A simple and expedient synthesis of functionalized pyrido[2,3-c] coumarin derivatives using molecular iodine catalyzed three-component reaction

Article abstract of DOI:10.1016/j.tetlet.2012.09.051

A wide variety of substituted pyrido[2,3-c] coumarin derivatives have been accomplished from 3-aminocoumarins, aromatic aldehydes, and alkynes in the presence of 10 mol % molecular iodine in acetonitrile under reflux conditions through one-pot Povarov reactions. Good yields, no need of aqueous work-up procedure and chromatographic separation, environmentally benign are some of the salient features of the present protocol.

Full text of DOI:10.1016/j.tetlet.2012.09.051

Tetrahedron Letters 53 (2012) 6418–6422
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A simple and expedient synthesis of functionalized pyrido[2,3-c] coumarin
derivatives using molecular iodine catalyzed three-component reaction
⇑
Abu T. Khan , Deb K. Das, Kobirul Islam, Pradipta Das
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 July 2012
Revised 10 September 2012
Accepted 13 September 2012
Available online 21 September 2012
A wide variety of substituted pyrido[2,3-c] coumarin derivatives have been accomplished from 3-amino-
coumarins, aromatic aldehydes, and alkynes in the presence of 10 mol % molecular iodine in acetonitrile
under reflux conditions through one-pot Povarov reactions. Good yields, no need of aqueous work-up
procedure and chromatographic separation, environmentally benign are some of the salient features of
the present protocol.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reaction
Povarov reactions
3-Aminocoumarins
Aromatic aldehydes
Phenylacetylenes
Pyrido[2,3-c] coumarin derivatives
Molecular iodine
Coumarins are a well-known important class of naturally occur-
ring compounds1 and they exhibit a wide range of pharmacological
activities such as antifungal, antibacterial, antitumor, anti-HIV,
antioxidant, and anti-inflammatory activities.2 Among the various
coumarin derivatives, 3-aminocoumarin structural moiety is pres-
ent in many naturally occurring alkaloids such as ningalin B,3a
lamellarin D,3b and santigonamin,3c which display many biological
activities (Fig. 1). Interestingly, the same skeleton is also present in
an antibiotic novobiocin,4 which is produced by the actinomycete
Streptomyces niveus.4 It acts as a potent competitive inhibitor of
the ATPase reaction catalyzed by GyrB. Moreover, pyridocoumarin
derivatives are well known as CNS depressant,5a with antitumor,5b
anti-inflammatory,5c and antimicrobial activities.5d Furthermore,
they also exhibit interesting photochemical properties and have
been used as laser dyestuffs,6a–c luminescence intensifiers,7 and
spasmolytics.8
These compounds are also considered as ‘privileged structures’
in the medicinal chemistry due to their immense potentiality.9 Due
to their wide range of biological activities, various research groups
have put forward considerable efforts to synthesize these com-
pounds in recent times.
From the literature it is found that only a few methods are
known so far for the synthesis of pyrido[2,3-c] coumarin deriva-
tives. The first synthesis of pyrido[2,3-c] coumarin was reported
by Gremal and his co-worker10a from 3-aminocoumarin in moder-
ate yield through Skraup reaction. A few years ago, Guillaumet
et al. demonstrated the synthesis of these derivatives from 3-
hydroxycoumarin in a three step sequence followed by dehydroge-
nation with DDQ.10b Later on, Majumdar et al. devised a new syn-
thetic protocol for the synthesis of pyrido[2,3-c] coumarins10c
through the palladium catalyzed intramolecular Heck reaction fol-
lowed by dehydrogenation with 10% palladium charcoal. Later on,
Bodwell and his co-workers reported the synthesis of pyrido[2,3-c]
coumarin derivatives using Yb(OTf)3 catalyst through the intermo-
lecular Povarov reaction followed by oxidation with molecular
bromine or nitrous gases.10d Very recently, the same group also
reported the synthesis of pyrido[2,3-c] coumarins10c involving
the intramolecular Povarov reaction from 3-aminocoumarin and
2-(propargyloxy)benzaldehyde in 45% yield after 9 days.10e The
main demerits of the above protocols are low yield,10a requirement
of expensive metal catalysts,10c–e and prolonged reaction time.10e
Consequently, there is further scope to develop a synthetic meth-
odology using a less expensive and environmentally benign cata-
lyst. Very recently, we have reported the synthesis of fused
heterocycles containing 3-aminocoumarin skeleton through multi-
component reactions (MCRs).11 Therefore, we perceived 3-amino-
coumarin could be exploited for the synthesis of pyrido[2,3-c]
coumarin derivatives through multicomponent reactions.12 Re-
cently, we have also reported the synthesis of tetrahydroquinoline
derivatives through the one-pot multicomponent reaction involv-
ing the Povarov reaction.13 Therefore, we intended to explore the
Povarov reaction for the synthesis of pyrido[2,3-c] coumarin
derivatives from 3-aminocoumarins, aromatic aldehydes, and
⇑
Corresponding author. Tel.: +91 361 2582305; fax: +91 361 2582349.
