Regioselective synthesis of pyrano[3,2-f]quinoline and phenanthroline derivatives using molecular iodine

Article abstract of DOI:10.1016/j.tetlet.2013.07.163

A series of polysubstituted pyrano[3,2-f]quinoline and phenanthroline derivatives have been synthesized by molecular iodine-catalyzed tandem reaction of various propargylic alcohols with or without substituted amines in excellent yields. Moreover, the cyclized side products are also pyrano[3,2-f]quinoline and phenanthroline derivatives.

Full text of DOI:10.1016/j.tetlet.2013.07.163

Tetrahedron Letters 54 (2013) 5586–5590
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Regioselective synthesis of pyrano[3,2-f]quinoline and
phenanthroline derivatives using molecular iodine q
⇑
K. C. Majumdar , Sudipta Ponra, Tapas Ghosh
Department of Chemistry, University of Kalyani, Kalyani 741235, WB, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of polysubstituted pyrano[3,2-f]quinoline and phenanthroline derivatives have been synthesized
by molecular iodine-catalyzed tandem reaction of various propargylic alcohols with or without substi-
tuted amines in excellent yields. Moreover, the cyclized side products are also pyrano[3,2-f]quinoline
and phenanthroline derivatives.
Received 18 May 2013
Revised 26 July 2013
Accepted 31 July 2013
Available online 11 August 2013
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords:
Pyrano[3,2-f]quinoline
Phenanthroline
Molecular iodine
Aniline
Propargylic alcohol
OH
The heterocyclic ring system tetrahydroquinoline represents an
important class of alkaloids and are often found as structural frame-
works in a large number of biologically active natural products and
pharmaceuticals.1 Quinoline nucleus has found broad application in
drug development material science,2 bioorganometallic processes,3
and agrochemicals and effect chemicals such as dyestuffs, corrosion
inhibitors, and medicinal chemistry.1 Substituted quinolines show
numerous biological activities as antagonists of endothelin,4
5HT3,5 and NK-3 receptors6 and also function as inhibitors of gastric
(H+/K+)-ATP-ase7 and dihydroorotate dehydrogenase.8 Moreover,
pyrano[3,2-f] quinoline shows unique biological activities, such as
psychotropic,9 antiallergic,10 anti-inflammatory,11 and estrogenic12
activities and are used as potential pharmaceuticals.13 Helietidine,
dutadrupine, and geibalansine14 are examples of natural products
containing pyranoquinoline core structure. 4,7-Phenanthroline
derivatives and its analogs exhibit a high antibacterial activity
and are used for the treatment of gastrointestinal disease.15–20 Be-
cause of the significance of these scaffolds in drug discovery and
medicinal chemistry, efficient synthesis of pyranoquinoline and
phenanthroline derivatives continues to attract the interest of syn-
thetic chemists. However, most classical methods for the synthesis
of the complex substituted tetrahydroquinolines need expensive
Br
NHR
NHR
NHR
OH
(i)
(ii)
O
X
O
X
O
X
2
3
1
X = O, NMe, NEt
R = H, Me, Et
Reagent and condition: (i) NBS, CH3CN, r.t. stirring (ii) Pd(PPh3)2Cl2, CuI, NEt3, DMF, 90 ºC, 3h
Scheme 1. Preparation of starting materials. Reagent and condition: (i) NBS,
CH3CN, rt stirring (ii) Pd(PPh3)2Cl2, CuI, NEt3, DMF, 90 °C, 3 h.
metals, high temperatures or extended reaction times.21 To over-
come the above limitations, an efficient, and environmentally
friendly method with short reaction time is always welcomed.
Recently, molecular iodine has received considerable attention
as an inexpensive, non-toxic, readily available reagent for the prep-
aration of a variety of five- and six-membered carbocyclic and het-
erocyclic ring systems. Thus, iodine-promoted tandem reactions
continue to be an area of active research in synthetic chemistry
due to efficient, mild, and clean reaction conditions.22 As a part
of our continuing efforts toward the development of new protocols
for the expeditious synthesis of biologically relevant heterocyclic
compounds,23 we undertook a simple molecular iodine-induced
tandem cyclization reaction of propargylic alcohols with amines
for the preparation of potentially bioactive substituted pyrano-
quinoline or phenanthroline derivatives.
