Microwave-assisted one-pot synthesis of some new furo[2,3-b]quinolines using potassium carbonate under solvent-free conditions

Article abstract of DOI:10.1139/V07-124

A rapid, solvent-free microwave-assisted method has been developed for the synthesis of novel furoquinolines. The title compounds were achieved by the reaction between corresponding 2-hydroxy-3-formyl-quinolines (1a-1c) with chloroacetamide, ethylchloroac

Full text of DOI:10.1139/V07-124

1041
Microwave-assisted one-pot synthesis of some
new furo[2,3-b]quinolines using potassium
carbonate under solvent-free conditions
M. Raghavendra, Halehatty S. Bhojya Naik, and Bailure S. Sherigara
Abstract: A rapid, solvent-free microwave-assisted method has been developed for the synthesis of novel furo-
quinolines. The title compounds were achieved by the reaction between corresponding 2-hydroxy-3-formyl-quinolines
(1a–1c) with chloroacetamide, ethylchloroacetate, and phenacylbromide in specially designed microwave (MW) oven
for organic synthesis in unsealed borosil vessel in presence of potassium carbonate. In this method, isolation is accom-
plished by just treating the reaction mixture with water, and products were obtained in high yield. Hence, this method
was found to be very effective and ecofriendly. The structure of the newly synthesized compounds has been evaluated
1
on the basis of analytical, IR, H NMR, and mass spectral data.
Key words: furoquinoline, microwave irradiation, potassium carbonate, solvent-free conditions.
Résumé : On a mis au point une méthode rapide, sans solvant et assistée par les microondes pour la synthèse de
nouvelles furoquinoléines. Les synthèses des composés mentionnés dans le titre ont été réalisées en faisant réagir les
2-hydroxy-3-formylquinoléines correspondantes (1a–1c) avec du chloroacétamide, du chloroacétate d’éthyle et du bro-
mure de phénacylel, en présence de carbonate de potassium, dans un four à microondes spécialement conçu pour les
synthèses organiques dans un contenant en borosil non scellé. Dans cette méthode, on isole les produits par un simple
traitement du mélange réactionnel avec de l’eau et les rendements en produits obtenus sont élevés. On a donc trouvé
que cette méthode est très efficace et écologiquement acceptable. Les structures des nouveaux composés synthétisés ont
1
été déterminées sur la base d’analyses et de données de spectrométrie IR, RMN du H et de masse.
Mots-clés : furoquinoléine, irradiation par microondes, carbonate de potassium, conditions sans solvant.
[Traduit par la Rédaction] Raghavendra et al. 1044
Introduction
conventional heating methods (2–3). In addition, the limita-
tions of the microwave-assisted reactions in solvents,
namely, the development of high pressure and the need for
specialized sealed vessels, are circumvented via the solid-
catalyst strategy, which enables organic reactions to occur
rapidly at atmospheric pressures and scale up the reactions
on a preparative scale (4).
Furo[2,3-b]quinoline derivatives constitute an important
group of bioactive natural products, such as dictamnine,
acrophylline, confusameline, skimmianine, kokusaginine,
and aplopine (5–10). They were found to possess a wide-
range of biological properties, such as anti-allergic (5), anti-
inflammatory (6), cytotoxic (7), antiplatelet aggregation
(8–9), and the voltage-gated potassium channel blocking ac-
tivities (10). Due to their biological importance, several methods
have been reported for the synthesis of furoquinoline deriva-
tives (11–15). However, those methods involve multisteps,
are time-consuming, produce low yield, and more impor-
tantly, the use of more solvents makes those methods less
economic. So, there is still need for developing simple, effi-
cient and eco-friendly methods.
Synthetic organic reactions performed under non-
traditional conditions are gaining popularity, primarily to
circumvent growing environmental concerns (1). Micro-
wave-assisted heating is an invaluable synthesis technology,
since it often dramatically reduces reaction times, typically
from days or hours, minutes, or even seconds. It can also
provide pure products in quantitative yields. Solvent-free re-
action techniques are successfully coupled with microwave
(MW) to avoid the use of low boiling point solvents, which
may sometimes lead to explosions. Additionally, the use of
poisonous and expensive solvents can also be avoided to
make manipulations of the reactions much easier. The use of
microwave for the synthesis of organic compounds under
solvent-free conditions proved to be an efficient and safe
technique, as it requires shorter reaction times, gives higher
yield, and the reactions are easily carried out compared with
Received 5 April 2007. Accepted 4 September 2007.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 9 November 2007.
Hence, in continuation of our studies on microwave-
assisted organic synthesis of linearly condensed quinolines
(16–19), by adopting green chemistry, we wish to report
microwave-assisted novel synthesis of furo[2,3-b]quinoline
derivatives using solid base catalyst under solvent-free
microwave-irradiation conditions.
M. Raghavendra, H.S.B. Naik,1 and B.S. Sherigara.
Department of P G Studies and Research in Industrial
Chemistry, School of Chemical Sciences, Kuvempu
University, Shankaraghatta, Karnataka, India.
1Corresponding author (e-mail: hsb_naik@rediffmail.com).
Can. J. Chem. 85: 1041–1044 (2007)
doi:10.1139/V07-124
© 2007 NRC Canada

