A facile one-pot microwave-induced synthesis of some novel selenolo[2,3-b]quinoline derivatives under solvent-free conditions

Article abstract of DOI:10.1080/10426500701690855

A rapid, solvent free microwave assisted synthetic strategy has been developed for the synthesis of some selenolo[2,3-b]quinoline derivatives using potassium carbonate by the reaction between 2-seleno-3-formyl-quinolines (2a-d) with 2-chloroacetamide and phenacylbromide. This method found to be very effective, products obtained in high yield, isolation is just treating the reaction mixture with water. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500701690855

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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A Facile One-Pot Microwave-
Induced Synthesis of Some
Novel Selenolo[2,3-b]quinoline
Derivatives 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: 04 Jun 2008.
To cite this article: M. Raghavendra , Halehatty S. Bhojya Naik & Bailure S. Sherigara
(2008) A Facile One-Pot Microwave-Induced Synthesis of Some Novel Selenolo[2,3-
b]quinoline Derivatives under Solvent-Free Conditions, Phosphorus, Sulfur, and Silicon
and the Related Elements, 183:6, 1501-1509
To link to this article: http://dx.doi.org/10.1080/10426500701690855
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Phosphorus, Sulfur, and Silicon, 183:1501–1509, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701690855
A Facile One-Pot Microwave-Induced Synthesis of Some
Novel Selenolo[2,3-b]quinoline Derivatives 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 rapid, solvent free microwave assisted synthetic strategy has been developed
for the synthesis of some selenolo[2,3-b]quinoline derivatives using potassium
carbonate by the reaction between 2-seleno-3-formyl-quinolines (2a–d) with 2-
chloroacetamide and phenacylbromide. This method found to be very effective, prod-
ucts obtained in high yield, isolation is just treating the reaction mixture with water.
Keywords Microwave irradiation; quinolines; selenolo[2,3-b]quinolines; solvent-free
conditions
INTRODUCTION
The use of microwave for the synthesis of organic compounds under
solvent-free conditions proved to be efficient safe and environmentally
benign techniques that with shorter reaction time, high yields, and
easier manipulation. Additionally, it can also avoid the use of poisonous
and expensive solvent, and as such can be environmentally benign, and
make manipulations much easier.1−2
Several polycyclic analogues of natural or synthetic antitumor agents
are well known, and have attracted considerable interest because of
their significant anticancer activity.3 There is a evidence that the an-
titumor activity is due to these compounds intercalation between the
Received 17 January 2007; accepted 8 August 2007.
M. Raghavendra is thankful to the Chairman, Kuvempu University, Shankaraghatta,
for providing research facilities and the Head of the Sophisticated Instruments Facility,
IISc, Bangalore, for 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, Karnataka, India. E mail: hsb naik@rediffmail.com
1501

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M. Raghavendra et al.
base pairs of DNA and interference with normal functioning of the en-
zyme topoisomerase II, which is involved in the breaking and releasing
of DNA strands.4 The intercalative binding of these drugs is due to the
presence of planar linearly fused tri and tetra cyclic systems.
Further, the biological and pharmaceutical activities of different se-
lenium compounds are gains special interest because it has been associ-
ated with modification of metal toxicity5 and with prevention of cancer.6
In addition to naturally occurring selenium compounds, certain syn-
thetic organoselenium compounds such as p-methoxybenzeneselenol,
benzylselenocyanate, 1,4-phenylenebisselenocyanate were found to in-
hibit azoxymethane-induced hepatocarcinogenesis in female F 344 rats
without clinical signs of toxicity,7−9 p-methoxybenzyl selenocyanate and
1, 4-phenylenebis (methylene) selenocyanate prevented both precancer-
ous cell growth and tumor growth in animals after being treated with a
colorectal cancer-inducing agent with no side effects.10 Moreover, some
patented phenylaminoalkyl selenides confirmed antihypertensive prop-
erties.
On the other hand, five- and six-membered heterocyclic compounds
containing one or two heteroatom fused to quinoline ring in a linear
fashion are found in natural products, as well as in synthetic compounds
of biological interest have antitumor and anticancer properties.11,12
They are also known to exhibit antiallergenic,13 antifungal,14 hypoc-
holesterolemic, hypolemic,15 antibacterial,16 and antiviral17 properties.
In addition, various condensed quinolines were studied for their inter-
calative DNA binding, cytotoxic, and antitumor activities.18
Due to their great biological properties, compounds containing the
quinoline system have been the subject of many synthetic studies. In
these directions, there has been increasing interest in the synthesis of
quinoline containing Se moieties to obtain improved chemoprevention
with lower toxic activity. So, in continuation of our studies on synthesis
of condensed quinolines19 by taking the advantage of microwave, we
wish to report on synthesis of novel selenolo[2,3-b]quinoline derivatives
under solvent free microwave irradiation conditions.
RESULTS AND DISCUSSION
The starting compounds 2-chloro-3-formylquinoline (1a–d), were pre-
pared according to literature method.20 The compounds 2-seleno-3-
formylquinoline (2a–d) were prepared by the action of sodium hydrose-
lenide on 2-chloro-3-formylquinolines (1a–d) (Scheme 1).
A wide range of substituted selenolo[2,3-b]quinolines such as (3a–d),
and (4a–d) were prepared by treating (2a–d) with phenacylbromide and
2-chloroacetamide under solvent free microwave irradiation conditions