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-No Derivative Works License, which per-
mits non-commercial use, distribution, and reproduction in any medium, provided
the original author and source are credited.
The starting materials 3 for this study were prepared easily
according to the reactions outlined in Scheme 1. The process
⇑
Corresponding author. Tel.: +91 33 25828750; fax: +91 33 25828282.
E-mail address: kcm@klyuniv.ac.in (K.C. Majumdar).
0040-4039/$ - see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.163

K. C. Majumdar et al. / Tetrahedron Letters 54 (2013) 5586–5590
5587
involves bromination of compound 1 by NBS followed by the Sono-
gashira coupling of brominated derivative 2 with 2-methyl but-3-
yn-2-ol using 5 mol % Pd(PPh3)2Cl2 and 5 mol % CuI in a mixture of
DMF and NEt3 (7 ml: 3 ml) at 90 °C in 77–91% yield. 2-Methyl
but-3-yn-2-ol has been used widely as a readily available, cheap,
non-volatile, protected form of acetylene which is unmasked via
thermolysis in the presence of a base with the expulsion of ace-
tone. Iodine-catalyzed cyclization of the resulting 3a with aromatic
amine to give 5a in 92% yield along with 6a (6%) as side product.
Initially we have used the reaction of 6-(ethylamino)-5-(3-hy-
droxy-3-methylbut-1-ynyl)-2H-chromen-2-one (3a) and naphtha-
len-1-amine (4a) as a model reaction to optimize the reaction
condition and the results are presented in Table 1.
11–14). To establish the optimum reaction conditions THF, CH3OH,
CH3CN, DCE, and CHCl3 (entries 15–19) were also tested as solvents
under the same reaction condition. Variation of the catalyst and
solvent showed that running the reaction in DCM at rt using
10 mol % I2 provides the best result.
To explore the scope and generality of this simple iodine-in-
duced tandem cyclization reaction of propargylic alcohols with
amines, a range of pyrano[3,2-f]quinoline or phenanthroline deriv-
atives were synthesized from a variety of substrates under the
optimized reaction condition. Different types of substituted prop-
argylic alcohol derivatives (3a–f), and a wide range of amines (aro-
matic and heterocyclic), 1a, 1c, and 4a–l were examined. All of
them gave excellent yields of the desired products under the opti-
mized reaction conditions. Table 2 shows that this protocol can be
applied not only to electron rich but also to electron-deficient aro-
matic amines and heterocyclic amines as electronic nature of the
substituents on the aromatic ring of the aldehydes did not show
any influence on the yield of the products of the reaction, thus
demonstrating the wide scope of this protocol. But the reaction
does not give desired product when a strongly electron withdraw-
ing NO2 group is present at the para position of the aromatic ring of
aniline derivatives (entry 11). In this case exclusively the cyclized
product 6b was obtained, which is the side product in other cases.
However NO2 substitution at the meta position ofthe aromatic ring
of amine derivatives (4j) gives exclusively desired product 5k in
just 60 min, without the formation of any side product 6b (entry
12). But, 1H NMR spectra of the product 5k showed that it is mix-
ture of two products which are inseparable by simple column chro-
matography. The reaction does not give any cyclized product when
prop-2-yn-1-ol or but-3-yn-2-ol was used as propargylic alcohols
instead of 2-methyl but-3-yn-2-ol limiting the scope to some
extent.
Further, to expand the scope of this reaction, we have also car-
ried out the same reaction without any aniline derivatives and
with those propargylic alcohols which contain a free amine group
(3c, 3e, 3f). Surprisingly in the presence of 10 mol % I2 pyranoquin-
oline or phenanthroline derivatives 7a, 7b, and 7c were obtained in
excellent yields, without the formation of any type of side product
6 as depicted in Table 3. But when 3a, 3b, and 3d were treated with
10 mol % I2 in the absence of aniline derivatives, solely the cyclized
derivatives pyranoquinoline or phenanthroline derivatives 6a, 6b,
or 6d were obtained. From the aforesaid examples, it is clear that
propargylic alcohol derivatives 3 contain free amine group give
the pyranoquinoline or phenanthroline derivatives in the presence
or absence of another aniline derivative. In the absence of aniline
The reaction was first carried out in moist dichloromethane
without any catalyst at room temperature for 10 h. The reaction
failed to give any product in the absence of any catalyst (Table 1,
entry 1).