1042
Can. J. Chem. Vol. 85, 2007
Scheme 1.
R1
O
ClCH2CONH2
K2CO3, MW
O
NH2
N
(2a–2c)
O
R1
ClCH2COOC2H5
K2CO3, MW
R1
H
COOC2H5
O
N
N
OH
(3a–3c)
(1a–1c)
R1
H
R1
O
1a
BrCH2COC6H5
K2CO3, MW
1b CH3
O
N
1c OCH3
(4a–4c)
Thermal effects (dielectric heating) can result from
Results and discussion
dipolar polarization as a consequence of dipole–dipole inter-
actions between polar molecules and the electromagnetic
field. They originate in the dissipation of energy into heat as
an outcome of agitation and intermolecular friction of mole-
cules when dipoles change their mutual orientation at each
alternation of the electric field at a very high frequency.
This energy dissipation in the core of materials allows a
much more regular repartition in temperature when com-
pared with classical heating. Classical thermal phenomena
(conduction, convention, radiation, and so forth) only play a
secondary role in the a posteriori equilibration of tempera-
ture, and as a result of this, the rate of the reaction increases
in MW method.
The IR absorption bands observed in the region 3000–
3200 cm–1, due to tautomeric form of –NH and –OH stretch-
ing frequency, and in 1H NMR spectrum, a broad singlet due
to –NH at δ 11.0 and a singlet at δ 10.5 due to –CHO group
found in the starting compound (1a–1c) were absent in the
final compounds.
2-Hydoxy-3-formyl quinolines (1a–1c), were found to be
the excellent starting materials for the synthesis of novel
furoquinoline derivatives. The starting compounds were pre-
pared according to the literature method (20). In the present
study, the cyclization of (1a–1c) with phenacylbromide,
chloroacetamide, and ethylchloroacetate under microwave ir-
radiation in one pot furnished the title compounds (2a–2c),
(3a–3c), and (4a–4c) in good yields (Scheme 1).
The reaction proceeds through the nucleophilic substitu-
tion of a halogen. Then, the carbanion intermediate results
after treatment by a base, which adds on the aldehydic car-
bon atom with simultaneous elimination of water, resulting
in the formation of the cyclized products (21) (Scheme 1).
The temperature was measured by introducing the thermom-
eter inside the reaction mixture just at the end of the reac-
tion, and the temperature was found to be 130–135 °C. To
see whether these conditions work under non-microwave ex-
periment, reactions were carried out in a pre-heated oil bath.
It has been found that although the reaction did take place,
the yield was quite low. The acceleration of reactions by mi-
crowave exposure results from material–wave interactions
leading to thermal effects (which may be easily estimated by
temperature measurements) and specific (non-purely ther-
mal) effects. Clearly, a combination of these two contribu-
tions can be responsible for the observed effects.
The IR spectra of 3a exhibited the typical ester carbonyl
1
group absorption at 1680 cm–1. The H NMR (DMSO-d6)
spectrum of the compound (3a) displayed a triplet at δ 1.39
(3H), a quartet at 4.38 (CH2) characteristic of an ethyl
group, singlet at 8.56 (C3–H), and singlet at δ 8.22 (C4–H).
The aromatic proton signals appeared between 7.35–
8.10 ppm, indicating that the reactive partner was attached to
© 2007 NRC Canada