Novel Selenolo[2,3-b]quinoline Derivatives
1503
SCHEME 1
in one pot to furnished the title compounds in good yields as shown
in (Scheme 2). The reaction was known21 to proceed through replacing
halogen of the reactants by selenium moiety, the carbanion results in
the intermediate by base, adds on the aldehydic carbon with simulta-
neous elimination of water resulting in the formation of products with
good yields. The structural elucidation of all the newly synthesized com-
pounds was established based on their IR, 1H NMR and mass spectral
data. (which are presented in the experimental section).
As an example, the IR spectrum of (3a) showed an absence of tau-
tomeric SeH, NH, groups and CHO stretching frequency in the region
of 3150–3300, and 1650 cm−1, which appeared in the 2-seleno-3-formyl-
quinoline (2a) were found to be absent in the IR spectrum of (3a). The
1H NMR spectrum of 2a exhibits singlet at δ 5.8 ppm corresponding
to tautomeric SeH, NH, group and singlet at δ 10.35 ppm correspond-
ing to −CHO group, the singlet in the intermediate near at δ 4.2 ppm
corresponding to an unreacted –SeCH2 group were found to be absent
in (3a) indicates the attachment of the reactive partner to quinoline
moiety. Further, compound (3a) showed signal at δ 8.50 for C4-H pro-
ton and signal at δ 8.62 for C3-H proton, this might be due to hydrogen

1504
M. Raghavendra et al.
SCHEME 2
bonding and anisotropy effect of the adjacent carbonyl groups. The other
aromatic protons resonated at δ 7.50–8.16 (4H). Finally, the structure
assigned was confirmed by its mass spectrum through the appearance
of a molecular ion peak at m/z 334 [M+]. The melting points, percentage
of yield and elemental data were shown in Table I.
MATERIALS AND METHODS
Melting points were determined in open capillaries and are uncor-
rected. The FT-IR spectra were recorded on NICOLETAVATAR 360-
FTIR instrument by using KBr pellets. The 1H NMR were recorded on a
BRUCKER AMX-400 spectrometer operating at 400 MHz. Mass spectra
were recorded on AGILENT LC-MSD-TRAP-XCT mass spectrometer

