesh) with hexane–ethyl acetate as eluent.
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
5
-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
6
-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
phenylthiazolidin-4-one (9a).
1
1
3
mp 221–223°C. HNMR
1
(
(
2
(500 MHz, DMSO): δ 9.32 (s, 1H, –NH), 8.06 (s, 1H,
Ar–H), 7.52 (d, J = 9.2 Hz, 4H, Ar–H), 7.44 (d,
J = 8.9 Hz, 2H, Ar–H), 7.21 (d, J = 8.4 Hz, 2H, Ar–H),
6.73–7.35 (m, 5H, Ar–H), 6.15 (s, 1H, CHS), 5.73 (d,
J = 4.2 Hz, 1H, C H), 4.69 (t, J = 3.9 Hz, 1H, C H),
1
1
2
2
1
2
3
.93–3.96 (m, 1H, C H), 3.26 (dd, J = 9.1, 4.2 Hz, 1H,
4
4.65 (t, 1H, CH), 4.52 (s, 2H, OCH ), 3.92–3.89 (m, 1H,
2
C H), 2.34 (d, 2H, CH ), 1.53 (s, 3H, CH ), 1.38 (m, 3H,
3
2
3
C H), 3.31 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.38 (d, 2H,
4
3
13
13
CH3);
C-NMR (75 MHz, CDCl ): δ 175.6, 171.6,
3
CH ), 1.53 (s, 3H, CH ), 1.30 (m, 3H, CH ); C-NMR
2 3 3
1
1
6
58.3, 144.2, 143.2, 134.6, 134.4, 130.6, 128.6, 122.2,
20.1, 119.4, 114.6, 111.8, 107.6, 106.8, 81.8, 78.6, 74.8,
4.9, 54.9, 41.1, 38.9, 35.3; MS: m/z (M + H) 545.
Anal. Calcd for C H ClN O S: C, 53.78; H, 4.52; N,
.29. Found: C, 53.52; H, 4.35; N, 8.99.
2
triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]
dioxol-5-yl)-3-(4-hydroxyphenyl)-4-oxothiazolidin-5-yl)acetic
acid (8g). mp 256–258°C. HNMR (300 MHz, CDCl ): δ
1.39 (s, 1H, CO H), 8.22 (d, J = 8.7 Hz, 2H, Ar–H), 8.06
s, 1H, Ar–H), 7.52 (d, J = 9.2 Hz, 2H, Ar–H), 7.14–6.87
m, 4H, Ar–H), 6.14 (s, 1H, CHS), 5.76 (d, J = 3.6 Hz,
H, C H), 5.42 (s, 1H, OH), 4.96 (d, J = 5.2 Hz, 1H,
CH), 4.51 (t, J = 3.9 Hz, 1H, C H), 4.54 (s, 2H, OCH ),
.93–3.96 (m, 1H, C H), 3.26 (dd, J = 9.1, 4.2 Hz, 1H,
(75 MHz, DMSO): δ 151.4, 143.8, 141.2, 134.2, 128.2,
1
3
26.8, 122.1, 118.8, 104.2, 80.4, 77.9, 73.8, 66.1, 53.0,
7.2, 33.9, 25.9; MS: m/z (M + H) 545. Anal. Calcd for
+
+
2
7
27
4
8
C H ClN O S: C, 60.13; H, 4.74; N, 12.75. Found: C,
33 31 6 5
9
6
0.01; H, 4.54; N, 12.55.