A similar reaction was carried out in the presence of 10 mol % of
AcOH (entry 2) and the reaction was completed in 30 min. to give
7-ethyl-8,8-dimethyl-8,9-dihydro-3H-pyrano[3,2-f]quinoline-
3,10(7H)-dione (6a) in 90% yield. In the presence of 10 mol % BF3-
ÁEt2O at rt in DCM (5 ml) for 30 min. afforded 6a as major product
along
with
7-ethyl-8,8-dimethyl-10-(naphthalen-1-ylimino)-
7,8,9,10-tetrahydro-3H-pyrano[3,2-f]quinolin-3-one (5a) in 10%
yield (entry 3). Various catalysts such as TfOH, FeCl3, AlCl3, CuI,
AgSbF6, and InCl3 were investigated in DCM at rt and all of them
gave 6a as the major products and 5a as minor product (entries
4–9) in 30 min. When we carried out the same reaction in the pres-
ence of 10 mol % I2 5a was obtained as the major product (92%)
along with a small amount of 6a (6%) (entry 10). I2 gives better
yield compared to other Lewis acids. Brönsted acids give only the
cyclized product 6a. Lower loading of the catalyst (5 mol %) gives
lower yield (72%) but higher loading of the catalyst (20, 50 or
100 mol %) had no significant effect on the reaction yield (entries
Table 1
Optimization of reaction conditions
OH
N
O
NH2
NEt
NHEt
NEt
+
+
O
O
O
O
O
O
6a
4a
3a
5a
derivatives another molecule of
component.
3 behaves as the aniline
Entry
Catalyst (mol %)
Solventb
Time
% Yield (5a:6a)a
The structures of the products were determined from their ele-
mental analyses and spectroscopic data. The 1H NMR spectra of the
compound 5a as well as two peaks in 13C NMR spectra at dc = 160.9
and 163.8 ppm show the presence of an ester and an imine group.
This is further supported by the mass spectral data of compound 5a
at 397.1910. The hydrolysis of compound 5a to the corresponding
carbonyl compound 6a by H+ (Scheme 2) showed the presence of
an imine group in the products 5.
Two possible pathways may be considered (Scheme 3) for the
iodine-catalyzed tandem cyclization reaction which is similar to
that outlined by Ye et al.25 Path a: first, in the presence of trace
amounts of H+ (formed by I2 and H2O), the propargylic alcohols 3
easily lose the hydroxy group to afford the intermediate propargyl
carbocations A, aniline then subsequently captures the allene cat-
ion to give intermediate B. Intermediate B loses a proton to form
the intermediate C. I2 coordinates with the carbon–nitrogen double
bond and generates intermediate D. Intramolecular nucleophilic
attack of the nitrogen of the amino group gave the intermediate
E, which on deprotonation and protonation afforded the enamine
1
2
3
4
5
6
7
8
—
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
10 h
0
AcOH (10)
BF3ÁOEt2 (10)
TfOH (10)
FeCl3 (10)
AlCl3 (10)
CuI (10)
AgSbF6 (10)
InCl3 (10)
I2(10)
I2 (5)
I2 (20)
I2 (50)
I2 (100)
I2 (10)
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
90 (0:90)
96 (10:86)
95 (0:95)
97 (16:81)
94 (12:82)
96 (17:79)
87 (22:65)
90 (21:69)
98 (92:6)
76 (72:4)
98 (92:6)
98 (92:6)
98 (92:6)
68 (56:12)
86 (72:14)
63 (52:11)
94 (82:12)
97 (91:6)
9
10
11
12
13
14
15
16
17
18
19
I2 (10)
I2 (10)
I2 (10)
I2 (10)
CH3OH
CH3CN
DCE
CHCl3
a
Isolated yield.
