Synthesis of 2-benzoylfuro[2,3-b[quinolines from quinoline-based chalcones

Article abstract of DOI:10.1080/00397911.2011.555902

We have described an elegant synthesis of 2-benzoylfuro[2,3-b]quinolines from quinolinyl chalcones via bromination and epoxidation. Interestingly, we found that during the bromination, the chalcones were cyclized to gave monobromodihydrofuroquinolines, wh

Full text of DOI:10.1080/00397911.2011.555902

This article was downloaded by: [Georgetown University]
On: 27 August 2013, At: 20:53
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of 2-Benzoylfuro[2,3-
b]Quinolines from Quinoline-Based
Chalcones
Devadoss Karthik Kumar a & Subramaniam Parameswaran Rajendran
a
a Department of Chemistry, School of Chemical Sciences, Bharathiar
University, Coimbatore, Tamilnadu, India
Accepted author version posted online: 20 Dec 2011.Published
online: 09 Apr 2012.
To cite this article: Devadoss Karthik Kumar & Subramaniam Parameswaran Rajendran (2012)
Synthesis of 2-Benzoylfuro[2,3-b]Quinolines from Quinoline-Based Chalcones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
42:15, 2290-2298, DOI: 10.1080/00397911.2011.555902
To link to this article: http://dx.doi.org/10.1080/00397911.2011.555902
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 42: 2290–2298, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.555902
SYNTHESIS OF 2-BENZOYLFURO[2,3-b]QUINOLINES
FROM QUINOLINE-BASED CHALCONES
Devadoss Karthik Kumar and Subramaniam Parameswaran
Rajendran
Department of Chemistry, School of Chemical Sciences,
Bharathiar University, Coimbatore, Tamilnadu, India
GRAPHICAL ABSTRACT
Abstract We have described an elegant synthesis of 2-benzoylfuro[2,3-b]quinolines from
quinolinyl chalcones via bromination and epoxidation. Interestingly, we found that during
the bromination, the chalcones were cyclized to gave monobromodihydrofuroquinolines,
which were dehydrobrominated with 1,8-diazabicyclo[5,4,0]undec-7-ene. During the epox-
idation, chalcones were not cyclized and gave epoxides, which were treated with polypho-
sphoric acid to give the title compound. We have differentiated the addition of bromine
and urea hydrogen peroxide to a,b-unsaturated carbonyl of quinolinyl chalcones by this
new mechanism.
Keywords Bromocyclization; furoquinolines; Michael addition; quinolinyl chalcone;
UHP
INTRODUCTION
Heterocyclic compounds have fascinating chemical behavior as well as
inevitable pharmacological properties. In particular, furo[2,3-b]quinolines are
ubiquitous heterocycles in natural products and pharmaceuticals. Furoquinoline
alkaloids are mainly isolated from Rutaceae and Solanaceae plant species,[1] and they
show significant biological activities, which include vasoconstructive, antidiuretic,
antiarrhythmic, spamolytic, sedative, and hypothermal effects;[2] antitumaral,
Received September 15, 2010.
Address correspondence to Devadoss Karthik Kumar or Subramaniam Parameswaran Rajendran,
Department of Chemistry, School of Chemical Sciences, Bharathiar University, Coimbatore 641 046,
Tamilnadu, India. E-mail: dskarthik06@gmail.com; rajendransp@yahoo.com
2290

2-BENZOYLFURO[2,3-b]QUINOLINES
2291
antipyretic, antiplatelet, and cytotoxic activities, and photosensitization for DNA
damage and mutation.[3] Because of such a wide range of biological activities,
increasing attention has been directed to the synthesis of furoquinoline derivatives
and alkaloids.
The methods we report herewith are for the synthesis of 2-benzoylfuro[2,3-
b]quinolines using series of chalcones. It is well known that chalcones serve as the
backbone of many natural products and analogs. A wide range of heterocycles
can be generated from the chalcone type of compounds. However, chalcones are
not only good synthetic intermediates, they also serve as good pharmacophores.
Owing to the relevant biological activities including antimicrobial, antibacterial,
antifungal, antimalarial,[4] anticancer,[5] and cytotoxic activities,[6] the synthesis of
novel chalcones is a rewarding research area.