-(2-((3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-
5
-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
(3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
(
1
1
3
phenylthiazolidin-4-one (9b).
mp 227–229°C. HNMR
1
(
(
2
(500 MHz, DMSO): δ 9.27 (s, 1H, –NH), 8.20 (s, 1H,
Ar–H), 8.04 (s, 1H, Ar–H), 7.51 (d, J = 9.2 Hz, 2H,
Ar–H), 7.44 (d, J = 8.9 Hz, 2H, Ar–H), 7.21 (d, 2H, Ar–
H), 6.73–7.35 (m, 5H, Ar–H), 6.15 (s, 1H, CHS), 5.73
(d, J = 4.2 Hz, 1H, C H), 4.69 (t, J = 3.9 Hz, 1H, C H),
1
1
2
2
1
2
3
4
4.65 (t, 1H, CH), 4.52 (s, 2H, OCH ), 3.92–3.89 (m, 1H,
2
C H), 2.34 (d, 2H, CH ), 1.53 (s, 3H, CH ), 1.38 (m, 3H,
3
2
3
C H), 3.31 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.38 (d, 2H,
4
3
13
13
CH3);
C-NMR (75 MHz, CDCl ): δ 173.6, 171.6,
3
CH ), 1.53 (s, 3H, CH ), 1.30 (m, 3H, CH ); C-NMR
2 3 3
1
1
6
54.1, 143.2, 142.1, 133.6, 131.4, 129.6, 128.1, 122.6,
20.5, 115.4, 112.6, 111.8, 107.6, 106.8, 81.8, 78.6, 76.8,
5.9, 56.9, 42.1, 36.9, 34.3; MS: m/z (M + H) 545.
Anal. Calcd for C H ClN O S: C, 53.78; H, 4.52; N,
(75 MHz, DMSO): δ 151.4, 143.8, 141.2, 134.2, 128.2,
1
3
26.8, 122.1, 118.8, 104.2, 80.4, 77.9, 73.8, 66.1, 53.0,
7.2, 33.9, 25.9; MS: m/z (M + H) 694. Anal. Calcd for
+
+
2
7
27
4
8
C H Cl N O S: C, 57.14; H, 4.36; N, 12.12. Found: C,
30 30 2 6 5
9
.29. Found: C, 53.42; H, 4.25; N, 9.19.
5
6.98; H, 4.14; N, 12.01.
5
-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
5-((1H-Benzo[d]imidazol-2-yl)methyl)-3-(4-chlorophenyl)-2-
2,2-dimethyl-6-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)
((3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Srinivas, M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
Vol 000
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)
Ar–H), 7.49 (d, J = 9.1 Hz, 2H, Ar–H), 7.41 (d,
J = 8.5 Hz, 2H, Ar–H), 7.34 (d, J = 9.3 Hz, 2H, Ar–H),
1
thiazolidin-4-one (9c).
mp 248–250°C.
HNMR
(500 MHz, DMSO): δ 9.17 (s, 1H, –NH), 8.05 (s, 1H,
6
.79 (d, J = 9.6 Hz, 2H, Ar–H), 6.14 (s, 1H, CHS), 5.69
Ar–H), 7.50 (d, J = 9.2 Hz, 4H, Ar–H), 7.42 (d,
J = 8.9 Hz, 2H, Ar–H), 7.20 (d, 2H, Ar–H), 7.10–6.95
(d, J = 4.2 Hz, 1H, C H), 4.65 (t, 1H, CH), 4.53 (t,
1
J = 3.9 Hz, 1H, C H), 4.52 (s, 2H, OCH ), 3.90–3.86 (m,
2
2
(m, 4H, Ar–H), 6.13 (s, 1H, CHS), 5.71 (d, J = 4.2 Hz,
1
H, C H), 3.19 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.30 (d,
4
3
13
1
H, C H), 4.66 (t, J = 3.9 Hz, 1H, C H), 4.60 (t, 1H,
2H, CH ), 1.49 (s, 3H, CH ), 1.25 (m, 3H, CH ); C-
2 3 3
1
2
CH), 4.50 (s, 2H, OCH ), 3.92–3.89 (m, 1H, C H), 3.31
2
4
NMR (75 MHz, DMSO): δ 190.2, 173.2, 143.6, 141.9,
(
(
dd, J = 9.1, 4.2 Hz, 1H, C H), 2.38 (d, 2H, CH ), 1.53
3 2
1
134.5, 128.2, 126.5, 122.2, 118.2, 104.3, 80.4, 77.2, 73.1,
3
+
s, 3H, CH ), 1.30 (m, 3H, CH ); C-NMR (75 MHz,
66.2, 52.1, 36.4, 33.1; MS: m/z (M + H) 739. Anal.