All solvents were moist.
b

5588
K. C. Majumdar et al. / Tetrahedron Letters 54 (2013) 5586–5590
Table 2
Synthesis of various pyranoquinoline and phenanthroline derivatives
OH
R1
N
O
NH2
NHR
+
NR
+
O
NR
I2, moist DCM
rt, stirrring
O
X
O
X
3
X
R1
5
6
4
Entry
Substrate
Amine
Time (min)
Products
% Yield (5:6)a
1
2
3
4
5
6
7
8
X = O,R = Et (3a)24
X = O, R = Et (3a)
X = O, R = Et (3a)
X = O, R = Et (3a)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = Me (3b)
X = O, R = H (3c)
X = O, R = H (3c)
X = NEt, R = Et (3d)
X = NEt, R = Et (3d)
Naphthalen-1-amine (4a)
Naphthalen-2-amine (4b)
2,4-Dimethylaniline (4c)
6-Amino-2H-chromen-2-one (1a)
o-Toluidine (4d)
p-Toluidine (4e)
2-Chloroaniline (4f)
5-Chloro-2-methylaniline (4g)
3-Chloro-2-methylaniline (4h)
2-Bromo-4-methylaniline (4i)
4-Nitroaniline (4j)
30
30
30
30
30
30
30
30
30
30
30
60
30
30
30
30
30
5a24 + 6a24
5b + 6a
5c + 6a
5d + 6a
5e + 6b
5f + 6b
5g + 6b
5h + 6b
5i + 6b
5j + 6b
6b
5k + 6b
5l + 6b
5m + 6c
5n + 6c
5o + 6d
5p + 6d
98 (92:6)
97 (91:6)
97 (89:8)
93 (82:11)
95 (88:7)
96 (90:6)
96 (84:12)
98 (87:11)
97 (86:11)
97 (89:8)
84 (0:84)
98 (84:14)
98 (88:10)
96 (68:28)
93 (64:29)
96 (83:13)
95 (82:13)
9
10
11
12
13
14
15
16
17
3-Nitroaniline (4k)
Naphthalen-1-amine (4a)
4-Methoxyaniline (4l)
4-Chloroaniline (4m)
p-Toluidine (4e)
2,4-Dimethylaniline (4c)
a
Isolated yields.
H+ + I+ + I- + OH-
Table 3
I2 + H2O
Synthesis of pyranoquinoline and phenanthroline derivatives from propargylic
alcohols
OH
NH2
R1
H
.
.
O
N
+
H
+
OH
NHR
R1
4
NHR
OH
H+
Path a
X
NHR
Iδ−
O
X
O
X
B
O
X
N
3
A
I2 (10 mol %)
NH2
NH
+
R1
δ
wmoist CH2Cl2, rt
R1
-I2
I
R1
.
O
X
N-
O
X
N
H
N
3
7
NHR
N
R
I2
NHR
Entry
Substrate
X = O, R = H (3c)
X = NMe, R = H (3e)
X = NEt R = H (3f)
Time (h)
3
Product
% Yielda
X
O
O
X
O
X
C
1
2
3
7a
7b
7c
88
86
87
E
D
3
3
R1
R1
N
a
NH
Isolated yields.
N
-H+
N
R
R
X
O
O
X
5
F
OH
NH2
O
N
OH2
HO
EtOH, HCl
rt, 10 min.
N
HO
+
H2O
N
H+
Path b
NHR
NHR
NHR
O
O
O
O
4a
6a
O
X
O
X
O
X
5a
3
II
I
Scheme 2. Convertion of imine to carbonyl.
R1
NH2
N
O
H
N
F. The unstable enamine F, may immediately isomerize to form the
desired products 5. Formation of the other cyclized product 6 may
be explained through pathway b. In the presence of H+, the propar-
gylic alcohols 3 first form aldols I via regioselective dehydrative
NR
R
4
R1
X
O
O
X
5
6
rearrangement of the alkyne moiety. The
a
,bÀunsaturated ketones
Scheme 3. Possible reaction pathway.
II are formed from I which on 6-‘endo-trig’ Michael-type ring clo-
sure give the products 6.26
5. Ye et al. did not establish the exact pathway from the two prob-
able routes. However, we have carried out further investigation to
identify the more probable one out of the two pathways suggested
Subsequently, a condensation reaction of the aniline derivative
with 6 may give the pyranoquinoline or phenanthroline derivatives

K. C. Majumdar et al. / Tetrahedron Letters 54 (2013) 5586–5590
5589
7. Ife, R. J.; Brown, T. H.; Keeling, D. J.; Leach, C. A.; Meeson, M. L.; Parsons, M. E.;
Reavill, D. R.; Theobald, C. J.; Wiggall, K. J. J. Med. Chem. 1992, 35, 3413.