E-mail address: atk@iitg.ernet.in (A.T. Khan).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.09.051

A. T. Khan et al. / Tetrahedron Letters 53 (2012) 6418–6422
6419
O
O
OH
O
OH
HO
HO
OH
N
N
O
HO
HO
O
OH
O
HO
O
Ningalin B
Lamellarin D
OH
Me2N
OH
H
N
N
O
O
O
O
O
O
OMe
Santiagonamine
O
O
MeO
Novobiocin 1
O
H2N
Figure 1. Some of naturally occurring potent alkaloids and antibiotic containing 3-aminocoumarin structural unit.
R2
Ar
I2 (10 mol%)
MeCN
R1
NH2
O
CHO
R1
N
O
R2
Ar
1-3 hr
O
O
4
3
2
1
R1 = H/ Br/ OMe
R2 = H/Cl/Br/F/Me/MeO/CN/NO2
Ar = C6H5-/4-CH3C6H4-/4-tert-Bu-C6H4-/3,4-(CH3)2C6H3-/3,5-(CH3)2C6H3-/1-C10H7-
Scheme 1. One-pot synthesis of pyrido[2,3-c] coumarin derivatives.
phenylacetylenes. It is well established in the literature that the
Table 1
combination of aryl amines, aromatic aldehydes, and alkynes
has been exploited for the synthesis of various quinoline deriva-
tives through MCRs using molecular iodine in nitromethane14a or
using expensive metal catalysts.14b–f Likewise, the synthesis of
imidazo[1,2-a]pyridines was accomplished from 2-aminopyridine,
aromatic aldehydes, and acetylenes.15 Likewise, Majumdar et al.
demonstrated of the synthesis of pyrano[3,2-g] quinoline deriva-
tives using either 6-aminocoumarin or 6-amino quinolone through
the Povarov reaction using BF3.OEt2.16 In recent times, it is found
that molecular iodine is a useful catalyst for MCRs since it is less
expensive, non-toxic, easily available, and environmentally accept-
able, which has been used for MCRs by us17 as well as by others.18
The importance and usefulness of molecular iodine in various
organic transformations have been reviewed recently.19 In this Let-
ter, we wish to report the simplest, rapid, and one-pot synthesis of
pyrido[2,3-c] coumarin derivatives involving molecular iodine via
the imino-Diels–Alder reaction using 3-aminocoumarins, aromatic
aldehydes, and phenylacetylenes as shown in Scheme 1.
Optimization of reaction conditions for the synthesis of pyrido[2,3-c] coumarin
derivative (4b)a
Entry
Catalyst
Mol % of
catalyst
Solvent
Reaction
condition
Time
(h)
Yieldb
(%)
1
2
3
4
5
6
7
8
Iodine
Iodine
Iodine
Iodine
Iodine
Iodine
Iodine
Iodine
CAN
TfOH
InCl3
AgOTf
No catalyst
5
CH3CN
CH3CN
CH3CN
CH3NO2
Toluene
DCE
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
rt
Reflux
Reflux
Reflux
Reflux
Reflux
3.5
2.5
2.5
2.5
3.5
3.5
6.0
12.0
12.0
12.0
12.0
12.0
12.0
68
82
78
78
70
56
42
22
26
48
36
00
00
10
20
10
10
10
10
10
10
10
10
10
EtOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
9
10
11
12
13
a
All the reactions were performed with 3-aminocoumarin (1.0 mmol), 4-chlo-
robenzaldehyde (1.0 mmol), and phenylacetylene (1.5 mmol).
b
Isolated yields.
For the present study, the mixture of 4-chlorobenzaldehyde
(1 mmol), 3-aminocoumarin (1 mmol), and phenylacetylene
(1.5 mmol) in 4 mL of acetonitrile was refluxed in the presence of
5 mol % of molecular iodine and the product pyrido[2,3-c] couma-
rin derivative 4b was obtained in 68% yield (Table 1, entry 1).