3
3
DMSO): δ 151.1, 143.8, 141.2, 138.9, 134.2, 128.2,
Calcd for C H Cl N O S: C, 53.60; H, 3.96; N, 13.27.
33
29
2 7 7
1
26.8, 122.1, 118.8, 104.2, 80.4, 77.9, 73.8, 66.1, 53.0,
Found: C, 53.49; H, 3.79; N, 12.95.
+
37.2, 33.9, 25.9; MS: m/z (M + H) 693. Anal. Calcd for
5
-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
C H Cl N O S: C, 57.13; H, 4.36; N, 12.12. Found: C,
6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
3
3
30
2 6 5
5
6.81; H, 4.14; N, 12.01.
5
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-o-
1
tolylthiazolidin-4-one (9g).
mp 247–249°C. HNMR
-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-3-(4-
chlorophenyl)-2-((3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-
,2,3-triazol-4-yl)methoxy)-2,2-dimethyltetrahydrofuro[2,3-d]
(300 MHz, DMSO): δ 9.19 (s, 1H, –NH), 8.06 (s, 1H,
1
Ar–H), 7.50 (d, J = 9.1 Hz, 2H, Ar–H), 7.42 (d, 2H,
Ar–H), 7.38 (d, J = 8.5 Hz, 2H, Ar–H), 7.34 (d, 2H,
Ar–H), 7.29–7.32 (m, 4H, Ar–H), 6.14 (s, 1H, CHS),
[
1,3]dioxol-5-yl)thiazolidin-4-one (9d).
HNMR (500 MHz, DMSO): δ 9.27 (s, 1H, –NH), 8.26
mp 232–234°C.
1
(
4
s, 1H, Ar–H), 8.04 (s, 1H, Ar–H), 7.51 (d, J = 9.2 Hz,
H, Ar–H), 7.44 (d, J = 8.9 Hz, 4H, Ar–H), 7.21 (d, 1H,
5.65 (d, J = 4.2 Hz, 1H, C H), 4.60 (t, 1H, CH), 4.53 (t,
1
J = 3.9 Hz, 1H, C H), 4.54 (s, 2H, OCH ), 3.92–3.86 (m,
2
2
Ar–H), 7.11 (d, 1H, Ar–H), 6.15 (s, 1H, CHS), 5.73 (d,
J = 4.2 Hz, 1H, C H), 4.69 (t, J = 3.9 Hz, 1H, C H),
1H, C H), 3.22 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.34 (d,
4
3
1
2
2H, CH ), 2.21 (s, 3H, CH ), 1.51 (s, 3H, CH ), 1.29 (m,
2
3
3
13
4
.65 (t, 1H, CH), 4.52 (s, 2H, OCH ), 3.92–3.89 (m, 1H,
2
3H, CH ); C-NMR (75 MHz, DMSO): δ 191.4, 173.4,
3
C H), 3.31 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.38 (d, 2H,
144.6, 142.9, 133.9, 125.4, 122.2, 119.2, 105.6, 80.6,
4
3
1
3
+
CH ), 1.53 (s, 3H, CH ), 1.30 (m, 3H, CH ); C-NMR
77.4, 73.4, 66.5, 53.1, 36.3, 33.2; MS: m/z (M + H)
2
3
3
(75 MHz, DMSO): δ 151.1, 143.5, 141.0, 134.1, 128.4,
6
74. Anal. Calcd for C H ClN O S: C, 60.66; H, 4.94;
34 33 6 5
1
26.2, 122.0, 116.8, 102.2, 80.1, 77.6, 73.2, 66.0, 53.0,
N, 12.48. Found: C, 60.26.; H, 4.62; N, 12.15.
+
37.6, 33.1; MS: m/z (M + Na) 749. Anal. Calcd for
5
-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
C H Cl N O S: C, 54.14; H, 4.01; N, 11.54. Found: C,
((3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
3
3
29
3 6 5
5
3.98; H, 3.94; N, 11.31.