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105, 218691j; (b) Yamada, N.; Kadowaki, S.; Takahashi, K.; Umezu, K. Biochem.
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R1
O
N
NH2
NR
10 mol % I2, DCM
N
R
x
+
rt. 12 h
O
X
R1
4
X
O
X = O, NEt
6
5
R = Me, Et
R1 = p-Me, m-NO2
Scheme 4. Unsuccessful reaction to find out the reaction pathway.
11. Faber, K.; Strueckler, H.; Kappe, T. J. Heterocycl. Chem. 1984, 21, 1177.
12. Akhmed Khodzhaeva, Kh. S.; Besonova, I. A. Dokl. Akad. Nauk. Uzh. SSR 1982,
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by them. We have conducted a series of reactions of 6 with various
aniline derivatives (4) using 10 mol % I2 in DCM at rt for 12 h
(Scheme 4). But the reaction failed to give product 5. Since, the de-
sired products 5 were not formed by the above mentioned reac-
tions we may conclude that the reactions follow path ‘a’ and
formation of the other cyclized products 6 through pathway ‘b’
and thus, we were able to rule out the involvement of pathway
in the reactions.
16. Bailenger, J. Therapie 1961, 16, 287. Chem. Abstr., 1964, Vol. 60, p. 2222z.
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313.
In conclusion, we have demonstrated a mild and efficient, envi-
ronmentally friendly strategy for the synthesis of potentially bio-
active pyrano[3,2-f]quinoline or phenanthroline derivatives by
molecular iodine-catalyzed tandem reaction of various propargylic
alcoholic derivatives and with or without the use of substituted
amine. The starting materials can be easily prepared and this reac-
tion occurs with a wide range of substrates in high efficiency with
shorter reaction time. While for a similar reaction Ye et al. pro-
posed two pathways for the formation of products, we have been
able to eliminate one and identify the more probable mechanism
for the reaction. The methodology is simple, rapid, and inexpensive
affording high yields of the cyclized products with operational
simplicity.
18. FRG Patent no. 1232156, 1967; Chem. Abstr., 1967, vol. 66, p. 115700b.
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Acknowledgments
23. (a) Majumdar, K. C.; Ponra, S.; Ganai, S. Synlett 2010, 2575; (b) Majumdar, K. C.;
Ponra, S.; Ghosh, D.; Taher, A. Synlett 2011, 104; (c) Majumdar, K. C.; Ponra, S.;
Ghosh, D. Synthesis 2011, 1132; (d) Majumdar, K. C.; Ponra, S.; Nandi, R. K. Eur.
J. Org. Chem. 2011, 6909; (e) Majumdar, K. C.; Ponra, S.; Ghosh, T. RSC Adv. 2012,
2, 1144; (f) Majumdar, K. C.; Ponra, S.; Ghosh, T. Synthesis 2012, 2079; (g)
Majumdar, K. C.; Ponra, S.; Nandi, R. K. Tetrahedron Lett. 2012, 53, 1732.
24. General Procedure for synthesis of 3a–f: To a stirred solution of 6-amino-5-
bromo-2H-chromen-2-one or 6-amino-5-bromo-1-methylquinolin-2(1H)-one
or 6-amino-5-bromo-1-ethylquinolin-2(1H)-one or N-(5-bromo-2-oxo-2H-
chromen-6-yl)acetamide (1 equiv) in DMF (7 mL) and NEt3 (3 mL) 2-methyl
but-3-yn-2-ol (1.2 equiv) was added at room temperature. Then Pd(PPh3)2Cl2
(0.05 equiv) and CuI (0.05 equiv) were to the added under reaction mixture in
nitrogen atmosphere and stirred at 90 °C for 3 h. After completion of the
reaction (monitored by TLC) the reaction mixture was cooled and extracted
with dichloromethane (25 mL Â 3). The combined organic extract was washed
with brine (25 mL Â 4) and dried over Na2SO4. The solvent was distilled off.