Novel Selenolo[2,3-b]quinoline Derivatives
1505
TABLE I Characterization Data of the Newly Synthesized
Compounds
Elemental analysis
Calcd./Found (%)
Microwave irradiation/Reflux
M.P. Yield
Compound
no.
Mol.
formula
(◦C)
(%)
Time/hr/min
C
H
N
2a
2b
2c
2d
3a
3b
3c
3d
4a
4b
4c
4d
255
91
1hour
C10H7NOSe
C11H9N0Se
50.84 2.96
50.80 3.00
52.81 3.63
52.81 3.63
49.64 3.41
49.64 3.43
52.81 3.63
52.81 3.63
64.28 3.27
64.30 3.24
65.14 3.71
65.18 3.68
62.29 3.55
62.32 3.52
65.14 3.71
65.20 3.73
52.36 2.90
52.39 2.94
53.97 3.46
53.94 3.42
51.14 3.27
51.16 3.30
53.97 3.46
53.94 3.42
5.93
5.99
5.60
3.63
5.26
5.28
5.60
5.60
4.16
4.12
4.00
4.06
3.82
3.86
4.00
3.96
10.18
10.20
9.68
9.64
9.18
9.22
9.68
9.64
247
266
240
235
208
231
208
237
217
229
225
90
92
90
89
88
85
88
89
90
88
90
1hour
1hour
C
11H9N02Se
11H9N0Se
C18H11NOSe
19H13NOSe
C19H13NO2Se
1hour
C
7
8
7
8
8
8
8
8
C
C
19H13NOSe
12H8N2OSe
C
C
13H10N2OSe
13H10N2O2Se
C13H10N2OSe
C
Elemental analyses were done on Vario EL. CHNOS elemental ana-
lyzer.
General Method for the Preparation of
2-Seleno-3-formylquinoline (2a)
Solution of sodium hydrogen selenide [freshly prepared from finely di-
vided selenium powder (1 g, 0.013 mol) and sodium borohydride (1 g,
0.026 mol) in water (50 ml)],22was added to 2-chloro-3-formylquinoline
(1a) (1.91 g, 0.01 mol) in ethanol (80 ml). The reaction mixture was re-
fluxed on water bath for one hour, cooled, poured to ice water (100 ml)
and neutralized with dilute hydrochloric acid (4N) the resultant solid,

1506
M. Raghavendra et al.
2-seleno-3-formyl quinoline obtained was filtered, washed with water
(300 ml) dried and recrystallized from alcohol.
Yield: IR (KBr) cm−1 3150–3300 (tautomeric form of -NH, SeH), 1650
1
(CHO) 1180 (C Se). H NMR (400 MHz, DMSO-d6) 5.8 (tautomeric
form of -NH, SeH), 10.35 (-CHO), 7.25–8.35 (m, 5H, Ar-H). MS m/z: 236
(M+).
2-Seleno-6-methylquinoline-3-carbaldehyde (2b)
Prepared from methyl derivative of quinoline 1b.
IR (KBr) cm−1 3155–3310 (tautomeric form of NH, SeH), 1650
1
(CHO) 1180 (C Se). H NMR (400 MHz, DMSO-d6) 2.60 (3H, s, CH3),
5.85 (tautomeric form of NH, SeH), 10.35 ( CHO) 7.20–8.30 (m, 4H,
Ar-H). MS m/z: 250 (M+).
2-Seleno-6-methoxy-3-carbaldehyde (2c)
Prepared from methoxy derivative of quinoline 1c.
IR (KBr) cm−1 3160–3300 tautomeric form of ( NH, SeH) 1650
(CHO) 1180 (C Se). 1H NMR (400 MHz, DMSO-d6) 3.95 (3H, s, OCH3),
5.90 (tautomeric form of NH, SeH), 10.40 ( CHO) 7.35–8.40 (m, 4H,
Ar H). MS, m/z 266 (M+).
2-Seleno-7-methylquinoline-3-carbaldehyde (2d)
Prepared from methyl derivative of quinoline 1d.
IR (KBr) cm−1 3155–3310 (tautomeric form of NH, SeH), 1650
1
(CHO) 1182 (C Se). H NMR (400 MHz, DMSO-d6) 2.65 (3H, s, CH3),
5.85 (tautomeric form of NH, SeH), 10.35 ( CHO) 7.25–8.37 (m, 4H,
Ar H). MS m/z: 250 (M+).
General Procedure: Synthesis
1-Selenolo[2,3-b]quinolin-2-ylethanone
A mixture of 2a (2.360 g, 10 mmol), phenacyl bromide (1.99 g, 10 mmol)
and potassium carbonate (1.380 g, 20 mmol) were ground for uniform
mixing. The mixture was then subjected to microwave radiation in a
domestic microwave oven for 8 min at an interval of 1 min at 160 W
as required to complete the reaction (TLC). The reaction mixture was
then poured into water, stirred, filtered and dried. The crude product
was recrystallized from aqueous DMF to give 2.990 g (89%) of 3a. All
the other compounds were prepared in a similar way with 85–88% yield.