5
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
1
o-tolylthiazolidin-4-one (9h).
mp 257–248°C. HNMR
-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(4-
(500 MHz, DMSO): δ 9.17 (s, 1H, –NH), 8.29 (s, 1H,
6
Ar–H), 8.06 (s, 1H, Ar–H), 7.50 (d, J = 9.1 Hz, 2H,
Ar–H), 7.42 (d, J = 8.1 Hz, 2H, Ar–H), 7.38 (d,
J = 8.5 Hz, 2H, Ar–H), 7.34 (d, 2H, Ar–H), 7.29 (d,
J = 9.2 Hz, 1H, Ar–H), 7.14 (d, J = 8.6 Hz, 1H, Ar–H),
nitrophenyl)thiazolidin-4-one (9e).
mp 256–258°C.
1
HNMR (500 MHz, DMSO): δ 9.17 (s, 1H, –NH), 8.21 (d,
J = 8.4 Hz, 2H), 8.01 (s, 1H, Ar–H), 7.49 (d, J = 9.1 Hz,
2
4
CHS), 5.69 (d, J = 4.2 Hz, 1H, C H), 4.65 (t, 1H, CH),
4
H, Ar–H), 7.41 (d, J = 8.5 Hz, 2H, Ar–H), 7.30–7.34 (m,
H, Ar–H), 6.79 (d, J = 9.6 Hz, 2H, Ar–H), 6.14 (s, 1H,
6.14 (s, 1H, CHS), 5.65 (d, J = 4.2 Hz, 1H, C H), 4.60
1
(t, 1H, CH), 4.53 (t, J = 3.9 Hz, 1H, C H), 4.54 (s, 2H,
2
1
OCH
), 3.92–3.86 (m, 1H, C H), 3.22 (dd, J = 9.1,
2 4
.53 (t, J = 3.9 Hz, 1H, C H), 4.52 (s, 2H, OCH ),
4.2 Hz, 1H, C H), 2.34 (d, 2H, CH ), 2.21 (s, 3H, CH ),
2 2
3
2
3
13
3.90–3.86 (m, 1H, C H), 3.19 (dd, J = 9.1, 4.2 Hz, 1H,
1.51 (s, 3H, CH ), 1.29 (m, 3H, CH ); C-NMR
3 3
4
C H), 2.30 (d, 2H, CH ), 1.49 (s, 3H, CH ), 1.25 (m, 3H,
CH3); C-NMR (75 MHz, DMSO): δ 190.2, 173.2, 143.6,
3
2
3
(75 MHz, DMSO): δ 191.4, 173.4, 144.6, 142.9, 133.9,
13
125.4, 122.2, 119.2, 105.6, 80.6, 77.4, 73.4, 66.5, 53.1,
+
1
7
7
41.9, 134.5, 128.2, 126.5, 122.2, 118.2, 104.3, 80.4,
7.2, 73.1, 66.2, 52.1, 36.4, 33.1, 25.4; MS: m/z (M + H)
36.3, 33.2; MS: m/z (M + H) 708. Anal. Calcd for
+
C H Cl N O S: C, 57.71; H, 4.56; N, 11.88. Found: C,
34
32
2 6 5
04. Anal. Calcd for C H ClN O S: C, 56.70; H, 4.29;
57.26.; H, 4.22; N, 11.45.
3
3
30
7 7
N, 13.92. Found: C, 56.49; H, 4.09; N, 13.75.
5
-((1H-Benzo[d]imidazole-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
5
-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
(3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxolol-5-yl)-3-p- 1
(
tolylthiazolidine-4-one (9i).
mp 207–209°C. HNMR
(
4-nitrophenyl)thiazolidin-4-one (9f).
HNMR (500 MHz, DMSO): δ 9.14 (s, 1H, –NH), 8.36
s, 1H, Ar–H), 8.19 (d, J = 8.4 Hz, 2H), 8.01 (s, 1H,
mp 247–248°C.
