Unusual product from condensative cyclization: Pyrano[3,2-f]quinolin-3,10- diones from 6-amino-5-[(trimethylsilyl)ethynyl]-2 H-chromen-2-one and aryl aldehydes

Article abstract of DOI:10.1055/s-0029-1219378

A new efficient and simple route for the synthesis of 8,9-dihydro-3H- pyrano[3,2-f]quinoline-3,10(7H)-dione derivatives has been accomplished via sulfuric acid promoted condensation--cyclization of 6-amino-5-[(trimethylsilyl) ethynyl]-2H-chromen-2-one and aromatic aldehydes. The products can be oxidized to the corresponding 10-methoxy-8-aryl-3H-pyrano[3,2-f]quinolin-3-one derivatives by FeCl₃6H₂O in methanol. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0029-1219378

LETTER
735
Unusual Product from Condensative Cyclization: Pyrano[3,2-f]quinolin-3,10-
diones from 6-Amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one and Aryl
Aldehydes
S
ynthesis of Pyran
.
o[3,2-
f
]quino
C
lin-3,10-dione
D
.
e
rivatives Majumdar,* Abu Taher, Sudipta Ponra
Department of Chemistry, University of Kalyani, Kalyani 741235, WB, India
E-mail: kcm_ku@yahoo.co.in
Received 23 November 2009
The starting material 3 for this study was prepared from 6-
Abstract: A new efficient and simple route for the synthesis of 8,9-
dihydro-3H-pyrano[3,2-f]quinoline-3,10(7H)-dione derivatives has
been accomplished via sulfuric acid promoted condensation–
cyclization of 6-amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-
one and aromatic aldehydes. The products can be oxidized to the
corresponding 10-methoxy-8-aryl-3H-pyrano[3,2-f]quinolin-3-one
derivatives by FeCl3·6H2O in methanol.
amino-5-bromo coumarin (2), which in turn was prepared
from 6-aminocoumarin (1) by bromination with NBS in
MeCN (Scheme 1).15
TMS
Key words: condensation–cyclization, 8,9-dihydro-3H-pyrano[3,2-f]-
quinoline-3,10(7H)-dione, iron(III) chloride, 10-methoxy-8-phenyl-
3H-pyrano[3,2-f]quinolin-3-one
Br
NH2
NH2
NH2
(i)
O
(ii)
O
O
O
O
O
1
2
3
The importance of quinoline and its annulated derivatives
are well known.1 2-Aryl-2,3-dihydroquinoline-4-(1H)-
ones are valuable precursors for the synthesis of medici-
nally important compounds.2 Compounds containing
quinoline moiety have wide application in medicinal3
chemistry. They possess a broad spectrum of biological
activities like antimalarial, anti-inflammatory, antiasth-
matic, antihypertensive, antibacterial, anticancer, and
tyrosine kinase inhibiting agents.4 4-Alkoxy-2-aryl quin-
oline derivatives show bioactivities5 like antiplatelet.6 Al-
kaloids containing the pyranoquinoline core constitute a
significant group of the quinoline alkaloids, and these
compounds have been shown to exhibit a range of biolog-
ical activities.7 Some examples of natural products con-
taining the pyranoquinoline core structure include
helietidine, dutadrupine, and geibalansine.8
Scheme 1 Reagents and conditions: (i) NBS, anhyd MeCN, r.t., 30
min; (ii) (trimethylsilyl)acetylene, Pd(PPh3)Cl2 (5 mol%), CuI (5
mol%), DMF–THF–Et3N (5:3:2), 70 °C, sealed tube, 8 h.
To examine the condensation leading to cyclization of 6-
amino-5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one (3)
with aromatic aldehydes 4 we first attempted the reaction
with benzaldehyde (4a) as a precursor. When substrate 3
(1 equiv) and benzaldehyde (4a, 1 equiv) were refluxed in
methanol in the presence of H2SO4 (1 equiv) for 2.5 hours
product 5a was obtained in 77% yield16 (Scheme 2).
TMS
O
CHO
NH2
NH
(i)
Literature survey reveals several reports on the synthesis
of 2-aryl-2,3-dihydroquinoline-4(1H)-ones9 and 4-
alkoxy-2-aryl quinoline derivatives,10 and most of them
are of limited synthetic scope due to low yields, long
reaction time,10g multiple steps,11 need large amount of
catalyst, specialized solvents,12 toxic reagents,10,13 and mi-
crowave irradiation.9d,e Furthermore, there are no reports
on the synthesis of pyranone-annulated quinoline deriva-
tives. In continuation of our work on the synthesis of quin-
oline-annulated heterocyclic compounds,14 we became
interested in the synthesis of 8,9-dihydro-3H-pyrano[3,2-
f]quinoline-3,10(7H)-dione and 10-methoxy-8-aryl-3H-
pyrano[3,2-f]quinolin-3-one derivatives. Herein, we re-
port our results.
+
O
O
O
O
3
4a
5a
Scheme 2 Reagents and conditions: (i) H2SO4 (1.0 equiv), MeOH,
reflux, 2.5 h.
The optimized conditions for the condensation–cycliza-
tion were achieved through a series of experiments, in
which sequential changes were made in case of the acid
and also its concentration and solvent used for the reaction
(Table 1).
When the reaction of 3 (1 equiv) and 4a (1 equiv) in the
presence of H2SO4 (1 equiv) is carried out in refluxing
methanol, 62% yield of the product was obtained after 2
hours (entry 1) and maximum yield was obtained after 2.5
hours (entry 2). Further increase of time did not improve
the yield of the product (entry 3). When the amount of
SYNLETT 2010, No. 5, pp 0735–0740
1
6.
3
.2
0
1
0
Advanced online publication: 08.02.2010
DOI: 10.1055/s-0029-1219378; Art ID: G36309ST
© Georg Thieme Verlag Stuttgart · New York

736
K. C. Majumdar et al.
LETTER
H2SO4 was varied from 0.5–1.5 equivalents (entries 2–5),
maximum yield of product was obtained when 1.0 equiv-
alent of H2SO4 was used. Among various acids used
(H2SO4, HCl and BF3·OEt2), H2SO4 was found to be supe-
rior to others (entries 2, 6, and 7) when 1.0 equivalent of
each was employed in refluxing methanol. Variation of
solvents did not show any remarkable effect on the yield
of the product (entries 8 and 9). Similar is the case when
2 or more equivalents of benzaldehyde were used instead
of 1 equivalent. Among various conditions employed the
reaction of 3 (1 equiv), benzaldehyde (4a, 1 equiv) and
concentrated H2SO4 (1 equiv) in refluxing methanol was
found to give the best result.
Table 1 Effect of Acids and Solvents on Condensation–Cyclization
of 3 with Benzaldehyde (4a)
Entry Acid (equiv)
Solvent
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
concd H2SO4 (1.00)
2.0
2.5
4.0
2.5
2.5
2.5
2.5
2.5
2.5
62
77
76
58
74
42
49
77
76
concd H2SO4 (1.00)
concd H2SO4 (1.00)
concd H2SO4 (0.50)
concd H2SO4 (1.50)
concd HCl (1.00)
BF3·OEt (1.00)
The substrate 3 was treated with other aromatic aldehydes
4b–k under the optimized conditions to give cyclized
products 5b–l in 18–75% yields (Table 2).
concd H2SO4 (1.00)
concd H2SO4 (1.00)
i-PrOH
Table 2 Condensation–Cyclization of 3 and 4a–k in Methanol
R
R
O
NH
NH2
H2SO4 (1.0 equiv)
+
ArCHO
MeOH, reflux
4a–k
O
O
O
O
5a–l
3
Entry
R
Aromatic aldehyde 4
Product 5a
Yield (%)b
CHO
O
1
2
3
4
TMS
TMS
TMS
TMS
77
NH
NH
NH
NH
4a
O
O
O
O
O
5a
OMe
OEt
Cl
CHO
O
O
O
73
72
75
OMe
O
4b
5b
CHO
OEt
O
4c
5c
CHO
Cl
O
4d
5d
Synlett 2010, No. 5, 735–740 © Thieme Stuttgart · New York

LETTER
Synthesis of Pyrano[3,2-f]quinolin-3,10-dione Derivatives
737
Table 2 Condensation–Cyclization of 3 and 4a–k in Methanol (continued)
R
R
O
NH
NH2
H2SO4 (1.0 equiv)
+
ArCHO
MeOH, reflux
4a–k
O
O
O
O
5a–l
3
Entry
R
Aromatic aldehyde 4
Product 5a
Yield (%)b
CHO
O
Cl
Br
5
TMS
69
NH
Cl
O
O
4e
5e
CHO
O
6
7
8
TMS
TMS
TMS
70
65
70
NH
Br
O
O
4f
5f
O
O
NH
OHC
O
4g
O
O
5g
CHO
O
NH
O
O
4h
5h
O
O
CHO
O
9
10
11
TMS
TMS
TMS
58
20
18
NH
O
O
O
O
4i
5i
MeO
CHO
OMe
O
NH
4j
O
O
5j
MeO
OMe
CHO
OMe
O
NH
OMe
O
O
4k
5k
Synlett 2010, No. 5, 735–740 © Thieme Stuttgart · New York

738
K. C. Majumdar et al.
LETTER
Table 2 Condensation–Cyclization of 3 and 4a–k in Methanol (continued)
R
R
O
NH
NH2
H2SO4 (1.0 equiv)
+
ArCHO
MeOH, reflux
4a–k
O
O
O
O
5a–l
3
Entry
R
Aromatic aldehyde 4
Product 5a
Yield (%)b
OMe
CHO
Ph
O
12c
Ph
47d
NH
OMe
O
O
4b
5l
a All the reactions were carried out in refluxing MeOH for 2.5 h.
b Isolated yields.
c Reaction is carried out in refluxing MeOH for 6 h.
d Combined yield with other inseparable products.
Reaction of 3 with 1 equivalent of 4b and 1 equivalent of (under acidic conditions) that may be followed by a se-
concentrated H2SO4 in refluxing methanol gave product quence of Mannich reaction with the iminium ion to give
5b in 73% yield (entry 2). When the same reaction was products 5a–k (pathway a).
carried out with 4c and 4d, the desired products 5c and 5d
were obtained in 72% and 75% yields, respectively (en-
tries 3 and 4). A 69% yield of the product 5e was obtained
Alternatively, the initial step may be the formation of im-
inium ions 8 by the condensation of amine 3 and aromatic
aldehydes 4 in the presence of acid, which may then un-
when the reaction was carried out with 4e (entry 5). Sim-
dergo cyclization to form the vinyl cations 9. The vinyl
ilarly, treatment of 4f with 3 under the same reaction con-
cations 9 may react with water and subsequent removal of
ditions afforded the product 5f in 70% yield (entry 6).
a proton may give the enols 10. The intermediate enol
Reaction with heteroaromatic aldehyde like 4g gave the
forms 10 may readily get converted into the products 12,
desired product 5g in 65% yield (entry 7). Using the same
the more stable tautomer. Removal of MeOTMS (when
R = TMS) from 12 may give the final products 5. Com-
pounds 11 were not obtained perhaps due to tautomaric
conversion into 12 is much faster than the aerial oxidation
conditions, reaction of 3 separately with 4h and 4i gave
the desired product in 70% and 58% yields, respectively
(entries 8 and 9). When ortho-substituted aromatic alde-
hydes were used the yields of the products were drastical-
ly reduced (entries 10 and 11). This is perhaps due to the
steric effect. The presence of a bulky group at ortho posi-
tion may prevent cyclization towards the product forma-
tion. Desired product was not obtained when strong
(aromatization) of 10 (pathway b).
