A convenient one-pot synthesis of some new 3-(2-Phenyl-6-(2-thienyl)-4- pyridyl)hydroquinolin-2-ones under microwave irradiation and their antimicrobial activities

Article abstract of DOI:10.1080/10426500902915507

A series of 3-(2-phenyl-6-(2-thienyl)-4-pyridyl)hydroquinolin-2-ones 4a-o were synthesized in high yields by a one-pot cyclocondensation reaction under Kroehnke's reaction conditions using 2-chloro-3-formyl quinoline 1a-c, 2-acetyl thiophene 2, and various N-phenacylpyridinium bromides 3a-e in a mixture of ammonium acetate and acetic acid by microwave irradiation. All the compounds have been characterized by elemental analysis, FT-IR, 1H NMR, and 13C NMR spectral analysis. These compounds have been screened for their antimicrobial activities. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426500902915507

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A Convenient One-Pot Synthesis of
Some New 3-(2-Phenyl-6-(2-thienyl)-4-
pyridyl)hydroquinolin-2-ones Under
Microwave Irradiation and Their
Antimicrobial Activities
Niraj K. Ladani a , Manish P. Patel a & Ranjan G. Patel a
a Department of Chemistry , S.P. University , Vallabh Vidyanagar,
Gujarat, India
Published online: 24 Feb 2010.
To cite this article: Niraj K. Ladani , Manish P. Patel & Ranjan G. Patel (2010) A Convenient One-Pot
Synthesis of Some New 3-(2-Phenyl-6-(2-thienyl)-4-pyridyl)hydroquinolin-2-ones Under Microwave
Irradiation and Their Antimicrobial Activities, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:3, 658-662, DOI: 10.1080/10426500902915507
To link to this article: http://dx.doi.org/10.1080/10426500902915507
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Phosphorus, Sulfur, and Silicon, 185:658–662, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902915507
A CONVENIENT ONE-POT SYNTHESIS OF SOME NEW
3-(2-PHENYL-6-(2-THIENYL)-4-PYRIDYL)
HYDROQUINOLIN-2-ONES UNDER MICROWAVE
IRRADIATION AND THEIR ANTIMICROBIAL ACTIVITIES
Niraj K. Ladani, Manish P. Patel, and Ranjan G. Patel
Department of Chemistry, S.P. University, Vallabh Vidyanagar, Gujarat, India
A series of 3-(2-phenyl-6-(2-thienyl)-4-pyridyl)hydroquinolin-2-ones 4a–o were synthesized
in high yields by a one–pot cyclocondensation reaction under Kro¨hnke’s reaction con-
ditions using 2-chloro-3-formyl quinoline 1a–c, 2-acetyl thiophene 2, and various N-
phenacylpyridinium bromides 3a–e in a mixture of ammonium acetate and acetic acid
by microwave irradiation. All the compounds have been characterized by elemental analysis,
FT-IR, 1H NMR, and 13C NMR spectral analysis. These compounds have been screened for
their antimicrobial activities.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords 2-Acetyl thiophene; anti-microbial activity; 2-chloro-3-formyl quinoline; Kro¨hnke
reaction condition; microwave irradiation; various N-phenacylpyridinium bromides
INTRODUCTION
The polysubstituted pyridines are prominent building blocks in supramolecular chem-
istry with their π-stacking and directional H-bonding ability.1,2 The pyridyl heterocyclic
core is also a widespread subunit in numerous natural products and pharmaceuticals.3,4
These facts provide the basis for the development of new efficient synthetic pathways
for pyridines. Polysubstituted pyridines have been synthesized using an enormous num-
ber of preparative approaches such as [5+1]-type Hantzsch synthesis from 1,5-diketone
and nitrogen derivatives,5,6 [3+3]-type cyclization of chalcones and iminophosphoranes,7
[4+2] reactions of unsaturated imines with enolates,8 and [3+2+1]-type cyclization of α,β-
unsaturated compounds with α-substituted ketones and a nitrogen source.9 Among these
approaches, the latter approach is the most frequently employed. The two-step Kro¨hnke
synthesis10–12 via condensation of α,β-unsaturated ketones with pyridinium salts in the
presence of a mixture of ammonium acetate and acetic acid gives a variety of polysub-
stituted pyridines and has distinct advantages over the other routes. The drawback of this
Received 28 November 2008; accepted 23 March 2009.
The authors are thankful to the Department of Chemistry, S.P. University, for providing research facilities
and Vaibhav laboratory, Ahmedabad, for providing IR facilities.
Address correspondence to Ranjan G. Patel, Department of Chemistry, S.P. University, Vallabh Vidyanagar-
388 120, Gujarat, India. E-mail: patelranjanben@yahoo.com
658