The resulting crude product was purified by filtration through a pad of silica gel
(60–120 mesh) using petroleum ether-ethyl acetate mixture as eluent to give
the pure compound (3).
One of us (K.C.M.) is thankful to UGC, (New Delhi) for a UGC
Emeritus Fellowship, and two of us (S.P.) and (T.G.) are grateful
to CSIR, (New Delhi) for senior research fellowships. We also thank
the DST (New Delhi) for providing Bruker NMR spectrometer
(400 MHz) and Perkin–Elmer CHN analyzer, UV–vis spectrometer
and Perkin–Elmer FT-IR under the FIST program.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
07.163.
References and notes
6-(Ethylamino)-5-(3-hydroxy-3-methylbut-1-ynyl)-2H-chromen-2-one:
Yield = 91%, yellow colored solid, mp 72–74 °C. IR (KBr): max = 1701, 2978,
3481 cmÀ1 1H NMR (400 MHz, CDCl3): dH = 1.31 (t, 3H, J = 7.2 Hz), 1.71 (s, 6H),
(3a)
m
1. Balasubramanian, M.; Keay, J. G. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Eds.; Pergamon Press: Oxford, UK,
1996; Vol. 5, pp 245.
.
2.81 (bs, 1H), 3.23 (q, 2H, J = 7.2 Hz), 4.47 (br s, 1H), 6.40 (d, 1H, J = 9.6 Hz), 6.75
(d, 1H, J = 9.2 Hz), 7.14 (d, 1H, J = 9.2 Hz), 7.93 (d, 1H, J = 9.6 Hz). 13C NMR
(100 MHz, CDCl3): dC = 14.7, 31.0, 31.7, 38.3, 65.8, 74.9, 102.3, 106.4, 113.6,
117.0, 117.8, 119.6, 141.9, 145.6, 146.4, 161.3. MS: m/z = 294.06 [M+Na]+. Anal.
Calcd for C16H17NO3: C, 70.83; H, 6.32; N, 5.16; Found: C, 70.68; H, 6.35; N,
5.27.
2. (a) Kim, H. M.; Jin, J.-L.; Lee, C. J.; Kim, N.; Park, K. H. Bull. Chem. Soc. Jpn. 1998,
71, 2945; (b) Jenekhe, S. A.; Lu, L.; Alam, M. M. Macro molecules 2001, 34, 7315;
(c) Agrawal, A. K.; Jenekhe, S. A.; Vanher zeele, H.; Meth, J. S. J. Phys. Chem. 1992,
96, 2837; (d) Jegou, G.; Jenekhe, S. A. Mac romolecules 2001, 34, 7926; (e) Lu, L.;
Jenekhe, S. A. Macromolecules 2001, 34, 6249; (f) Agrawal, A. K.; Jenekhe, S. A.
Chem. Mater. 1996, 8, 579; (g) Jenekhe, S. A.; Zhang, X.; Chen, X. L.; Choong, V.
E.; Gao, Y.; Hsieh, B. R. Chem. Mater. 1997, 9, 409; (h) Zhang, X.; Shetty, A. S.;
Jenekhe, S. A. Macromolecules 1999, 32, 7422; (i) Zhang, X.; Shetty, A. S.;
Jenekhe, S. A. Macromolecules 2000, 33, 2069.
General procedure for the preparation of compound 5a–p:
A mixture of 3 (1 mmol.) and appropriate amine (1 equiv) was dissolved in
dichloromethane 5 mL. Molecular iodine (10 mol %) was added to the stirring
reaction mixture and continued for 30–60 min. After completion of the
reaction as monitored by TLC, the reaction mixture was cooled, extracted
with dichloromethane (3 Â 25 mL) and washed by saturated aqueous sodium
thiosulfate. The combined organic extract was washed with brine solution and
dried over anhydrous Na2SO4. The solvent was distilled off. The crude product
was purified by column chromatography over silica gel (60–120 mesh) using
appropriate petroleum ether–ethyl acetate mixture as eluent to give
compounds (5a–p) and (6a–d).
3. (a) Saito, I.; Sando, S.; Nakatani, K. Bioorg. Med. Chem. 2001, 9, 2381; (b) He, C.;
Lippard, S. J. J. Am. Chem. Soc. 2001, 40, 1414.