(300 MHz, DMSO): δ 9.12 (s, 1H, –NH), 8.20 (d,
J = 8.4 Hz, 2H, Ar–H), 8.04 (s, 1H, Ar–H), 7.59 (d,
J = 9.4 Hz, 2H, Ar–H), 7.44 (d, J = 9.1 Hz, 2H, Ar–H),
1
(
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Microwave-assisted Synthesis of Hybrid Heterocyclics as Biological
Potent Molecules
7.32 (d, J = 8.9 Hz, 2H, Ar–H), 7.21 (d, J = 8.3 Hz, 2H,
J = 8.2 Hz, 1H, Ar–H), 7.14–7.10 (m, 4H, Ar–H), 6.12
Ar–H), 7.12 (d, J = 8.3 Hz, 2H, Ar–H), 6.14 (s, 1H,
(s, 1H, CHS), 5.74 (d, J = 3.6 Hz, 1H, C H), 5.40 (s, 1H,
1
CHS), 5.65 (d, J = 4.2 Hz, 1H, C H), 4.60 (t, 1H, CH),
OH), 4.96 (d, J = 5.2 Hz, 1H, CH), 4.49 (t, J = 3.9 Hz,
1H, C H), 4.50 (s, 2H, OCH ), 3.93–3.90 (m, 1H, C H),
1
4
.53 (t, J = 3.9 Hz, 1H, C H), 4.54 (s, 2H, OCH ),
2 2
2
2
4
3
.92–3.86 (m, 1H, C H), 3.22 (dd, J = 9.1, 4.2 Hz, 1H,
3.21 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.31 (d, 2H, CH ),
1.51 (s, 3H, CH ), 1.35 (m, 3H, CH ); C-NMR
3 3
4
3 2
13
C H), 2.34 (d, 2H, CH ), 2.21 (s, 3H, CH ), 1.51 (s, 3H,
CH ), 1.29 (m, 3H, CH ); C-NMR (75 MHz, DMSO):
3
2
3
1
3
(75 MHz, DMSO): δ 172.6, 156.1, 141.2, 140.2, 131.6,
130.4, 129.1, 124.6, 123.2, 121.1, 115.4, 113.1, 112.8,
104.6, 103.2, 82.8, 75.6, 72.8, 62.9, 53.9, 41.1, 37.9,
3
3
δ 192.4, 175.4, 142.6, 139.9, 136.7, 132.9, 124.4, 121.2,
17.2, 104.6, 82.6, 78.4, 73.1, 64.5, 52.1, 35.3, 31.2,
1
2
+
+
5.2, 21.4, 16.2; MS: m/z (M + H) 673. Anal. Calcd for
33.3, 26.1; MS: m/z (M + Na) 729. Anal. Calcd for
C H ClN O S: C, 60.66; H, 4.94; N, 5.27. Found: C,
C H Cl N O S: C, 55.86; H, 4.26; N, 5.25. Found: C,
3
4
33
6
5
33 30
2 6 6
60.49; H, 4.62; N, 5.15.
55.62; H, 4.15; N, 5.09.
5
-((6-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
(3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
5-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(4-
(
1
p-tolylthiazolidin-4-one (9j).
300 MHz, DMSO): δ 9.12 (s, 1H, –NH), 8.22 (d,
J = 8.4 Hz, 2H, Ar–H), 8.02 (s, 1H, Ar–H), 7.56 (d,
J = 9.4 Hz, 2H, Ar–H), 7.42 (d, J = 9.1 Hz, 2H, Ar–H),
mp 217–219°C. HNMR
hydroxyphenyl)thiazolidin-4-one (9m).
mp 266–268°C.