RESULTS AND DISCUSSION
To the best of our knowledge, hitherto only one report is available in the
literature for the synthesis of 2-benzoylfuro[2,3-b]quinolines by the Rap–Stoermer
reaction using microwaves, and it reports only a few derivatives.[7] Therefore, a gen-
eral and conventional method for the synthesis of 2-benzoylfuro[2,3-b]quinolines
with good yields from new intermediates will be attractive in heterocyclic chemistry.
The current process presents novel and elegant methods to synthesize of 2-benzoyl-
furo[2,3-b]quinolines. To achieve the targeted compounds 5a–e, we synthesized chal-
cones as an intermediate from 3-formylquinolones[8–10] 1a–e and acetophenone by
the Claisen–Schmidt condensation reaction. The final compounds 5a–e were
obtained by two different methods from the chalcones via bromination and
epoxidation.
First, the chalcones were brominated at room temperature. The bromination
reaction still remains very appealing because of the diverse chemical behavior of
bromine. Interestingly, we found that during this bromination, the chalcones 2a–e
were cyclized to give cis-2-benzoyl-3-bromo-2,3-dihydrofuro[2,3-b]quinolines 3a–e
without adding any base. The cis configuration of the compounds 3a–e was con-
firmed by the coupling constant between H-2 and H-3, J ¼ 8.5 Hz (compound 3c),
in its NMR spectrum.[11,12] We expected the dibromo compound of the chalcones.
However, in contrast to our expectations we got only monobromo compounds
rather then dibromo compounds because of intramolecular cyclization. Further-
more, the bromination reactions were carried out in a mixture of solvents (chloro-
form and acetic acid). Initially, we took chloroform only but the yield of the
reactions was less (about 40%) and the reaction time was 6 to 8 h. Even with pro-
longed stirring, the spot of starting material did not disappear completely in
thin-layer chromatography (TLC). This may be due to the low solubility of chal-
cones in chloroform. When we added acetic acid to the reaction medium, we found
that the reactions were completed within 2–3 h with the spot of starting compounds
completely disappearing in TLC, and also the yield of the reactions was substantially
increased (74–84%). This might be due to complete solubility of chalcones in a mix-
ture of solvents (i.e., chloroform and acetic acid). Here the acetic acid also acts as a
catalyst for this reaction because the reaction time was also reduced. Based on the
current findings, we report a novel mechanism for this reaction (Fig. 1).

2292
D. K. KUMAR AND S. P. RAJENDRAN
Figure 1. Proposed mechanism for bromocyclization.
The addition of bromine to quinolinyl chalcones follows acid-catalyzed
Michael type of addition reaction to form brominium ion and then intramolecular
cyclization without adding base. Here, the eliminated bromine (Brꢀ) ion abstracts
proton from quinoline ring and promotes (like bromodecarboxylation[13]) the intra-
molecular cyclization. After that, the monobromo compounds were dehydrohalo-
gented by refluxing with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) in dioxane.
Next, the chalcones were epoxidized. It is very difficult to isolate the epoxide of
this type of heterocyclic compounds because intramolecular cyclization takes place
predominantly. However, we isolated the epoxide of these compounds 4a–e by using
chalcones 2a–e and urea hydrogen peroxide adduct. Only few a papers in the litera-
ture report the oxidation of a,b-unsaturated carbonyl compounds with UHP, which
was freshly prepared from urea and 33% hydrogen peroxide.[14]
This reaction was carried out in methanol and potassium carbonate. Here the
potassium carbonate was used for generating ꢀOOH from urea hydrogen peroxide
adduct and it does not assist the intramolecular cyclization of epoxides because
the epoxides 4a–e were not cyclized in this reaction. We have isolated the epoxides
and characterized them by spectroscopic data; the 1H NMR shows that the coupling
constant (J) of Ha and Hb of the compound 4c is 2.0 Hz. Finally, the epoxides 4a–e
were cleaved and dehydrated simultaneously by refluxing with polyphosphoric acid
(PPA) to furnish the corresponding 2-benzoylfuro[2,3-b]quinolines.
Bromination and epoxidation both follow the Michael type of addition reac-
tion. During the bromination, the chalcones were cyclized, but during the epoxida-
tion the chalcones were not cyclized. This may be explained by considering the
structure of urea hydrogen peroxide.[15] In urea hydrogen peroxide, adduct hydrogen
bonding plays a crucial role (i.e., hydrogen peroxide strongly hydrogen bonded with
urea). Owing to this, the eliminated hydroxide ion (OHꢀ) could not promote the
intramolecular cyclization; i.e., the hydroxide ion (OHꢀ) was not freely available
for abstracting a proton from the quinoline ring, so the chalcones were not cyclized

2-BENZOYLFURO[2,3-b]QUINOLINES
2293
Scheme 1. Reagents and conditions; (i) CH3COC6H5, CH3OH-KOH; (ii) Br2, CHCl3, CH3COOH; (iii)
DBU, 1,4- dioxane; (iv) UHP, K2CO3; and (v) PPA.
Table 1. Synthesis of 2-benzoylfuro[2,3-b]quinolines
Conditions
Yield (%)
Entry Product From compound 3 From compound 4 From compound 3 From compound 4
1
2
3
4
5
5a
5b
5c
5d
5e
101 ꢁC=8 h
101 ꢁC=8 h
101 ꢁC=8 h
101 ꢁC=8 h
101 ꢁC=8 h
140 ꢁC=6 h
140 ꢁC=6 h
140 ꢁC=6 h
140 ꢁC=6 h
140 ꢁC=6 h
75
78
76
79
72
57
62
58
61
55
and we got epoxide 4a–e compounds. The whole of the reaction strategy was
summarized in Scheme 1, and the results are discussed in Table 1.
CONCLUSION
In conclusion, two novel and convenient methods for the synthesis of
2-benzoylfuro[2,3-b]quinolines have been developed using chalcones by bromocycli-
zation and epoxidation. Amusingly, during the bromination the chalcones were
cyclized without adding base, and during the epoxidation the chalcones were not
cyclized even though a mild base was present in this reaction. We differentiated these
reactions and the proposed mechanisms.

2294
D. K. KUMAR AND S. P. RAJENDRAN
EXPERIMENTAL
Melting points were determined using a Raga melting-point apparatus and
were uncorrected. Infrared (IR) spectra were recorded on a Shimadzu Fourier trans-
form (FT) IR PC (S) 8201 spectrometer using KBr pellets, and the absorption fre-
quencies are expressed in reciprocal centimeters (cmꢀ1). NMR spectra were taken
on Bruker 400 MHz and 500 MHz spectrometers using tetramethylsilane (TMS) as
an internal reference. The chemical shifts were expressed in parts per million
(ppm). The mass spectra were determined on an Autospec EIþ mass spectrometer
and high-resolution mass spectrometer (electrospray ionization) [HRMS (ESI)].
Elemental analyses were performed on a Vario EL IIICHNS analyzer and
Perkin-Elmer analyzer.
3-(3-Oxo-3-phenyl-propenyl)-1H-quinolin-2-one (2a–e)
A mixture of compound 1 (1c, 1.87 g, 0.01 mol) and acetophenone (1.16 ml,
0.01 mol) in methanolic KOH was stirred until the starting material was disappeared
(about 12 h). After that, the mixture was poured into crushed ice and then neutra-
lized with 1:1 HCl. The precipitate was filtered off, dried, and then chromatographed
over silicagel using a mixture of ethyl acetate and petroleum ether as eluent to give 2
as yellow solid.
7-Methyl-3-(3-oxo-3-phenyl-propenyl)-1H-quinolin-2-one
.
(2c). Yield:
93%, mp 282 ꢁC. IR (KBr): 1654, 1590 cmꢀ1 1H NMR (500 MHz; DMSO-d6):
d ¼ 2.41 (s, 3H, CH3), 7.15 (s, 1H, C8H), 7.79 (d, 1H, J ¼ 15.5 Hz, Hb), 8.28 (d,
1H, Ha), 8.57 (s, 1H, C4H), 7.08–8.07 (m, 8H, ArH), 12.02 (s, 1H, NH). 13C NMR
(100 MHz; DMSO-d6): d ¼ 22.6, 119.1, 122.1, 123.5, 123.8, 125.5, 126.8, 128.2, 128.8,
133.0, 137.4, 137.6, 138.7, 141.5, 161.3, 189.8. HRMS (ESI) calcd. for C19H15NO2
(M þNa) 312.1000: found 312.1001.
3-(3-Oxo-3-phenyl-propenyl)-1H-quinolin-2-one (2a). Yield: 88%; mp
1
236 ꢁC. IR (KBr): 1669, 1586 cmꢀ1. H NMR (500 MHz; DMSO-d6): d ¼ 7.24 (t,
1H, J ¼ 7.5, C7H), 7.36 (d, 1H, C8H, J ¼ 8 Hz), 7.81 (d, 1H, J ¼ 16 Hz, Hb), 8.31
(d, 1H, Ha), 8.63 (s, 1H, C4H), 7.57–7.08 (m, 7H, ArH), 12.09 (s, 1H, NH). Anal.
calcd. for C18H13NO2: C, 78.53; H, 4.76; N, 5.09. Found: C, 79.00; H, 4.86; N, 4.98.
6-Methyl-3-(3-oxo-3-phenyl-propenyl)-1H-quinolin-2-one
.
(2b). Yield:
90%; mp 245 ꢁC. IR (KBr): 1668, 1594 cmꢀ1 1H NMR (400 MHz; DMSO-d6):
d ¼ 2.45 (s, 3H, CH3), 7.14–87.7 (m, 5H, ArH), 7.82 (d, 1H, J ¼ 15.6 Hz, Hb), 8.09
(d, 1H, J ¼ 8.4 Hz, C8H), 8.25 (d, 1H, Ha), 8.06 (s, 1H, C5H), 8.63 (s, 1H, C4H),
11.20 (s, 1H, NH). Anal. calcd. for C19H15NO2: C, 78.87; H, 5.23; N, 4.84. Found:
C, 78.75; H, 5.16; N, 4.95.
8-Methyl-3-(3-oxo-3-phenyl-propenyl)-1H-quinolin-2-one
.
(2d). Yield:
95%; mp 252 ꢁC. IR (KBr): 1656, 1573 cmꢀ1 1H NMR (500 MHz; DMSO-d6):
d ¼ 2.50 (s, 3H, CH3), 7.15 (s, 1H, C6H), 7.42 (d, 1H, C5H), 7.84 (d, 1H, J ¼ 16 Hz,
Hz, Hb), 8.07 (d, 1H, J ¼ 7 Hz, C7H), 8.27 (d, 1H, Ha), 8.65 (s, 1H, C4H), 7.08–8.07
(m, 8H, ArH), 11.22 (s, 1H, NH). Anal. calcd. for C19H15NO2: C, 78.87; H, 5.23; N,
4.84. Found: C, 79.01; H, 5.30; N, 4.86.

2-BENZOYLFURO[2,3-b]QUINOLINES
2295
6-Methoxy-3-(3-oxo-3-phenyl-propenyl)-1H-quinolin-2-one (2e). Yield:
89%; mp 275 ꢁC. IR (KBr): 1665, 1580 cmꢀ1 1H NMR (500 MHz; DMSO-d6):
.
d ¼ 3.90 (s, 3H, OCH3), 7.78 (s, 1H, C5H), 7.80 (d, 1H, J ¼ 15.5 Hz, Hb), 7.90 (d,
1H, J ¼ 7.5, C7H), 8.00 (d, 1H, J ¼ 7.5, C8H), 8.04 (s, 1H, C4H), 8.55 (d, 1H, Ha),
7.05–8.13 (m, 5H, ArH), 12.02 (s, 1H, NH). Anal. calcd. for C19H15NO3: C,
74.74; H, 4.95; N, 4.59. Found: C, 74.35; H, 5.07; N, 4.92.
3-Bromo-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-methanone
(3a–e)
Bromine was added slowly to a stirred solution of compound 2 (2c, 1.445 g,
0.005 mol) in chloroform acetic acid mixture. After completion of the reaction, which
was checked by TLC, the excess of bromine was removed by adding 25% solution of
sodium sulfite through the dropping funnel. The colorless chloroform layer was
separated out, washed with water, and dried over magnesium sulfate. After a few
minutes, the magnesium sulfate was removed by filtration. The solution was evapo-
rated to dryness to give 3, which was purified by column chromatography using pet-
roleum ether and ethyl acetate as eluent.
3-Bromo-7-methyl-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-methanone
(3c). Yield: 82%; mp 160 ꢁC. IR (KBr): 1638 cmꢀ1. 1H NMR (500 MHz; DMSO-d6):
d ¼ 2.62 (s, 3H, CH3), 7.77 (d, 1H, J ¼ 8.5 Hz, C3H), 8.032 (s, 1H, C8H), 8.25 (d, 1H,
C2H), 8.49 (s, 1H, C4H), 7.50–8.56 (m, 7H, ArH). 13C NMR (100 MHz; DMSO-d6):
d ¼ 23.7, 113.5, 119.5, 123.0, 126.2, 127.6, 128.64, 129.35, 129.99, 130.77, 131.17,
133.42, 132.37, 136.16, 140.79, 146.08, 161.53, 183.55 MS: m=z ¼ 368 (Mþ), 288
(M-Br)þ. Anal. calcd. for C19H14NO2Br: C, 61.97; H, 3.83; N, 3.80. Found: C,
61.99; H, 3.92; N, 3.76.
3-Bromo-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-methanone (3a).
1
Yield: 78%; mp 174 ꢁC. IR (KBr): 1633 cmꢀ1. H NMR (500 MHz; DMSO-d6):
d ¼ 8.00 (d, 1H, J ¼ 8.8 Hz, C3H), 8.16 (d, 1H, C2H), 8.61 (s, 1H, C4H), 7.55–8.27
(m, 9H, ArH). Anal. calcd. for C18H12NO2Br: C, 61.04; H, 3.41; N, 3.95. Found:
C, 60.85; H, 3.58; N, 4.10.
3-Bromo-6-methyl-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-methanone
(3b). Yield: 87%; mp 171 ꢁC. IR (KBr): 1640 cmꢀ1. 1H NMR (500 MHz; DMSO-d6):
d ¼ 2.61 (s, 3H, CH3), 7.40 (d, 1H, J ¼ 8.4 Hz, C7H), 7.88 (d, 1H, J ¼ 8.5 Hz, C3H),
7.9 (s,1H, C5H), 8.15 (d, 1H, C8H), 8.24 (d, 1H, C2H), 8.55 (s, 1H, C4H), 7.51–7.71
(m, 5H, ArH). Anal. calcd. for C19H14NO2Br: C, 61.97; H, 3.83; N, 3.80. Found: C,
61.75; H, 4.02; N, 4.00.
3-Bromo-8-methyl-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-methanone
(3d). Yield: 85%; mp 186 ꢁC. IR (KBr): 1648 cmꢀ1. 1H NMR (400 MHz; DMSO-d6):
d ¼ 2.87 (s, 3H, CH3), 7.84 (d, 1H, J ¼ 8.2 Hz, C3H), 8.20 (d, 1H, C2H), 8.58 (s, 1H,
C4H), 7.45–8.22 (m, 8H, ArH). Anal. calcd. for C19H14NO2Br: C, 61.97; H, 3.83; N,
3.80. Found: C, 61.86; H, 4.02; N, 3.78.
3-Bromo-6-methoxy-2,3-dihydrofuro[2,3-b]quinolin-2-yl-phenyl-metha-
none (3e). Yield: 74%; mp 196 ꢁC. IR (KBr): 1645 cmꢀ1 1H NMR (500 MHz;
.

2296
D. K. KUMAR AND S. P. RAJENDRAN
DMSO-d6): d ¼ 3.79 (s, 3H, OCH3), 7.42 (d, 1H, J ¼ 8.2 Hz, C7H), 7.87 (d, 1H,
J ¼ 8.4 Hz, C3H), 7.90 (s, 1H, C5H), 8.15 (d, 1H, J ¼ 8.2 Hz, C8H), 8.25 (d, 1H,
C2H), 8.56 (s, 1H, C4H), 7.49–7.73 (m, 5H, ArH). Anal. calcd. for C19H14NO3Br:
C, 59.39; H, 3.67; N, 3.65. Found: C, 59.30; H, 3.87; N, 3.93.
3-(3-Benzoyl-oxiranyl)-1H-quinolin-2-one (4a–e)
A mixture of compound 2 (2c, 1.445 g, 0.005 mol) in methanol and potassium
carbonate and urea hydrogen peroxide (UHP) (2 to 3 mol extra) was stirred for 2 h.
After completion of the reaction, which was checked by TLC, the mixture was poured
into crushed ice. The precipitate was filtered off, dried, and column chromatographed
over silica gel using petroleum ether and ethyl acetate as eluent to give compound 4.
3-(3-Benzoyl-oxiranyl)-7-methyl-1H-quinolin-2-one (4c). Yield 79%; mp
1
205 ꢁC. IR (KBr): 1651, 1577 cmꢀ1. H NMR (400 MHz; DMSO-d6): d ¼ 2.34 (s,
3H, CH3), 4.11 (d, 1H, J ¼ 2.0 Hz, Hb), 4.73 (d, 1H, Ha), 7.51 (s, 1H, C8H), 7.80
(s, 1H, C4H), 7.23–8.10 (m, 7H, ArH), 11.93 (s, 1H, NH). 13C NMR (125 MHz;
DMSO-d6): d ¼ 20.3, 55.2, 58.8, 114.9, 118.5, 127.4, 127.5, 128.2, 128.9, 131.1,
131.9, 134.0, 135.1, 136.2, 161.0. HRMS (ESI) calcd. for C19H15NO3 (M þ Na)
328.0950, Found 328.0956.
3-(3-Benzoyl-oxiranyl)-1H-quinolin-2-one (4a). Yield 85%; mp 196 ꢁC. IR
(KBr): 1648, 1570 cmꢀ1
J ¼ 2.4 Hz, Hb), 4.75 (d, 1H, Ha), 7.82 (s, 1H, C4H), 7.13–8.12 (m, 9H, ArH),
12.01 (s, 1H, NH). Anal. calcd. for C18H13NO3: C, 74.22; H, 4.50; N, 4.81. Found:
C, 74.25; H, 4.43; N, 4.60.
.
1H NMR (500 MHz; DMSO-d6): d ¼ 4.10 (d, 1H,
3-(3-Benzoyl-oxiranyl)-6-methyl-1H-quinolin-2-one (4b). Yield 88%; mp
1
235 ꢁC. IR (KBr): 1645, 1567 cmꢀ1. H NMR (500 MHz; DMSO-d6): d ¼ 2.38 (s,
3H, CH3), 4.09 (d, 1H, J ¼ 2.5 Hz, Hb), 4.74 (d, 1H, Ha), 7.13 (s, 1H, C5H), 7.84
(s, 1H, C4H), 7.05–8.09 (m, 7H, ArH), 11.94 (s, 1H, NH). Anal. calcd. for
C19H15NO3: C, 74.74; H, 4.95; N, 4.59. Found: C, 74.84; H, 4.97; N, 4.48.
3-(3-Benzoyl-oxiranyl)-8-methyl-1H-quinolin-2-one (4d). Yield 83%; mp
1
217 ꢁC. IR (KBr): 1657, 1581 cmꢀ1. H NMR (500 MHz; DMSO-d6): d ¼ 2.89 (s,
3H, CH3), 4.13 (d, 1H, J ¼ 2.2 Hz, Hb), 4.72 (d, 1H, Ha), 7.85 (s, 1H, C4H),
7.18–8.18 (m, 8H, ArH), 11.93 (s, 1H, NH). Anal. calcd. for C19H15NO3: C,
74.74; H, 4.95; N, 4.59. Found: C, 74.76; H, 4.89; N, 4.65.
3-(3-Benzoyl-oxiranyl)-6-methoxy-1H-quinolin-2-one (4e). Yield 72%;
1
mp 247 ꢁC. IR (KBr): 1654, 1573 cmꢀ1. H NMR (500 MHz; DMSO-d6): d ¼ 3.80
(s, 3H, OCH3), 4.12 (d, 1H, J ¼ 2.3 Hz, Hb), 4.72 (d, 1H, Ha), 7.42 (s, 1H, C5H),
7.83 (s, 1H, C4H), 7.11–8.08 (m, 7H, ArH), 11.93 (s, 1H, NH). Anal. calcd. for
C19H15NO4: C, 71.02; H, 4.71; N, 4.36. Found: C, 69.95; H, 4.53; N, 4.39.
Furo[2,3-b]quinolin-2-yl-phenyl-methanone (5a–e)
From compound 3. A mixture of compound 3 (3c, 0.736 g, 0.002 mol) and
DBU (0.448 ml, 0.003 mol) was refluxed in 1,4-dioxane for 6 h. After completion

2-BENZOYLFURO[2,3-b]QUINOLINES
2297
of the reaction, the mixture was poured onto crushed ice. The precipitate was filtered
off, dried, and column chromatographed over silica gel using petroleum ether and
ethyl acetate as eluent to give 5.
From compound 4. The compound 4 (4c, 0.915 g, 0.003 mol) was heated with
PPA at 140 ꢁC for 6 h. After completion of the reaction, which was checked by TLC,
the mixture was poured onto crushed ice. The precipitate was filtered off, dried, and
column chromatographed over silica gel using petroleum ether and ethyl acetate as
eluent.
7-Methylfuro[2,3-b]quinolin-2-yl-phenyl-methanone (5c). Yields 76 aꢀn1d
58% (from compounds 3c and 4c respectively); mp 176 ꢁC. IR (KBr): 1644 cm
.
1H NMR (400 MHz; DMSO-d6): d ¼ 2.57 (s, 3H, CH3), 7.47–8.11 (m, 7H, ArH),
7.86 (s, 1H, C8H), 7.92 (s, 1H, C4H), 8.90 (s, 1H, C3H). 13C NMR (100 MHz;
DMSO-d6): d ¼ 21.5, 115.8, 118.7, 124.6, 126.7, 127.6, 128.5, 128.7, 129.2, 133.3,
133.7, 136.3, 141.0, 146.6, 151.4, 160.9. Anal. calcd. for C19H13NO2: C, 79.43; H,
4.56; N, 4.88. Found: C, 79.45; H, 4.58; N, 4.98.
8-Methylfuro[2,3-b]quinolin-2-yl-phenyl-methanone (5d). Yields 79 aꢀn1d
61% (from compounds 3d and 4d respectively); mp 146 ꢁC. IR (KBr): 1633 cm
.
1H NMR (400 MHz; DMSO-d6): d ¼ 2.87 (s, 3H, CH3), 7.45–8.22 (m, 8H, ArH),
7.69 (s, 1H, C4H), 8.58 (s, 1H, C3H). Anal. calcd. for C19H13NO2: C, 79.43; H,
4.56; N, 4.88. Found: C, 79.52; H, 4.53; N, 4.82.
The 5a, 5b, and 5e derivative’s spectroscopic data are consistent with those
reported in the literature.[7]
ACKNOWLEDGMENTS
We are grateful to the NMR research center, IISC, Bangalore; Sophisticated
Analytical Instrument Facility, Indian Institute of Technology, Madras; and the
Indian Institute of Chemical Technology, Hyderabad, for providing spectral and
analytical facilities.
REFERENCES
1. (a) Michael, J. P. Quinoline, quinazoline, and acridone alkaloids. Nat. Prod. Rep. 2003,
20, 476–493; (b) Michael, J. P. Quinoline, quinazoline, and acridone alkaloids. Nat. Prod.
Rep. 2004, 21, 650–668; (c) Michael, J. P. Quinoline, quinazoline, and acridone alkaloids.
Nat. Prod. Rep. 2008, 25, 166–187.
2. Pirrung, M. C.; Blume, F. Rhodium-mediated dipolar cycloaddition of diazoquinoline-
diones. J. Org. Chem. 1999, 64, 3642–3649.
3. Barluenga, J.; Mendoza, A.; Rodriguez, F.; Fananas, F. J. Synthesis of furoquinolines by
a one-pot multicomponent cascade reaction catalyzed by platinum complexes. Chem. Eur.
J. 2008, 14, 10892–10895.
4. Katritzky, A. R.; Rees, C. W. Comprehensive Hetrocyclic Chemistry; Pergamon Press:
Oxford, 1984; 25–85.
5. (a) Reziq, R.; Chebah, M.; Rhouati, S.; Duck, S.; Lawrence, N. J. Synthesis of some qui-
nolinyl acyl a,b-unsaturated ketones. J. Soc. Alger. Chem. 2000, 10, 111–120; (b) Ducki,
S.; Hadfield, J. A.; Lawrence, N. J.; Liu, C. Y.; Mc Gown, A. T.; Zang, X. X. Isolation of

2298
D. K. KUMAR AND S. P. RAJENDRAN
E-(40-hydroxyphenyl-but-1-en-3-one from scutellaria barbata. Planta Medica 1996, 62,
185–186.
6. Moussaoui, F.; Belfaitah, A.; Debache, A.; Rhouati, S. Synthesis and characterization of
some aryl quinolinyl a,b-unsaturated ketones. J. Soc. Alger. Chim. 2002, 12, 71–78.
7. Raghavendra, V.; Halehatty, S.; Bhojya, N.; Sherigara, B. S. Microwave-assisted one-pot
synthesis of some new furo[2,3-b]quinolines using potassium carbonate under solvent-free
conditions. Can. J. Chem. 2007, 85, 1041–1044.
8. Meth-Cohn, O.; Narine, B.; Tarnowski, B. A versatile new synthesis of quinolines and
related fused pyridines, part 5: The synthesis of 2-chloroquinoline-3-carbaldehydes.
J. Chem. Soc., Perkin Trans. 1 1981, 1520–1530.
9. Meth-Cohn, O.; Narine, B.; Tarnowski, B. A versatile new synthesis of quinolines and
related fused pyridines, part 9: Synthetic application of the 2-chloroquinoline-3-
carbaldehydes. J. Chem. Soc., Perkin Trans. 1 1981, 2509–2517.
10. Mrityunjay, K. S.; Radhey, M. S. Synthesis of diastereomeric 2,4-disubstituted
pyrano[2,3-b]quinolines from 3-formyl-2-quinolones through O–C bond formation via
intramolecular electrophilic cyclization. Tetrahedron Lett. 2007, 48, 5987–5990.
11. Kazuhiro, Y.; Shinji, T.; Fumio, T.; Ingeborg, C. Preparative and mechanistic studies of
solvent–free Rap-Stoermer reactions. Green Chem. 2003, 5, 353–356.
12. Shunsaku, S.; Hiroyuki, M.; Masatoshi, I.; Toshimasa, I.; Yoichi, I.; Akiko, I. Furopyr-
idines, II: Bromination and nitration of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]-, furo[3,2-
c]pyridine. J. Heterocyclic Chem. 1984, 21, 725.
13. Huang, Y.; Cheng, Y.; Hsien, K.; Chen, Y.; Kao, C. Concise bromodecarboxylation of
cinnamic acids to b-bromostyrenes. Tetrahedron Lett. 2009, 50, 1834–1837.
14. (a) Copper, M. S.; Heaney, H.; Newbold, A. J.; Sanderson, W. R. Oxidation reactions
using urea–hydrogen peroxide: A safe alternative to anhydrous hydrogen peroxide.
Synlett. 1990, 533; (b) Fan, C. L.; Lee, W. D.; Teng, N. W.; Sun, Y. C.; Chen, K. Epox-
idation of chiral camphor N-enoylpyrazolidinones with methyl(trifluoromethyl)dioxirane
and urea hydrogen peroxide=acid anhydride: Reversal of stereoselectivity. J. Org. Chem.
2003, 68, 9816–9818.
15. Dobado, J. A.; Molina, J.; Portal, D. Theoretical study on the urea–hydrogen peroxide 1:1
complexes. J. Phys. Chem. A 1998, 102, 778–784.