NEW POLYSUBSTITUTED PYRIDINES
659
method is that pyridinium salts and α,β-unsaturated ketones have to be prepared first.
To overcome this problem Chao-Guo Yan and his coworkers13 have described a simple
but effective modification of the Kro¨hnke’s synthesis of pyridines in one-pot reactions of
N-phenacylpridinium bromide with aromatic aldehydes and acetophenone in the presence
of ammonium acetate and acetic acid under microwave irradiation to give polysubstituted
pyridine derivatives. A literature survey reveals that a number of pyridine14,15 derivatives
have been synthesized by Kro¨hnke reaction conditions using various aldehydes, but not a
single reference has been found where 2-chloro-3-formyl quinoline is used. We report in this
article biologically active new pyridine derivatives containing quinoline moiety by Kro¨hnke
reaction conditions utilizing this heterocyclic aldehyde16–18 by microwave irradiation.
Recently, the synthesis of organic compounds assisted by microwaves19,20 has become
an improved technique due to greater selectivity, rapid transfer of energy, significant prac-
tical simplicity, and pure products. Compared with classical heating, microwave-assisted
organic synthesis is characterized by spectacular acceleration, higher yields, milder reaction
conditions, and shorter reaction times as well as allowing synthesis to become environmen-
tally benign, improving many processes.21,22 The coupling of microwave technology with
one-pot multicomponent condensation reactions has received significant attention,23 since
two or more steps in the synthetic sequence can be carried out without the isolation of inter-
mediates. This leads to reduction of time and energy and constitutes overall an economical
way of developing new pharmaceutically important compounds.24
RESULTS AND DISCUSSION
Under microwave irradiation, 2-chloro-3-formyl quinoline 1a–c, 2-acetyl thiophene
2, and N-phenacylpyridinium bromide 3a–e in the presence of ammonium acetate and acetic
acid reacted smoothly to give 4a–o in high yield (78–90%). The required 2-chloro-3-formyl
quinoline 1a–c was prepared by Vilsmeier–Haack reaction,25 and N-phenacylpyridinium
bromide 3a–e was prepared by the procedure in the literature.26
The formation of compounds 4a–o involves the Kro¨hnke mechanism (see Scheme
S1, available online in the Supplemental Materials). The reaction is homogeneous and
proceeds via 2-chloro-3-formyl quinoline 1a–c, reacted first with 2-acetyl thiophene 2
to form an α,β-unsaturated ketone (4I). 4I is further reacted with N-phenacylpyridinium
bromide 3a–e to give 1,5-diketone derivatives (4II). The cyclization of 4II occurs with
ammonia, and finally the pyridine cation is eliminated with the formation of 3-(2-phenyl-
6-(2-thienyl)-4-pyridyl) hydroquinolin-2-ones27,28 4a–o. During the course of the reaction,
2-chloro quinoline is converted into 2-quinolones,29 The structures of compounds 4a–o were
confirmed by IR, 1H NMR, and 13C NMR spectra. The IR spectra of 4a exhibited absorptions
at 3180 for –NH–, 3010 for aromatic C H stretching, 1655 for (carbonyl group), and
1420–1600 cm−1 for C C aromatic and C N stretching of pyridine. The 1H NMR of 4a
showed a singlet at δ 12.12 for –NH– proton and aromatic protons resonate as multiplets
at 7.21–8.54. The 13C NMR spectrum of 4a showed signals at δ 128.89 ( CH C S ),
131.65 ( CO C ), 138.84 ( NH C ), 140.15 ( N C C ), 145.32 ( N C C-
S ), 146.40 ( CO C C ), 152.10 ( C N ), 156.03 ( C N ), 115.43–139.42 for
aromatic carbon, and the carbonyl carbon was observed at 161.10. The structure was further
confirmed by its mass spectral studies. It gave a molecular ion peak at m/z 381 (M+1)
corresponding to the molecular formula C24H16N2OS (Scheme 1). All the compounds were
screened for their antibacterial and antifungal activities using ciprofloxacin, ampicillin, and
griseofulvin as standard drugs.

660
N. K. LADANI ET AL.
O
CHO
Cl
R
N
+
+
+
_
COCH3
S
Br
N
R1
3a-e
1a-c
2
Acetic acid
MWI
NH4OAc
R
NH
O
Where,
R = H, CH3, OCH3
R1 = H, CH3, OCH3, Cl, F
N
S
R1
4a-o
Scheme 1
EVALUATION OF ANTIMICROBIAL ACTIVITY
The in vitro antimicrobial activity of compounds 4a–o was carried out against 24-h
old cultures of three bacteria: Escherichia coli as Gram-negative bacteria and Bacillus
substilis and Staphylococcus aureus as Gram-positive bacteria, and two fungi: Aspergillus
niger and Rhizopus oryzae by the disc-diffusion method.30,31 (For full details regarding
antimicrobial activity, see the Supplemental Materials online and Table S1.)
EXPERIMENTAL
All melting points were taken in open capillaries and are uncorrected. The monitoring
of the progress of all reactions and homogeneity of the synthesized compounds was carried
out by TLC. TLC was run using TLC aluminum sheets silica gel 60 F254 (Merck). Elemental
analysis (% C, H, N) was carried out by a Perkin Elmer 2400 CHN elemental analyzer.
IR spectra were recorded on a Shimadzu FTIR 8401 spectrophotometer using KBr pellets.
1H NMR and 13C NMR spectra were recorded on a Bruker Avance 400 MHz spectrometer
using solvent peak as the internal standard. Mass spectra were scanned on a Shimadzu
LCMS 2010 spectrometer. The microwave oven (700 W) used was a modified microwave
oven (RAGA’s Electromagnetic Systems).
Preparation of 3-(2-Phenyl-6-(2-thienyl)-4-pyridyl)hydroquinolin-2-ones
4a–o
2-Chloro-3-formyl quinoline (0.5 g, 0.0026 mol), 2-acetyl thiophene (0.28 mL,
0.0026 mol), N-phenacylpyridinium bromide (0.72 g, 0.0026 mol), ammonium acetate
(2.0 g, 0.026 mol), and acetic acid (5 mL) were charged in a 25 mL round bottom flask.

NEW POLYSUBSTITUTED PYRIDINES
661
Table I Substitutes on compounds 4a–o
Compound
R
R1
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
CH3
CH3
CH3
OCH3
OCH3
OCH3
Cl
CH3
OCH3
H
CH3
OCH3
H
CH3
OCH3
H
4j
4k
4l
4m
4n
4o
CH3
OCH3
H
CH3
OCH3
Cl
Cl
F
F
F
The flask was heated for 4–6 min at 118◦C under microwave irradiation (at 420 W). The
reaction was monitored by TLC; after the completion of reaction, the reaction mixture was
cooled to room temperature and stirred for 30 min, and the resulting solid was collected
by filtration and washed with water. The crude product was purified by leaching in an
equimolar mixture of chloroform and methanol (20 mL) to obtain the pure solid sample
4a–o. A sample characterization is given, and the remainder of the data are found in the
Supplemental Materials online.
3-(2-Phenyl-6-(2-thienyl)-4-pyridyl)hydroquinolin-2-one 4a
A pale yellow solid, mp 295–296◦C, yield: (90%). Anal. Calcd. for C24H16N2OS
(380.47): C, 75.76; H, 4.23; N, 7.36. Found: C, 75.61; H, 4.36; N, 7.54%. IR (KBr):
3180 (N H stretching), 3010 (aromatic C H stretching), 1655 (>C O stretching),
1420–1600 (C C aromatic and C N stretching of pyridine), 690 (C S stretching)
1
cm−1; H NMR (DMSO-d6): δ 7.21–8.54 (15H, m, Ar H), 12.12 (1H, s, NH) ppm; 13C
NMR: δ 115.43, 117.20, 118.62, 119.71, 122.65, 125.91, 127.13, 128.96, 129.07, 129.21,
129.27, 129.75, 139.42 ( C Ar ), 128.89 ( CH C S ), 131.65 ( CO C ), 138.84
( NH C ), 140.15 ( N C C ), 145.32 ( N C C S ), 146.40 ( CO C C ),
152.10 ( C N ), 156.03 ( C N ), 161.10 ( CO NH ) ppm; Mass: m/z: 381 (M+1).
CONCLUSION
A simple and efficient, one-pot procedure has been followed for the generation of
polysubstituted pyridines with microwave assistance. The method allows the introduction
of various substituted alkyl and aryl groups into the 2-, 4-, and 6-positions of pyridine. It
can be concluded from Table I that among all the compounds, 4e and 4m showed good
antibacterial activity against the tested organisms E. coli and S. aureus, while compounds
4d and 4m showed good antibacterial activity against the tested organism B. subtilis. The
compounds 4h, 4l, and 4m against the tested organism R. oryzae and compounds 4d and 4n
against the tested organism A. niger showed good antifungal activity, while the remaining

662
N. K. LADANI ET AL.
compounds of the series were moderately active against the tested organisms E. coli, S.
aureus, B. subtilis, A. niger, and R. oryzae.
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