1
(
HNMR (300 MHz, DMSO): δ 8.20 (d, J = 8.7 Hz, 2H,
Ar–H), 8.02 (s, 1H, Ar–H), 7.49 (d, J = 9.2 Hz, 2H,
Ar–H), 7.14–7.09 (m, 4H, Ar–H), 6.16 (s, 1H, CHS),
7.31 (d, J = 8.9 Hz, 2H, Ar–H), 7.20 (d, J = 8.3 Hz, 1H,
5.73 (d, J = 3.6 Hz, 1H, C H), 5.41 (s, 1H, OH), 4.94 (d,
1
Ar–H), 7.12 (d, J = 8.3 Hz, 2H, Ar–H), 6.15 (s, 1H,
J = 5.2 Hz, 1H, CH), 4.51 (t, J = 3.9 Hz, 1H, C H), 4.54
2
CHS), 5.63 (d, J = 4.2 Hz, 1H, C H), 4.61 (t, 1H, CH),
(s, 2H, OCH ), 3.96–3.92 (m, 1H, C H), 3.24 (dd,
1
2
4
4
.53 (t, J = 3.9 Hz, 1H, C H), 4.51 (s, 2H, OCH ),
J = 9.1, 4.2 Hz, 1H, C H), 2.33 (d, 2H, CH ), 1.53 (s,
3H, CH ), 1.38 (m, 3H, CH ); C-NMR (75 MHz,
3 3
2
2
3 2
13
3.92–3.89 (m, 1H, C H), 3.23 (dd, J = 9.1, 4.2 Hz, 1H,
4
C H), 2.35 (d, 2H, CH ), 2.20 (s, 3H, CH ), 1.50 (s, 3H,
DMSO): δ 171.2, 153.1, 142.2, 141.1, 136.6, 134.4,
129.6, 128.4, 122.2, 120.1, 114.4, 112.2, 111.3, 105.6,
103.8, 80.8, 76.6, 74.8, 65.3, 57.0, 42.5, 36.4, 34.1; MS:
3
2
3
1
3
CH ), 1.25 (m, 3H, CH ); C-NMR (75 MHz, DMSO):
3
3
δ 192.4, 171.4, 142.6, 140.9, 131.9, 125.4, 123.8, 121.2,
18.2, 102.6, 81.6, 76.4, 72.4, 61.5, 52.1, 33.3, 25.2,
+
1
m/z (M + H) 675. Anal. Calcd for C H ClN O S: C,
33
31
6 6
+
23.2, 16.2; MS: m/z (M + H) 707. Anal. Calcd for
58.72; H, 4.62; N, 5.28. Found: C, 58.52; H, 4.39; N, 5.19.
C H Cl N O S: C, 57.71; H, 4.56; N, 4.88. Found: C,
5-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
3
4
32
2 6 5
5
7.59; H, 4.42; N, 4.75.
5
((3aR,5S,6S,6aR)-6-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
-((1H-Benzo[d]imidazol-2-yl)methyl)-2-((3aR,5S,6S,6aR)-
-((1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(3-
(
4-hydroxyphenyl)thiazolidin-4-one (9n).
mp 246–248°C.
6
1
HNMR (300 MHz, DMSO): δ 8.19 (d, J = 8.3 Hz, 2H,
hydroxyphenyl)thiazolidin-4-one (9k).
HNMR (300 MHz, DMSO): δ 9.09 (s, 1H, NH), 8.21
mp 237–239°C.