Product 4b was characterized from 1H NMR, 13C NMR spectra,
and elemental analysis. The same set of reactions were carried
out using 10 mol % and 20 mol % I2 (Table 1, entries 2 and 3)
successively and the desired product 4b was obtained in 82% and
78% yield, respectively. It was observed that the yield of the
product was increased significantly by increasing the amount of
catalyst from 5% to 10%.
For scrutinizing the suitable solvent system, similar reactions
(entries 4–7) were conducted in various solvent systems such as
nitromethane, toluene, dichloroethane (DCE), and ethanol under
reflux conditions, respectively. It was noted that the shortest reac-
tion time and the best yield are obtained in acetonitrile (entry 2)
under reflux conditions. It was also noted that a similar reaction
can be performed with nitromethane in the same yield. However,
all the reactions were carried out in acetonitrile because of its low-
er cost as well as toxicity than those of nitromethane. Interestingly,
the same reaction provided low yield when it was carried out at

6420
A. T. Khan et al. / Tetrahedron Letters 53 (2012) 6418–6422
Table 2
Synthesis of various substituted pyrido[2,3-c] coumarin derivatives using Povarov reactiona
R2
I2 (10 mol%)
MeCN
R1
N
O
R1
NH2
O
CHO
R2
1-3 hr
O
O
1
2
3
4
Entry
R1
R2
H
4-Cl
4-Br
4-F
2-Cl
4-Me
4-OMe
4-NO2
4-CN
4-Cl
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
3
2.5
1
3
3
1
1
0.25
0.5
3
78
82
88
82
72
88
89
94
91
81
78
77
76
78
76
9
H
10
11
12
13
14
15
Br
Br
Br
Br
OMe
OMe
4-Br
3
2
2
2
4-Me
4-MeO
4-Cl
4-Me
2
a
The reactions were carried out with 3-aminocoumarins (1.0 mmol), aromatic aldehydes (1.0 mmol), and phenylacetylene (1.5 mmol) in the presence of 10 mol % of iodine
in 4 mL of CH3CN under reflux conditions.
b
Isolated yields.
Table 3
Synthesis of various substituted pyrido[2,3-c] coumarin derivatives using Povarov reactiona
R2
Ar
I2 (10 mol%)
MeCN
CHO
R1
R1
NH2
O
N
O
R2
Ar
1-3 hr
O
O
4
3
2
1
Entry
R1
R2
Ar
Product
Time
Yieldb (%)
1
2
3
4
5
6
7
H
4-Cl
H
4-CH3C6H4–
4-CH3C6H4–
4-CH3C6H4–
3,4-(CH3)2C6H3–
3,5-(CH3)2C6H3–
4-tert-Bu-C6H4-
1-C10H7–
4p
4q
4r
4s
4t
2
2
2
2
2
2
2.5
75
72
78
76
81
82
78
OMe
OMe
H
H
H
4-F
4-Cl
4-Cl
4-Cl
4-Cl
4u
4v
H
a
The reactions were carried out with 3-aminocoumarins (1.0 mmol), aromatic aldehydes (1.0 mmol), and substituted phenylacetylenes (1.5 mmol) in the presence of
10 mol % of iodine in 4 mL of CH3CN under reflux conditions.
b
Isolated yields.
room temperature (Table 1, entry 8). To examine the efficacy of
molecular iodine as compared to other catalysts, several reactions
were also scrutinized in the presence of catalysts like CAN, AgOTf,
and InCl3, respectively, (Table 1 entries 9–12).
After optimization of the reaction conditions, we performed a
reaction with a mixture of 3-aminocoumarin, benzaldehyde, and
phenylacetylene under identical conditions and the desired prod-
uct 4a was obtained in 78% yield. To explore the synthetic scope
further and the generality of the present protocol,20 various reac-
tions were examined with a wide variety of aromatic aldehydes
containing different substituents in the aromatic ring such as Cl,
Br, F, Me, OMe, and NO2 with 3-aminocoumarin and phenylacety-
lene, respectively. The reaction time and percentage yield of the
products (4b–i) are shown in Table 2 (entries 2–9). It is worthwhile
to mention that the pure products were isolated simply by filtra-
tion, which is purified by recrystallization from dichlorometh-
ane–hexane solvent system. For verifying the generality of the
Figure 2. Single crystal X-ray structure 4o (CCDC 876435).