4. Cheng, X.-M.; Lee, C.; Klutchko, S.; Winters, T.; Reynolds, E. E.; Welch, K. M.;
Flynn, M. A.; Doherty, A. M. Bioorg. Med. Chem. Lett. 1996, 6, 2999.
5. Anzini, M.; Cappelli, A.; Vomero, S.; Giorgi, G.; Langer, T.; Hamon, M.; Merahi,
N.; Emerit, B. M.; Cagnotto, A.; Skorupska, M.; Mennini, T.; Pinto, J. C. J. Med.
Chem. 1995, 38, 2692.
7-Ethyl-8,8-dimethyl-10-(naphthalen-1-ylimino)-7,8,9,10-tetrahydro-3H-
6. Giardina, G. A. M.; Sarau, H. M.; Farina, C.; Medhurst, A. D.; Grugni, M.;
Raveglia, L. F.; Schmidt, D. B.; Rigolio, R.; Luttmann, M.; Vecchietti, V.; Hay, D.
W. P. J. Med. Chem. 1997, 50, 1794.
pyrano[3,2-f]quinolin-3-one: (5a) Yellow colored solid; mp 172–174 °C,
yield = 92%, IR (KBr): 1564, 1613, 1724 cmÀ1 1H NMR (400 MHz, CDCl3):
.
dH = 1.16 (s, 6H), 1.28 (t, 3H, J = 6.8 Hz), 2.53 (s, 2H), 3.39 (q, 2H, J = 6.8 Hz), 6.39

5590
K. C. Majumdar et al. / Tetrahedron Letters 54 (2013) 5586–5590
(d, 1H, J = 10.0 Hz), 6.76 (d, 1H, J = 7.2 Hz), 6.99 (d, 1H, J = 9.6 Hz), 7.34 (d, 1H,
J = 10.0 Hz), 7.00 (d, 1H, J = 9.6 Hz), 7.36 (d, 1H, J = 9.6 Hz), 9.38 (d, 1H,
J = 10.0 Hz). 13C NMR (100 MHz, CDCl3): dC = 15.3, 24.7, 40.5, 53.0, 58.2, 111.2,
117.7, 118.1, 118.2, 124.2, 142.5, 146.5, 148.8, 160.5, 195.0. MS: m/z = 294
[M+Na]+. Anal. Calcd For C16H17NO3: C, 70.83; H, 6.32; N, 5.16; Found: C, 70.66;
H, 6.38; N, 5.25.
J = 9.6 Hz), 7.40–7.53 (m, 3H), 7.63 (d, 1H, J = 8.0 Hz), 7.78 (d, 1H, J = 8.4 Hz),
7.88 (d, 1H, J = 8.0 Hz), 9.64 (d, 1H, J = 10.0 Hz). 13C NMR (100 MHz, CDCl3):
dC = 15.3, 25.2, 40.4, 42.8, 56.6, 114.1, 116.9, 117.2, 121.0, 123.5, 123.7, 125.7,
125.8, 126.3, 128.0, 143.5, 145.4, 146.3, 146.8, 160.9, 163.8. HRMS: m/z calcd
for C26H24N2O2 [M+H]+: 397.1875; found; 397.1910.
25. Ye, Y.-Y.; Zhao, L.-B.; Zhao, S.-C.; Yang, F.; Liu, X.-Y.; Liang, Y.-M. Chem. Asian J.
2014, 2012, 7.
26. Pisaneschi, F.; Sejberg, J. J. P.; Blain, C.; Ng, W. H.; Aboagye, E. O.; Spivey, A. C.
Synlett 2011, 241.
7-Ethyl-8,8-dimethyl-8,9-dihydro-3H-pyrano[3,2-f]quinoline-3,10(7H)-dione:
(6a) Yield = 6%, light yellow colored solid, mp 156–158 °C. IR (KBr):
m
max = 1514, 1720, 2954, 3108 cmÀ1 1H NMR (400 MHz, CDCl3): dH = 1.32 (t,
.
3H, J = 6.8 Hz), 1.35 (s, 6H), 2.66 (s, 2H), 3.43 (q, 2H, J = 7.36 Hz), 6.47 (d, 1H,