Novel Selenolo[2,3-b]quinoline Derivatives
1507
Selenolo[2,3-b]quinolin-2-yl(phenyl)methanone (3a)
Prepared according to the general method of preparation.
Solid; (89%), MS, m/z 336 (M+); IR (KBr) (cm−1): 1640 (CO), 1H NMR
(400 MHz) (DMSO-d6) (δ) ppm: 8.52 (s, C3-H), 8.25 (s, C4-H), 7.50–8.16
(9H, m, Ar-H).
(6-Methylselenolo[2,3-b]quinolin-2-yl)(phenyl)methanone (3b)
Prepared according to the general method of preparation.
Solid; (88%), MS, m/z 350 (M+); IR (KBr) (cm−1): 1643 (CO), 1H NMR
(400 MHz) (DMSO-d6) (δ) ppm: 2.45 (3H, s, Ar-CH3), 8.58 (s, C3-H), 8.24
(s, C4-H), 7.55–8.13 (8H, m, Ar-H).
(6-Methoxyselenolo[2,3-b]quinolin-2-yl)(phenyl)methanone
(3c)
Prepared according to the general method of preparation.
Solid; (85%), MS, m/z 366 (M+); IR (KBr) (cm−1): 1640 (CO), 1H NMR
(400 MHz) (DMSO-d6) (δ) ppm: 3.95 (3H, s, Ar-OCH3), 8.60 (s, C3-H),
8.24 (s, C4-H), 7.58–8.12 (8H, m, Ar-H).
(6-Methylselenolo[2,3-b]quinolin-2-yl)(phenyl)methanone (3d)
Prepared according to the general method of preparation.
Solid; (88%), MS, m/z 350 (M+); IR (KBr) (cm−1): 1645 (CO), 1H NMR
(400 MHz) (DMSO-d6) (δ) ppm: 2.47 (3H, s, Ar-CH3), 8.58 (s, C3-H), 8.26
(s, C4-H), 7.55–8.15 (8H, m, Ar-H).
Selenolo[2,3-b]quinoline-2-carboxamide (4a)
Prepared according to the general method of preparation.
Solid; (89%), MS, m/z 275 (M+); IR (KBr) (cm−1): 3350-3175
1
(CONH2), 1630 (CO). H NMR (400 MHz) (DMSO-d6) (δ) ppm: 7.42
(2H, b s, CONH2), 8.50 (s, C3-H), 8.20 (s, C4-H), 7.54–8.05 (4H, m, Ar-
H).
6-Methylselenolo[2,3-b]quinoline-2-carboxamide (4b)
Prepared according to the general method of preparation.
Solid; (90%), MS, m/z 289 (M+); IR (KBr) (cm−1): 3360–3185
1
(CONH2), 1625 (CO). H NMR (400 MHz) (DMSO-d6) (δ) ppm: 2.40

1508
M. Raghavendra et al.
(3H, s, Ar-CH3), 7.42(2H, b s, CONH2) 8.56 (s, C3-H), 8.25 (s, C4-H),
7.62– 8.12 (3H, m, Ar-H).
6-Methoxyselenolo[2,3-b]quinoline-2-carboxamide (4c)
Prepared according to the general method of preparation.
Solid; (88%), MS, m/z 305 (M+); IR (KBr) (cm−1): 3360–3190
1
(CONH2), 1625 (CO). H NMR (400 MHz) (DMSO-d6) (δ) ppm: 3.90
(3H, s, Ar-OCH3), 7.45(2H, b s, CONH2) 8.53 (s, C3-H), 8.26 (s, C4-H),
7.65–8.14 (3H, m, Ar-H).
6-Methylselenolo[2,3-b]quinoline-2-carboxamide (4d)
Prepared according to the general method of preparation.
Solid; (90%), MS, m/z 289 (M+); IR (KBr) (cm−1): 3370–3195
1
(CONH2), 1630 (CO). H NMR (400 MHz) (DMSO-d6) (δ) ppm: 2.45
(3H, s, Ar-CH3), 7.40(2H, b s, CONH2) 8.60 (s, C3-H), 8.25 (s, C4-H),
7.62–8.15 (3H, m, Ar-H).
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