A. T. Khan et al. / Tetrahedron Letters 53 (2012) 6418–6422
6421
R2
R2
Ar
3
R1
NH2
O
I2
R1
N
O
+
H
I2
CH3CN, reflux
O
O
A
O
1
2
R2
R2
R2
H
Ar
Ar
H
Ar
[O]
air
R1
R1
NH
O
N
O
N
O
R1
O
O
O
4
C
B
Scheme 2. Mechanism for the synthesis of pyrido[2,3-c] coumarin derivatives.
present method, other substituted 3-aminocoumarins such as
6-bromo-3-aminocoumarin and 6-methoxy-3-aminocoumarin
were also tested with aromatic aldehyde and phenyl acetylene
under identical reaction conditions and the desired pyrido[2,3-c]
coumarin derivatives 4j–o were obtained in good yields (Table 2,
entries 10–15).
Furthermore, the same reactions were also executed with dif-
ferent substituted phenylacetylenes with 3-aminocoumarin and
aromatic aldehyde to give products 4p–v (Table 3, entries 1–7).
Unfortunately, we did not get the desired product when aliphatic
aldehyde such as cyclohexaldehyde was treated with 3-amino-
coumarin and phenylacetylene in the presence of I2 under identical
reaction conditions.
thankful to DST for providing XRD facility under the FIST
programme.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.09.
051.
References and notes
1. Murray, D. H.; Mendez, J.; Brown, S. A. The Natural Coumarins: Occurrence,
Chemistry and Biochemistry; J. Wiley & Sons: New York, 1982.
2. (a) O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applications and Mode of
Action; J. Wiley & Sons: Chichester, 1997; (b) Fylaktakidou, K. C.; Hadjipavlou-
Litina, D. J.; Litinas, K. E.; Nicolaides, D. N. Curr. Pharm. Des. 2004, 10, 3813; (c)
Zhang, W.; Pugh, G. Tetrahedron Lett. 2001, 42, 5613.
3. (a) Kang, H.; Fenical, W. J. Org. Chem. 1997, 62, 3254; (b) Andersen, R. J.;
Faulkner, D. J.; He, C.; Van Duyne, G. D.; Clardy, J. J. Am. Chem. Soc. 1985, 107,
5492; (c) Lewis, W. H.; Stonard, R. J.; Porras-Reyes, B.; Mustoe, T. A.; Thomas, A.
U.S. Patent 5,156,847, 1992; Chem. Abstr. 1992, 117, 245630t.
The structure of one of the representative compounds such as
4o was confirmed unambiguously by single crystal X-ray diffrac-
tion analysis (see Supplementary data) (Fig. 2). All the structures
were confirmed from 1H NMR, 13C NMR spectra, and from their
elemental analysis.
The formation of the product may be explained as follows: We
believe that the condensation reaction between 3-aminocoumarin
(1) and aromatic aldehyde (2) leads to the formation of intermedi-
ate imines A, which undergoes the Povarov reaction with dieno-
phile such as alkyne (3) to afford pyrido[2,3-c] coumarin
derivatives 4 through the intermediate dihydropyridine B followed
by aerial oxidation as shown in Scheme 2.
4. Oeksema, H.; Johnson, J. L.; Hinman, J. W. J. Am. Chem. Soc. 1955, 77, 6710.
5. (a) Kulkarni, Y. D.; Srivastava, D.; Bishnoi, A.; Dua, P. R. J. Indian Chem. Soc. 1996,
73, 173; (b) Marcu, M. G.; Schulte, T. W.; Neckers, L. J. Natl. Cancer Inst. 2000, 92,
242; (c) Melagraki, G.; Afantitis, A.; Igglessi-Markopoulou, O.; Detsi, A.;
Koufaki, M.; Kontogiorgis, C.; Hadjipavlou- Litina, D. J. Eur. J. Med. Chem.
2009, 44, 3020; (d) Rodighiero, G.; Antonello, C. Boll. Chim. Farm. 1958, 97, 592.
6. (a) Hammond, P. R.; Atkins, R. L. J. Heterocycl. Chem. 1978, 12, 1061; (b) Atkins,
R. L.; Bliss, D. E. J. Org. Chem. 1978, 43, 1975; (c) Grandberg, I. I.; Denisov, L. K.;
Popova, O. A. Khim. Geterotsikl. Soedin. 1987, 2, 147.
In conclusion, we have demonstrated a more efficient and expe-
dient synthetic protocol for the synthesis of pyrido[2,3-c] coumarin
derivatives by employing environmentally benign catalyst molecu-
lar I2 via one-pot three-component condensation reaction from a
wide variety of 3-aminocoumarins, aromatic aldehydes, and phe-
nylacetylenes without involving any co-oxidant in good yields. In
addition, co-oxidant such as nitromethane can be avoided which
is harmful and expensive in the present protocol. The reaction con-
dition is simple and transformation is quite effective for a wide
range of aldehydes and phenylacetylenes. The products are easily
isolable in good to excellent yields without aqueous work-up and
chromatographic separation, and involvement of metal catalyst.
The biological study of these compounds is still underway and will
be reported in due course.
7. Fujimoto, A.; Sakurai, A.; Iwase, E. Bull. Chem. Soc. Jpn. 1976, 49, 809.
8. Mohanty, N.; Rath, P. C.; Rout, K. K. J. Indian Chem. Soc. 1967, 44, 1001.
9. (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; Dipardo, R. M.; Freidinger, R. M.;
Whitter, G. F.; Lundell, W. L.; Veber, D. F.; Anderson, P. S.; Cheng, R. S. L.; Lotti,
V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield,
J. J. Med. Chem. 1988, 31, 2235; (b) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
Chem. Rev. 2003, 103, 893.
10. (a) Khan, M. A.; Gremal, A. L. J. Heterocycl. Chem. 1977, 14, 1009; (b) Pavé, G.;
Chalard, P.; Viaud-Massuard, M.-C.; Troin, Y.; Guillaumet, G. Synlett 2003, 987;
(c) Majumdar, K. C.; Chattopadhyay, B.; Taher, A. Synthesis 2007, 3647; (d)
Kudale, A. A.; Kendall, J.; Miller, D. O.; Collins, J. L.; Bodwell, G. L. J. Org. Chem.
2008, 73, 8437; (e) Kudale, A. A.; Miller, D. O.; Dawe, L. N.; Bodwell, G. J. Org.
Biomol. Chem. 2011, 9, 7196.
11. Khan, A. T.; Das, D. K. Tetrahedron Lett. 2012, 53, 2345.
12. (a) Zhu, J.; Bienaymé, H. Multicomponent Reactions; Wiley-VCH: Weinheim,
2005; (b) Orru, R. V. A.; Ruijter, E. In Synthesis of Heterocyles via Multicomponent
Reactions; Maes, B. U. W., Ed.; Springer-Verlag: Berlin, 2010; Vols. 1 & 2,.
13. Khan, A. T.; Das, D. K.; Khan, M. M. Tetrahedron Lett. 2011, 52, 4539.
14. (a) Li, X.; Mao, Z.; Wang, Y.; Chen, W.; Lin, X. Tetrahedron 2011, 67, 3858; (b)
Zhang, X.; Liu, B.; Shu, X.; Gao, Y.; Lv, H.; Zhu, J. J. Org. Chem. 2012, 77, 501; (c)
Guchhait, S. K.; Jadeja, K.; Madaan, C. Tetrahedron Lett. 2009, 50, 6861; (d) Xiao,
F.; Chen, Y.; Liu, Y.; Wang, J. Tetrahedron 2008, 64, 2755; (e) Huma, H. Z. S.;
Halder, R.; Kalra, S. S.; Das, J.; Iqbal, J. Tetrahedron Lett. 2002, 43, 6485; (f)
Wang, X.-S.; Zhou, J.; Zhang, M.-M.; Wang, W.; Li, Y-L. Monatsh. Chem. 2012,
143, 935.
Acknowledgments
D.K.D. is thankful to IIT Guwahati and CSIR, New Delhi for his
research fellowship. KI acknowledges UGC for his research fellow-
ship. The authors are grateful to the Director, IIT Guwahati for pro-
viding general facilities to carry out the research work. They are
15. (a) Chernyak, N.; Gevorgyan, V. Angew. Chem., Int. Ed. 2010, 49, 2743; (b) Reddy,
B. V. S.; Reddy, P. S.; Reddy, Y. J.; Yadav, J. S. Tetrahedron Lett. 2011, 52, 5789; (c)

6422
A. T. Khan et al. / Tetrahedron Letters 53 (2012) 6418–6422
Suresh, R.; Muthusubramanian, S.; Senthilkumaran, R.; Manickam, G. J. Org.