Raghavendra et al.
1043
the quinoline moiety. The structure of 3a was further con-
firmed by the appearance of the molecular-ion peak at m/z
241 (M+).
Ethyl furo[2,3-b]quinoline-2-carboxylate (3a)
Recrystallized from aq. DMF. Yield: 86% (MW). Mp:
1
251–253 °C. IR (KBr) cm–1: 1680. H NMR (400 MHz,
DMSO-d6): 1.39 (t, 3H, –CH3), 4.38 (q, 2H, –OCH2), 8.56
(s, C3–H), 8.22 (s, C4–H), 7.35–8.10 (m, 4H, Ar–H). MS
m/z: 241 (M+). Anal. calcd. for C14H11NO3: C, 69.70; H,
4.56; N, 5.80. Found: C, 69.74; H, 4.52; N, 5.84.
Material and methods
Melting points were determined in open capillaries and
are uncorrected. The FTIR spectra were recorded on
NICOLETAVATAR 360-FTIR instrument by using KBr pel-
Ethyl 6-methylfuro[2,3-b]quinoline-2-carboxylate (3b)
Recrystallized from aq. DMF. Yield: 88% (MW). Mp:
245–247 °C. IR (KBr) cm–1: 1675 cm–1. 1H NMR
(400 MHz, DMSO-d6): 2.16 (s, 3H, –CH3), 1.39 (t, 3H,
–CH3), 4.38 (q, 2H, –OCH2), 8.57 (s, C3–H), 8.24 (s, C4–H),
7.40–8.13 (m, 3H, Ar–H). MS m/z: 255 (M+). Anal. calcd.
for C15H13NO3: C, 70.58; H, 5.09; N, 5.49. Found: C, 70.53;
H, 5.06; N, 5.42
1
lets. The H NMR were recorded on a BRUKER AMX-400
spectrometer operating at 400 MHz and mass spectra on
AGILENT LC-MSD-TRAP-XCT mass spectrometer. Ele-
mental analyses were done on Vario EL CHNOS elemental
analyzer. Focused microwave irradiations were performed
with specially designed microwave oven (Biotage, Emrys
Optimizer operating at 300 W) for organic synthesis.
Ethyl 6-methoxyfuro[2,3-b]quinoline-2-carboxylate (3c)
Recrystallized from aq. DMF. Yield: 87% (MW). Mp:
Experimental
1
220–222 °C. IR (KBr) cm–1: 1670. H NMR (400 MHz,
DMSO-d6): 3.95 (3H, s, Ar–OCH3), 1.39 (t, 3H, –CH3), 4.38
(q, 2H, –OCH2), 8.58 (s, C3–H), 8.28 (s, C4–H), 7.37–8.12
(m, 3H, Ar–H). MS m/z: 255 (M+). Anal. calcd. for
C15H13NO3: C, 66.42; H, 4.79; N, 5.16. Found: C, 66.46; H,
4.83; N, 5.19.
General microwave procedure for the synthesis of
furo[2,3-b]quinolines
A mixture of 1a (1.730 g, 10 mmol), phenacylbromide
(1.990 g, 10 mmol), and anhyd. potassium carbonate
(1.380 g, 20 mmol) was ground for uniform mixing. The
mixture was then subjected to microwave irradiation in a mi-
crowave oven for 12 min at an interval of 1 min at 160 W to
complete the reaction (TLC). The reaction mixture was then
poured into water, stirred, and the solid obtained was filtered
and dried. The crude product was recrystallized from aq.
DMF to give 2.322 g (85%) of 4a. All other compounds
were prepared in a similar way with 85%–90% yield.
Furo[2,3-b]quinolin-2-yl(phenyl)methanone (4a)
Recrystallized from aq. DMF. Yield: 89% (MW). Mp:
1
236–237 °C. IR (KBr) cm–1: 1660. H NMR (400 MHz,
DMSO-d6): 8.60 (s, C3–H), 8.21 (s, C4–H), 7.49–8.18