We have achieved the synthesis of 8,9-dihydro-3H-pyra-
no[3,2-f]quinoline-3,10(7H)-dione derivatives using sul-
furic acid promoted condensation–cyclization of 6-amino-
5-[(trimethylsilyl)ethynyl]-2H-chromen-2-one and benz-
electron-deficient 3- and 4-nitrobenzaldehydes were used
aldehydes. Our result is interesting in view of the fact that
as aromatic aldehydes. Similarly, the reaction of aliphatic
Zhu et al. reported that they have obtained alkoxy-2-aryl
aldehydes also did not afford the desired cyclized prod-
quinolines10g using sulfuric acid promoted condensation–
cyclization of 2-[2-(trimethylsilyl)ethynyl] anilines with
aryl aldehydes in alcoholic solvents. In the present in-
ucts. When the reaction was attempted by replacing the
TMS group in substrate 3 with a phenyl group using this
protocol, a complex mixture of products was obtained in
stance, addition of water instead of a molecule of alcohol
only 47% yield after 6 hours (entry 12) from which one of
to vinyl cation 8 occurs.
the diastereomers (with coupling constant J = 12 Hz of the
The expected products,10g 10-methoxy-8-phenyl-3H-pyr-
ano[3,2-f]quinolin-3-one derivatives, were not obtained.
Thus, we attempted to transform the products 5 into their
corresponding aromatic derivatives. For this purpose
product 5a was oxidized with FeCl3·6H2O (2.5 equiv) in
methanol for 4 hours and expectedly the aromatized prod-
uct 10-methoxy-8-phenyl-3H-pyrano[3,2-f]quinolin-3-
one 6a was obtained in almost quantitative yield. The
structure of the product was determined from its spectro-
protons attached to the chiral centers) could be isolated by
repeated column chromatography. We also could not de-
termine the relative ratio of the diastereomers in the mix-
ture due to the complex nature of the 1H NMR.
Two different pathways (pathway a and pathway b) may
be considered for the formation of the products 5a–l from
substrates 3 (Scheme 3).
The acid-catalyzed hydration of the TMS alkynes 3 sup-
ported by the b-silylation effect may lead to enols 7a–k
Synlett 2010, No. 5, 735–740 © Thieme Stuttgart · New York

LETTER
Synthesis of Pyrano[3,2-f]quinolin-3,10-dione Derivatives
739
Ar
H
O
O
CH2
NH
+
O
7
R
R
2
+
O
Ar
O
Ar
NH2
+
NH
NH
H2SO4 (1.0 equiv)
MeOH
ArCHO
O
O
– MeOTMS
when R = TMS
MeOH, reflux
2.5 h
O
O
O
O
3
4
12
5 R = TMS
H+
path b
R
R
R
R
Ar
HO
Ar
HO
Ar
Ar
+
H
N
N
NH
[O]
NH
+
H2O
– H+
X
X
O
O
O
O
O
O
O
11
10
8
9
Scheme 3 Probable mechanism for condensation–cyclization reaction
scopic data.17 Compound 5e under the same conditions Acknowledgment
also afforded the product 6e in 95% yield (Scheme 4).
We thank CSIR (New Delhi) and DST (New Delhi) for financial
assistance. Two of us (A.T. and S.P.) are grateful to CSIR (New
Delhi) for their Research Fellowships.
Similarly, other 8,9-dihydro-3H-pyrano[3,2-f]quinoline-
3,10(7H)-dione derivatives should also give the corre-
sponding 10-methoxy-8-aryl-3H-pyrano[3,2-f]quinolin-
3-one derivatives.
References and Notes
(1) (a) Elderfield, R. C. In Heterocyclic Compounds, Vol. 4;
Elderfield, R. C., Ed.; John Wiley: New York/London, 1960,
Chap. 1, 1. (b) Kournetsov, V. V.; Mendez, L. Y. V.;
Gomez, C. M. M. Curr. Org. Chem. 2005, 9, 141.
(c) Bringmann, G.; Reichert, Y.; Kane, V. Tetrahedron
2004, 60, 3539. (d) Sahu, N. S.; Pal, C.; Mandal, N. B.;
Banerjee, S.; Raha, M.; Kundu, A. P.; Basu, A.; Ghosh, M.;
Roy, K.; Bandopadhyay, S. Bioorg. Med. Chem. 2002, 10,
1687. (e) Wright, C. W.; Addac-Kyereme, J.; Breen, A. G.;
Brown, J. E.; Cox, M. F.; Croft, S. L.; Gokeck, Y.; Kendrick,
H.; Phillips, R. M.; Pollet, P. L. J. Med. Chem. 2001, 44,
3187.
O
MeO
R
R
NH
N
(i)
O
O
O
O
5a R = H
5e R = Cl
6a R = H (99%)
6e R = Cl (95%)
Scheme 4 Reagents and conditions: (i) FeCl3·6H2O, MeOH, reflux
for 4 h.
(2) (a) Prakash, O.; Kumar, D.; Saini, R. K.; Singh, S. P. Synth.
Commun. 1994, 24, 2167. (b) Singh, O. V.; Kapil, R. S.
Synth. Commun. 1993, 23, 277. (c) Kalinin, V. N.;
Shostakovsky, M. V.; Ponomaryov, A. B. Tetrahedron Lett.
1992, 33, 373. (d) Xia, Y.; Yang, Z.-Y.; Xia, P.; Bastow,
K. F.; Tachibana, Y.; Kuo, S.-C.; Hamel, E.; Hackl, T.; Lee,
K.-H. J. Med. Chem. 1998, 41, 1155.
(3) Antimalarial Drugs II; Peters, W.; Richards, W. H. G., Eds.;
Springer: Berlin, 1984.
(4) (a) Maguire, M. P.; Sheets, K. R.; McVety, K.; Spada, A. P.;
Zilberstein, A. J. Med. Chem. 1994, 37, 2129.
In conclusion, we have demonstrated an efficient strategy
for the unusual formation of 8-aryl-8,9-dihydro-3H-pyra-
no[3,2-f]quinoline-3,10(7H)-dione derivatives by con-
densative
cyclization
of
6-amino-5-[(trimethyl-
silyl)ethynyl]-2H-chromen-2-one with aromatic alde-
hydes in alcoholic solvents promoted by sulfuric acid. The
methodology is simple, rapid, and inexpensive affording
moderate to good yields of products 5a–l which can be
further converted into other derivatives.
(b) Kalluraya, B.; Sreenivasa, S. Farmaco 1998, 53, 399.
(c) Dube, D.; Blouin, M.; Brideau, C.; Chan, C.-C.;
Desmarais, S.; Ethier, D.; Falgueyret, J.-P.; Friesen, R. W.;
Girard, M.; Girard, Y.; Guay, J.; Riendeau, D.; Tagari, P.;
Young, R. N. Bioorg. Med. Chem. Lett. 1998, 8, 1255.
(d) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli, F.; Ghia,
H. Eur. J. Med. Chem. 2000, 35, 1021. (e) Benkovic, S. J.;
Baker, S. J.; Alley, M. R. K.; Woo, Y.-H.; Zhang, Y.-K.;
Akama, T.; Mao, W.; Baboval, J.; Rajagopalan, P. T. R.;
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Synlett 2010, No. 5, 735–740 © Thieme Stuttgart · New York

740
K. C. Majumdar et al.
LETTER
Wall, M.; Kahng, L. S.; Tavassoli, A.; Shapiro, L. J. Med.
Chem. 2005, 48, 7468. (f) Vargas, L. Y.; Castelli, M. V.;
Kouznetsov, V. V.; Urbina, J. M.; Lopez, S. N.; Sortino, M.;
Enriz, R. D.; Ribas, J. C.; Zacchino, S. Bioorg. Med. Chem.
2003, 11, 1531. (g) Dassonneville, L.; Bonjean, K.; De
Pauw-Gillet, M.-C.; Colson, P.; Houssier, C.; Quetin-
Leclercq, J.; Angenot, L.; Ablordeppey, S. Y. Bioorg. Med.
Chem. 2002, 10, 1337.
(14) (a) Majumdar, K. C.; Taher, A.; Debnath, P. Synthesis 2009,
793. (b) Majumdar, K. C.; Chattopadhyay, B.; Taher, A.
Synthesis 2007, 3647. (c) Majumdar, K. C.; Debnath, P.;
Taher, A. Lett. Org. Chem. 2008, 5, 169.
(15) Majumdar, K. C.; Mondal, S. Tetrahedron Lett. 2008, 49,
2418.
(16) General Procedure for the Preparation of Compound 5a
A mixture of 6-amino-5-[(trimethylsilyl)ethynyl]-2H-
chromen-2-one (3, 50 mg, 0.194 mmol), benzaldehyde (4a,
21 mg, 0.194 mmol) and concd H2SO4 (19 mg, 0.194 mmol)
was refluxed in MeOH for 2.5 h. After completion of the
reaction as monitored by TLC, the reaction mixture was
cooled, and the solvent was removed under vacuum and
diluted with H2O (50 mL). The mixture was extracted with
EtOAc (3 × 25 mL). The combined organic extract was
washed with a sat. solution of NaHCO3, followed by brine
solution, and dried over anhyd Na2SO4. The solvent was
distilled off. The crude product was purified by column
chromatography over silica gel (60–120 mesh) using PE–
EtOAc (75:25) mixture as eluent to give 8-phenyl-8,9-
dihydro-3H-pyrano[3,2-f]quinoline-3,10 (7H)-dione (5a);
yield 77%, orange color solid; mp 160–162 °C. IR (KBr):
(5) (a) Goodwin, S.; Smith, A. F.; Valsquez, A. A.; Horning,
E. C. J. Am. Chem. Soc. 1959, 81, 6209. (b) Fournet, A.;
Vagneur, B.; Rilchomme, P.; Bruneton, J. Can. J. Chem.
1989, 67, 2116.
(6) Ko, T.-C.; Hour, M.-J.; Lien, J.-C.; Teng, C.-M.; Lee, K.-H.;
Kuo, S.-C.; Huang, L.-J. Bioorg. Med. Chem. Lett. 2001, 11,
279.
(7) (a) Michael, J. P. Nat. Prod. Rep. 2000, 17, 603.
(b) Michael, J. P. Nat. Prod. Rep. 2004, 21, 650.
(8) (a) Marco, J. L.; Carreiras, M. C. J. Med. Chem. 2003, 6,
518. (b) Puricelli, L.; Innocenti, G.; Delle Monache, G.;
Caniato, R.; Filippini, R.; Cappelletti, E. M. Nat. Prod. Lett.
2002, 16, 95. (c) Corral, R. A.; Orazi, O. O. Tetrahedron
Lett. 1967, 7, 583. (d) Sekar, M.; Rejendra Prasad, K. J.
J. Nat. Prod. 1998, 61, 294.
n
max = 1299, 1656, 1713, 3318 cm–1. 1H NMR (400 MHz,
(9) (a) Donnelly, J. A.; Farrell, D. F. Tetrahedron 1990, 46,
885. (b) Donnelly, J. A.; Farrell, D. F. J. Org. Chem. 1990,
55, 1757. (c) Tokes, A. L.; Litkei, G. Synth. Commun. 1993,
23, 895. (d) Varma, R. S.; Sani, R. K. Synlett 1997, 857.
(e) Kumar, K. H.; Muralidharan, D.; Perumal, P. T. Synthesis
2004, 63. (f) Ahmed, N.; van Lier, J. E. Tetrahedron Lett.
2006, 47, 2725. (g) Ahmed, N.; van Lier, J. E. Tetrahedron
Lett. 2007, 48, 13. (h) Kumar, K. H.; Perumal, P. T. Can. J.
Chem. 2006, 84, 1079. (i) Chandrasekhar, S.; Vijeender, K.;
Sridhar, C. Tetrahedron Lett. 2007, 48, 4935. (j) Kumar,
D.; Patel, G.; Kumar, A.; Roy, R. K. J. Heterocycl. Chem.
2009, 46, 791.
(10) (a) Singh, O. V.; Kapil, R. S. Synlett 1992, 751. (b) Verma,
R. S.; Kumar, D. Tetrahedron Lett. 1998, 39, 9113.
(c) Mphahlele, M. J.; Mogamisi, F. K.; Tsanwani, M.;
Hlatshwayo, M. S.; Mampa, M. R. J. Chem. Res., Synop.
1999, 706. (d) Arcadi, A.; Marinelli, F.; Rossi, E.
Tetrahedron 1999, 55, 13233. (e) Kumar, K. H.; Perumal,
P. T. Tetrahedron 2007, 63, 9531. (f) Kumar, K. H.;
Muralidharan, D.; Perumal, P. T. Tetrahedron Lett. 2004,
45, 7903. (g) Wang, Y.; Peng, C.; Liu, L.; Zhao, J.; Su, L.;
Zhu, Q. Tetrahedron Lett. 2009, 50, 2261.
CDCl3): d = 2.72–2.78 (m, 1 H), 2.87 (dd, J = 14.0, 16.0 Hz,
1 H), 4.69 (s, 1 H), 4.71 (dd, J = 4.0, 14.0 Hz, 1 H), 6.41 (d,
J = 10.0 Hz, 1 H), 6.83 (d, J = 9.2 Hz, 1 H), 7.25 (d, J = 9.2
Hz, 1 H), 7.28–7.40 (m, 5 H), 9.28 (d, J = 10.0 Hz, 1 H) ppm.
13C NMR (100 MHz): d = 47.1, 58.0, 110.7, 117.8, 118.2,
120.9, 124.4, 126.5, 128.7, 129.1, 140.0, 142.1, 148.0,
150.1, 160.3, 194.3 ppm. MS: m/z = 292.1 [M + H]+. Anal.
Calcd (%) for C18H13NO3: C, 74.22; H, 4.50; N, 4.81. Found:
C, 74.49; H, 4.43; N, 4.70.
(17) General Procedure for the Preparation of Compound 6a
A solution of 8-phenyl-8,9-dihydro-3H-pyrano[3,2-f]-
quinoline-3,10 (7H)-dione (5a, 50 mg, 0.172 mmol) in
MeOH (15 mL), FeCl3·6H2O (116 mg, 0.430 mmol) was
added, and the mixture was refluxed on a water bath for 4 h.
After completion of the reaction as monitored by TLC, the
reaction mixture was cooled and diluted with H2O (50 mL).
This was extracted with EtOAc (3 × 25 mL). The combined
organic extract was washed with brine solution and dried
over anhyd Na2SO4. The solvent was distilled off. The
resulting crude product was purified by column chromatog-
raphy over silica gel (60–120 mesh) using PE–EtOAc
mixture (1:1) as eluent to give 10-methoxy-8-phenyl-3H-
pyrano[3,2-f]quinolin-3-one (6a); yield 99%; pale yellow
solid; mp 224–226 °C. IR (KBr): nmax = 1297, 1563, 1704,
3356 cm–1. 1H NMR (400 MHz, CDCl3): d = 4.22 (s, 3 H),
6.52 (d, J = 10.0 Hz, 1 H), 7.40 (s, 1 H), 7.47–7.57 (m, 3 H),
7.67 (d, J = 9.2 Hz, 1 H), 8.12–8.15 (m, 2 H), 8.26 (d, J = 9.6
Hz, 1 H), 9.31 (d, J = 10.0 Hz, 1 H) ppm. 13C NMR (100
MHz, CDCl3): d = 55.9, 100.7, 113.1, 115.2, 115.4, 121.0,
127.3, 128.9, 129.7, 134.7, 139.0, 143.8, 147.5, 153.9,
158.1, 160.3, 164.3 ppm. HRMS: m/z calcd for C19H13NO3
[M + H]+: 304.0968; found: 304.0938.
(11) (a) Goodwin, S.; Smith, A. F.; Horning, E. C. J. Am. Chem.
Soc. 1957, 79, 2239. (b) Elderfield, E. C.; White, J. B. J. Am.
Chem. Soc. 1946, 68, 1276.
(12) (a) Tokes, A. L.; Szilagyi, L. Synth. Commun. 1987, 17,
1235. (b) Tokes, A. L.; Litkei, G.; Szilagyi, L. Synth.
Commun. 1992, 22, 2433.
(13) (a) Singh, O. V.; Kapil, R. S. Synlett 1992, 751. (b) Varma,
R. S.; Kumar, D. Tetrahedron Lett. 1998, 39, 9113.
Synlett 2010, No. 5, 735–740 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.