Chem. 2012, 77, 1468.
starting materials. Finally it was dried through a vacuum pump and the pure
product pyrido[2,3-c] coumarin derivative was obtained after recrystallization
from dichloromethane and hexane.
Spectrocopic data of the pyrido[2,3-c] coumarin derivatives: 1,3-diphenyl-5H-
chromeno[3,4-b]pyridin-5-one (4a). White powder (272 mg, 78%); [Found: C,
82.56; H, 4.41; N, 4.09. C24H15NO2 (349.1103) requires C, 82.50; H, 4.33; N, 4.01];
16. Majumdar, K. C.; Ponra, S.; Ghosh, D.; Taher, A. Synthesis 2011, 104.
17. (a) Khan, A. T.; Khan, M. M.; Bannuru, K. K. R. Tetrahedron 2010, 66, 7762; (b)
Khan, A. T.; Ghosh, A.; Khan, M. M. Tetrahedron Lett. 2012, 53, 2622.
18. (a) Jin, G.; Zhao, J.; Han, J.; Zhu, S.; Zhang, J. Tetrahedron 2010, 66, 913; (b)
Wang, X.-S.; Zhou, J.; Yin, M.-Y.; Yang, K.; Tu, S-J. J. Comb. Chem. 2010, 12, 266;
(c) Jareb, M.; Vrazic, D.; Zupan, M. Tetrahedron 2010, 67, 1355.
19. Togo, H.; Iida, H. Synlett 2006, 2159.
mp 224–225 °C; Rf (30% ethyl acetate/hexane) 0.37; mmax(KBr) = 3084, 1757,
1606 cmÀ1; dH (400 MHz, CDCl3) 6.86–6.90 (m, 1H), 7.05 (d, J = 8 Hz, 1H), 7.34–
7.38 (m, 2H), 7.42–7.51 (m, 5H), 7.52–7.60 (m, 3H), 7.96 (s, 1H), 8.11(d, J = 7.6 Hz,
2 H); dc (100 MHz, CDCl3) 117.20, 117.82, 123.83, 127.45, 127.60, 127.78, 128.34,
129.02, 129.25, 129.66, 130.30, 130.49, 137.18, 139.32, 139.84, 149.03, 150.98,
157.51, 159.12. HRMS (ESI): [M+H]+, Found: m/z 350.1317. C24H15NO2 requires
350.1103. 15.9-methoxy-1-phenyl-3-(p-tolyl)-5H-chromeno[3,4-b]pyridin-5-one
(4o): White powder. (298 mg, 76%); [Found: C, 79.42; H, 4.92; N, 3.52.
20. General procedure for the synthesis of pyrido[2,3-c] coumarin derivatives: In a
25 mL round bottomed flask was taken
a mixture of 3-aminocoumarin
(1.0 mmol) and aromatic aldehyde (1.0 mmol) in 4 mL of acetonitrile. Then,
phenyl acetylene (1.5 mmol) and 10 mol % of molecular iodine (0.025 g) were
added successively into the above reaction mixture and the reaction flask was
transferred for refluxing into a heated oil-bath. The progress of the reaction
was monitored by checking TLC from time to time. Towards the end of the
reaction a solid precipitate starts appearing slowly, after the stipulated time as
mentioned in Tables 2 and 3. The reaction flask was then removed from the oil-
bath and it was brought to room temperature for complete precipitation. The
solid precipitate was just filtered through a Büchner funnel and it was washed
with 10 mL of cold hexane–ethyl acetate mixture (1:1) to remove un-reacted
C
26H19NO3 (393.1365) requires C, 79.37; H, 4.87; N, 3.56]; mp 219–220 °C; Rf
(10% ethyl acetate/hexane) 0.45;
m
max(KBr) 2986, 1745, 1598 cmÀ1. dH (400 MHz,
CDCl3) 8.13 (d, J = 8.0 Hz, 2H), 7.94 (s, 1H), 7.62–7.52 (m, 3H), 7.47 (d, J = 8.0, 2H),
7.32–7.28 (m, 3H), 6.93 (dd, J = 8.8, 2.8, 1H), 6.60 (d, J = 2.4 Hz, 1H), 3.25 (s, 3H,
OMe), 2.43 (s, 3H, -Me); dc (100 MHz, CDCl3) 159.28, 157.27, 155.23, 148.75,
145.14, 140. 58, 140.07, 139.20, 134.28, 129.72, 129.66, 129.08, 128.60, 127.83,
127.28, 126.97, 118.8, 118.59, 117.40, 109.76, 54.89, 21.49.