(9H, m, Ar–H). MS m/z: 273 (M+). Anal. calcd. for
C18H11NO2: C, 79.12; H, 4.03; N, 5.12. Found: C, 79.16; H,
4.06; N, 5.00.
Physical and spectral data of the products
(6-Methylfuro[2,3-b]quinolin-2-yl)(phenyl)methanone (4b)
Recrystallized from aq. DMF. Yield: 90% (MW). Mp:
247–249 °C. IR (KBr) cm–1: 1670 cm–1. 1H NMR
(400 MHz, DMSO-d6): 2.26 (s, 3H, –CH3), 8.58 (s, C3–H),
8.24 (s, C4–H), 7.45–8.13 (8H, m, Ar–H). MS m/z: 287
(M+). Anal. calcd. for C19H13NO2: C, 79.44; H, 4.52; N,
4.87. Found: C, 79.47; H, 4.56; N, 4.83.
Furo[2,3-b]quinoline-2-carboxamide (2a)
Recrystallized from aq. DMF. Yield: 85% (MW). Mp:
226–228 °C. IR (KBr) cm–1: 3330, 3145 (CONH2). 1H NMR
(400 MHz, DMSO-d6): 7.50 (2H, bs, –CONH2), 8.55 (s,
C3–H), 8.20 (s, C4–H), 7.33–8.12 (m, 4H, Ar–H). MS m/z:
212 (M+). Anal. calcd. for C12H8N2O2: C, 67.92; H, 3.77; N,
13.20. Found: C, 67.90; H, 3.79; N, 13.22
(6-Methoxyfuro[2,3-b]quinolin-2-yl)(phenyl)methanone
(4c)
6-Methylfuro[2,3-b]quinoline-2-carboxamide (2b)
Recrystallized from aq. DMF. Yield: 86% (MW). Mp:
237–239 °C. IR (KBr) cm–1: 3340, 3155 (CONH2). 1H NMR
(400 MHz, DMSO-d6): 2.11 (s, 3H, –CH3), 7.53 (2H, bs,
–CONH2), 8.53 (s, C3–H), 8.24 (s, C4–H), 7.30–8.14 (m,
3H, Ar–H). MS m/z: 226 (M+). Anal. calcd. for C13H10N2O2:
C, 69.02; H, 4.42; N, 12.38. Found: C, 69.04; H, 4.47; N,
12.34.
Recrystallized from aq. DMF. Yield: 86% (MW). Mp:
1
260–262 °C. IR (KBr) cm–1: 1665. H NMR (400 MHz,
DMSO-d6) 4.10 (3H, s, Ar–OCH3), 8.56 (s, C3–H), 8.28 (s,
C4–H), 7.43–8.11 (8H, m, Ar–H). MS m/z: 303 (M+). Anal.
calcd. for C19H13NO3: C, 75.24; H, 4.29; N, 4.62. Found: C,
75.20; H, 4.24; N, 4.64.
6-Methoxyfuro[2,3-b]quinoline-2-carboxamide (2c)
Recrystallized from aq. DMF. Yield: 90% (MW). Mp:
250–252 °C. IR (KBr) cm–1: 3350, 3150 (CONH2). 1H NMR
(400 MHz, DMSO-d6): 3.90 (3H, s, Ar–OCH3), 7.54 (2H,
bs, –CONH2), 8.50 (s, C3–H), 8.18 (s, C4–H), 7.25–8.12 (m,
3H, Ar–H). MS m/z: 242 (M+). Anal. calcd. for C13H8N2O3:
C, 64.46; H, 4.13; N, 11.57. Found: C, 64.42; H, 4.16; N,
11.54.
Conclusion
In conclusion, a simple microwave-assisted method has
been developed for the synthesis of furo[2,3-b]quinolines
under solvent-free conditions in presence of K2CO3. This
microwave-irradiation method is superior from the view of
the yield, reaction time, and facial workup compared with
the conventional (thermal) method.
© 2007 NRC Canada

1044
Can. J. Chem. Vol. 85, 2007
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Acknowledgement
Authors are thankful to the Director, Sophosticated Instru-
mentation Facility Center, Indian Institute of Science (IISc),
Bangalore, for the spectral data.
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© 2007 NRC Canada