Ar–H), 8.02 (s, 1H, Ar–H), 7.38 (d, J = 9.2 Hz, 1H,
Ar–H), 7.11–7.09 (m, 4H, Ar–H), 6.12 (s, 1H, CHS),
1
(
d, J = 8.7 Hz, 2H, Ar–H), 8.03 (s, 1H, Ar–H), 7.52 (d,
J = 9.2 Hz, 2H, Ar–H), 7.14–7.10 (m, 4H, Ar–H), 6.12
s, 1H, CHS), 5.74 (d, J = 3.6 Hz, 1H, C H), 5.40 (s, 1H,
5.70 (d, J = 3.4 Hz, 1H, C H), 5.40 (s, 1H, OH), 4.83
1
(d, J = 5.1 Hz, 1H, CH), 4.50 (t, J = 3.5 Hz, 1H, C H),
2
(
4.52 (s, 2H, OCH ), 3.94–3.92 (m, 1H, C H), 3.22 (dd,
1
2
4
OH), 4.96 (d, J = 5.2 Hz, 1H, CH), 4.49 (t, J = 3.9 Hz,
J = 9.1, 4.2 Hz, 1H, C H), 2.30 (d, 2H, CH ), 1.51 (s,
3H, CH ), 1.34 (m, 3H, CH ); C-NMR (75 MHz,
3 3
3 2
13
1
3
1
H, C H), 4.50 (s, 2H, OCH ), 3.93–3.90 (m, 1H, C H),
2
2
4
.21 (dd, J = 9.1, 4.2 Hz, 1H, C H), 2.31 (d, 2H, CH ),
DMSO): δ 154.1, 141.2, 140.1, 134.6, 132.4, 128.6,
126.4, 121.2, 120.8, 113.4, 112.6, 110.3, 105.2, 103.2,
80.2, 76.2, 74.2, 65.1, 57.0, 42.1, 36.2, 34.1; MS: m/z
3
2
1
3
.51 (s, 3H, CH ), 1.35 (m, 3H, CH ); C-NMR
3
3
(75 MHz, DMSO): δ 173.6, 158.1, 142.2, 140.2, 133.6,
+
1
1
3
31.4, 130.1, 125.6, 121.2, 120.1, 116.4, 114.1, 111.8,
(M + H) 709. Anal. Calcd for C H Cl N O S: C,
33
30
2 6 6
05.6, 106.2, 80.8, 76.6, 73.8, 63.9, 52.9, 40.1, 36.9,
55.85; H, 4.24; N, 9.88. Found: C, 55.72; H, 4.19; N,
9.69.
+
2.3, 28.1; MS: m/z (M + H) 675. Anal. Calcd for
C H ClN O S: C, 58.71; H, 4.63; N, 5.25. Found: C,
3
3
31
6 6
5
8.62; H, 4.55; N, 5.19.
5
CONCLUSION
-((5-Chloro-1H-benzo[d]imidazol-2-yl)methyl)-2-
(3aR,5S,6S,6aR)-6-((1-(4-Chlorophenyl)-1H-1,2,3-triazol-4-yl)
methoxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-
(
In conclusion, a series of a new class of hybrid
heterocyclics 9a–n have been synthesized and evaluated
for their antibacterial activity; most of the compounds
showed appreciable antibacterial activity.
(
3-hydroxyphenyl)thiazolidin-4-one (9l).
HNMR (300 MHz, DMSO): δ 9.09 (s, 1H, NH), 8.21
mp 247–249°C.
1
(d, J = 8.7 Hz, 2H, Ar–H), 8.03 (s, 1H, Ar–H), 7.52 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Srinivas, M. Sunitha, K. Vasumathi Reddy, P. Karthik, and G. Rajesh Kumar
Vol 000
Acknowledgments. The authors are thankful to CSIR – New
Delhi for the financial support (project funding no. 02 (247)15/
EMR-II), Director of CSIR-IICT, Hyderabad, India, for NMR
and MS spectral analysis, and Principal of Vaagdevi Degree &
PG College Hanamkonda for his consistent encouragement.
[17] Rawal, R. K.; Prabhakar, Y. S.; Katti, S. B.; Declercq, E. Bio
Org Med Chem 2005, 13, 6771.
[
[
18] Kato, T.; Ozaki, T.; Tamura, K. J Med Chem 1999, 42, 3134.
19] Tanabe, Y.; Suzukamo, G.; Komuro, Y.; Imanishi, N.;
Morooka, S.; Enomoto, M.; Kojima, M.; Sanemistu, Y.; Mizutani, M.
Tetrahedron Lett 1991, 32, 379.
[
20] Kato, T.; Ozaki, T.; Ohi, N. Teraherdron Assymetry 1999, 10,
963.
21] Adachi, Y.; Suzuki, Y.; Homma, N.; Fukazawa, M.; Tamura,
K.; Nishie, I.; Kurumaro, O. Eur J Pharmacol 1999, 367, 267.
22] Ottana, R.; Mazzon, E.; Dugo, L.; Monforte, F.; Macari, F.;
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[
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet