Microwave induced one-pot synthesis of some new thiopyrano[2,3-b]quinolin- 2-ones under solvent-free conditions

Article abstract of DOI:10.1080/10426500701613170

A series of some new thiopyrano[2,3-b]quinolin-2-one 2a-i have been synthesized by the one pot reaction between 2-mercaptoquinoline-3- carbaldehyde1a-i and phenoxyacetic acid using TEA catalyst under microwave irradiation in solvent free conditions. The procedure is simple, environmentally benign and occurs in good yields. All the newly synthesized compounds were characterized by elemental analyses, IR, 1H NMR and mass spectral data. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701613170

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Microwave Induced One-
Pot Synthesis of Some New
Thiopyrano[2,3-b]quinolin-2-
ones under Solvent-Free
Conditions
M. Raghavendra a , Halehatty S. Bhojya Naik a
Bailure S. Sherigara a
a Department of P G Studies and Research in
&
Industrial Chemistry, School of Chemical Sciences ,
Kuvempu University , Shankaraghatta, Karnataka,
India
Published online: 09 May 2008.
To cite this article: M. Raghavendra , Halehatty S. Bhojya Naik & Bailure S.
Sherigara (2008) Microwave Induced One-Pot Synthesis of Some New Thiopyrano[2,3-
b]quinolin-2-ones under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon and
the Related Elements, 183:5, 1229-1235, DOI: 10.1080/10426500701613170
To link to this article: http://dx.doi.org/10.1080/10426500701613170
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Phosphorus, Sulfur, and Silicon, 183:1229–1235, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701613170
Microwave Induced One-Pot Synthesis of Some New
Thiopyrano[2,3-b]quinolin-2-ones under Solvent-Free
Conditions
M. Raghavendra, Halehatty S. Bhojya Naik,
and Bailure S. Sherigara
Department of P G Studies and Research in Industrial Chemistry,
School of Chemical Sciences, Kuvempu University, Shankaraghatta,
Karnataka, India
A series of some new thiopyrano[2,3-b]quinolin-2-one 2a-i have been synthesized
by the one pot reaction between 2-mercaptoquinoline-3-carbaldehyde1a-i and phe-
noxyacetic acid using TEA catalyst under microwave irradiation in solvent free
conditions. The procedure is simple, environmentally benign and occurs in good
yields. All the newly synthesized compounds were characterized by elemental anal-
1
yses, IR, H NMR and mass spectral data.
Keywords 2-Mercaptoquinoline-3-carbaldehyde; phenoxyacetic acid; solvent free;
thiopyrano[2,3-b]quinolin-2-one
INTRODUCTION
Five- and six-membered heterocyclic compounds, containing one or
two heteroatoms, fused to quinoline ring in a linear fashion are
found in natural products, as well as in synthetic compounds
of biological interest.1,2 They are known to exhibit antiallergenic,
antifungal,hypocholesterolemic, hypolemic, antibacterial, and antivi-
ral properties.3–7 In addition, various fused system of quinolines were
studied for their intercalative DNA binding properties.
A literature survey reveals the antitumor activity is due to the in-
tercalation between the base pairs of DNA and interferences with the
normal functioning of enzyme topoisomerase II, which is involved in
the breaking and releasing of DNA strands.8 The antitumor drugs that
Received 5 June 2007; accepted 20 July 2007.
The authors are thankful to The Director, Sophosticated Instrumentation Facility
Center, IISc, Bangalore, for the spectral data.
Address correspondence to Halehatty S. Bhojya Naik, Department of P G Studies and
Research in Industrial Chemistry, School of Chemical Sciences, Kuvempu University,
Shankaraghatta 577-451, Karnataka, India. E-mail: hsb naik@rediffmail.com
1229

1230
M. Raghavendra et al.
intercalate DNA are of growing interest in the field of anticancer deriva-
tives. Generally, they are characterized by planar chromophore, which
is often constituted by three or four condensed rings, which can inter-
calate into base pairs. Results of these various binding studies have
been useful in designing new and promising anticancer agent for clin-
ical use.9 DNA binding studies of pyrimidothienoquinolines have been
recently reported in the literature.10
The beneficial effects of microwave irradiation are playing an in-
creasing role in process chemistry, especially in cases where classical
methods require forcing conditions or prolonged reaction times. When
processes involve sensitive reagents, or there is the possibility of com-
pound decomposition under prolonged reaction conditions. Solvent-free
reaction techniques were successfully coupled with microwave because
they avoid the use of low boiling point solvents, which may sometimes
lead to explosions. Additionally, it can also avoid the use of poisonous
and expensive solvents, and as such can be environmentally benign, and
make manipulations much easier. The use of microwave for the synthe-
sis of organic compounds under solvent-free conditions proved to be an
efficient safe and environmentally benign techniques that with shorter
reaction time, high yields, and easier manipulation.11−14
RESULTS AND DISCUSSION
As mentioned earlier, condensed quinolines have a wide range of bio-
logical activities, therefore, they are useful materials in drug research.
Hence, in continuation of our studies in the synthesis of condensed
quinoline derivatives,15–18 due to their significant biological activities,
it appeared expedient to synthesize a condensed quinoline that is pre-
sented here in the present study.
2-Mercaptoquinoline-3-carbaldehyde1a–i, were found to be excellent
starting materials for the synthesis of novel thiopyrano[2,3-b]quinolin-
2-one derivatives. The starting compounds were prepared according to
the literature method.19 Then cyclization of 1a–i with phenoxyacetic
acid under microwave irradiation, in the presence of basic conditions in
one pot furnished the title compounds 2a–i, in good to excellent yields
(Scheme 1). The structure of the compounds was confirmed based on
elemental analysis and spectral data (Experimental section).
The IR spectrum of compound 2a–i showed an absence of SH,
NH, and CHO stretching frequency in the region 3100–3400 and be-
tween 1650–1670 cm−1, which appeared in the substituted 3-formyl-2-
mercapto quinolines.19 In addition IR (KBr) spectra of (2a–i) exhibiting
absorption bands in the region 1630–1645 cm−1 due to (C O) group.
1
The H NMR (DMSO-d6) spectrum of the compound 2a–i displayed

New Thiopyrano[2,3-b]quinolin-2-ones
1231
SCHEME 1
a singlet in the region δ 9.0–9.2 (s, 1H, H4), another singlet in the
region 8.75–8.95 (s, 1H, H5) and the aromatic protons were resonated
between δ 7.20–8.60, indicates the attachment of the reactive partner
to the quinoline moiety. Finally, above stated compound confirmed by
mass spectral data (Experimental section)
CONCLUSION
In conclusion, a simple efficient and environmentally benign method
has been developed for the synthesis of thiopyrano[2,3-b]quinolin-2-one
under microwave irradiation in solvent-free conditions. This microwave
irradiation method is superior from the view of a yield and reaction time
compared to the conventional (thermal) method (experimental section).
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected.
The FT-IR spectra were recorded on NICOLETAVATAR 360-FTIR

1232
M. Raghavendra et al.
instrument by using KBr pellets. The 1H NMR were recorded on a
BRUCKER AMX-400 spectrometer operating at 400 MHz. Mass spec-
tra were recorded on AGILENT LC-MSD-TRAP-XCT mass spectrom-
eter Elemental analyses were done on Vario EL. CHNOS elemental
analyzer.
General MW Procedure for the Synthesis of Substituted
Thiopyrano[2,3-b]quinolin-2-one 2a–i
Mixture of substituted quinoline 1a (0.180 g, 0.001 mol), phenoxyacetic
acid (0.152 g, 0.001 mol), TEA (0.1515 g, 0.0015 mol) and acetic anhy-
dride (0.306 g, 0.003 mol) were taken in 50 ml beaker, mixed well. The
contents were irradiated under microwave oven for about 4 min at an
interval of 30 s at 160 W. The completion of reaction was monitored
by TLC, the product 2a was poured into ice-cold water. The obtained
yellow color solid was filtered washed with water then recrystallized
from acetonitrile, gave 80% yield. The same procedure was used for the
synthesis of (2b–i)
Conventional Method
A mixture of substituted quinoline 1a (0.180 g, 0.001 mol) and phe-
noxyacetic acid (0.152 g, 0.001 mol) TEA (0.1515 g, 0.0015 mol), acetic
anhydride (0.306 g, 0.003 mol) and 20 ml of anhydrous DMF were taken
in 100 ml round-bottom flask, refluxed for 10 h. After completion of the
reaction confirmed by TLC, reaction mixture was concentrated, then
poured into ice-cold water. The obtained yellow color solid was filtered,
washed with water then recrystallized from acetonitrile, gave 59% yield.
The same procedure was used for the synthesis of (2b–i).
Physical and Spectral Data of the Products
3-Phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2a)
Solid, m.p. 194–196◦C; Yield 80% (MW), 59% (Conventional); Irradi-
ation time 4 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 9.10 (s, 1H, H4), 8.80 (s, 1H, H5), 7.30–8.50 (m,
9H, Ar−H); IR (KBr) ν (cm−1): 1630 (C = O); MS, m/z 305 [M+], Anal.
Calcd.. for C18H11NO2S: C, 70.81; H, 3.60; N, 4.59. Found: C, 70.79; H,
3.62; N, 4.57.
7-Methyl-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2b)
Solid, m.p. 213–215◦C; Yield 84% (MW), 63% (Conventional); Irradi-
ation time 5 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 2.35 (s CH3 protons), 9.2 (s, 1H, H4), 8.90 (s, 1H,

New Thiopyrano[2,3-b]quinolin-2-ones
1233
H5), 7.30–8.55 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1635 (C O); MS,
m/z 319 [M+], Anal. Calcd. for C19H13NO2S: C, 71.47; H, 4.07; N, 4.38.
Found: C, 71.49; H, 4.09; N, 4.35.
7-Methoxy-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-
2-one (2c)
Solid, m.p. 224–226◦C; Yield 81% (MW), 60% (Conventional); Irradi-
ation time 4 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 3.90 (s OCH3 protons), 9.10 (s, 1H, H4), 8.85 (s, 1H,
H5), 7.25–8.45 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1640 (C O); MS,
m/z 335 [M+], Anal. Calcd. for C19H13NO3S: C, 68.05; H, 3.88; N, 4.18.
Found: C, 68.02; H, 3.40; N, 4.21.
7-Bromo-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2d)
Solid, m.p. 245–247◦C; Yield 82% (MW), 55% (Conventional); Irradi-
ation time 4 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 9.0 (s, 1H, H4), 8.80 (s, 1H, H5), 7.35–8.60 (m, 8H,
Ar−H); IR (KBr) ν (cm−1): 1635 (C = O); MS, m/z 384 [M+], Anal. Calcd.
for C18H10BrNO2S: C, 56.25; H, 2.60; N, 3.64. Found: C, 56.23; H, 2.58;
N, 3.62.
8-Methyl-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2e)
Solid, m.p. 197–199◦C; Yield 79% (MW), 62% (Conventional); Irradi-
ation time 5 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 2.35 (s CH3 protons), 9.20 (s, 1H, H4), 8.90 (s, 1H,
H5), 7.25–8.50 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1645 (C O); MS,
m/z 319 [M+], Anal. Calcd. for C19H13NO2S: C, 71.47; H, 4.07; N, 4.38.
Found: C, 71.49; H, 4.04; N, 4.41.
8-Methoxy-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2f)
Solid, m.p. 203–205◦C; Yield 85% (MW), 57% (Conventional); Irradi-
ation time 5 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 3.95 (s OCH3 protons) 9.15 (s, 1H, H4), 8.80 (s, 1H,
H5), 7.30–8.55 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1630 (C O); MS,
m/z 335 [M+], Anal. Calcd. for C19H13NO3S: C, 68.05; H, 3.88; N, 4.18.
Found: C, 68.09; H, 3.85; N, 9.15.
7-Chloro-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2g)
Solid, m.p. 237–239◦C; Yield 84% (MW), 55% (Conventional); Irradi-
ation time 5 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 9.10(s, 1H, H4,), 8.75 (s, 1H, H5), 7.20–8.45 (m, 8H,
Ar−H); IR (KBr) ν (cm−1): 1635 (C O); MS, m/z 339 [M+], Anal. Calcd.

1234
M. Raghavendra et al.
for C18H10ClNO2S: C, 63.71; H, 2.94; N, 4.13. Found: C, 63.73; H, 2.97;
N, 4.16.
9-Methyl-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2h)
Solid, m.p. 217–219◦C; Yield 83% (MW), 64% (Conventional); Irradi-
ation time 4 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 2.30 (s CH3 protons), 9.20 (s, 1H, H4), 8.90 (s, 1H,
H5), 7.35–8.60 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1630 (C O); MS,
m/z 319 [M+], Anal. Calcd. for C19H13NO2S: C, 71.47; H, 4.07; N, 4.38.
Found: C, 71.49; H, 4.05; N, 4.35.
9-Methoxy-3-phenoxy-2H-thiopyrano[2,3-b]quinolin-2-one (2i)
Solid, m.p. 209–211◦C; Yield 80% (MW), 61% (Conventional); Irradi-
ation time 5 min (MW), reflux 10 h (conventional); 1H NMR (400 MHz,
DMSO-d6) δ (ppm): 3.90 (s OCH3 protons), 9.15 (s, 1H, H4), 8.95 (s, 1H,
H5), 7.30–8.55 (m, 11H, Ar−H); IR (KBr) ν (cm−1): 1635 (C O); MS,
m/z 335 [M+], Anal. Calcd. for C19H13NO3S: C, 68.05; H, 3.88; N, 4.18.
Found: C, 68.09; H, 3.92; N, 4.20.
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