An economical nucleophilic route toward facile synthesis of pyrano[4,3-b]quinolin-1-ones via 6-endo-dig cyclization of o-alkynylquinoline esters

Article abstract of DOI:10.1016/j.tet.2012.12.068

Metal-free facile synthesis of pyrano[4,3-b]quinoline-1-ones is described from methyl 2-arylethynylquinoline-3-carboxylates via intramolecular cyclization in excellent yields. The cyclization reactions are facilitated using cheap and easily available KOH base in MeOH. The reaction conditions did not require dry solvent, inert atmosphere, and avoid further column chromatography purification of the products. These compounds could be further used as building blocks for the synthesis of 2H-benzo[b][1,6]naphthyridin-1-one and 1-chloro-benzo[b][1,6] naphthyridines.

Full text of DOI:10.1016/j.tet.2012.12.068

Tetrahedron 69 (2013) 1822e1829
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An economical nucleophilic route toward facile synthesis
of pyrano[4,3-b]quinolin-1-ones via 6-endo-dig cyclization
of o-alkynylquinoline esters
,
Neha Sharma a, Mrityunjaya Asthana a, Durgesh Nandini b, R.P. Singh b, Radhey M. Singh a
*
a Department of Chemistry, Centre of Advance Studies, Banaras Hindu University, Varanasi, U.P., India
b Centre For Fire, Explosive & Environment Safety(CFEES), DRDO, Timarpur, Delhi 54, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Metal-free facile synthesis of pyrano[4,3-b]quinoline-1-ones is described from methyl 2-arylethynyl-
quinoline-3-carboxylates via intramolecular cyclization in excellent yields. The cyclization reactions are fa-
cilitated using cheap and easily available KOH base in MeOH. The reaction conditions did not require dry
solvent, inert atmosphere, and avoid further column chromatography purification of the products. These
compounds could be further used as building blocks for the synthesis of 2H-benzo[b][1,6]naphthyridin-1-
one and 1-chloro-benzo[b][1,6]naphthyridines.
Received 3 December 2012
Received in revised form 19 December 2012
Accepted 26 December 2012
Available online 3 January 2013
Keywords:
Methyl 2-arylethynylquinoline-3-
carboxylate
Ó 2013 Elsevier Ltd. All rights reserved.
Base mediated
Metal free
Pyrano[4,3-b]quinoline-1-one
2H-Benzo[b][1,6]naphthyridin-1-one
1-Chloro-benzo[b][1,6]naphthyridine
1. Introduction
Recently, Verma et al. have reported the synthesis of similar moiety
in pyrano[4,3-b]quinolinones from the corresponding o-alkynyl
Development of new efficient and economical methodology for
the synthesis of quinoline and their carbo/hetero annelated ana-
logues have attracted great attention from the synthetic as well as
medicinal chemists. Particularly, pyranoquinolines are considered
important class of compounds because their structural units are
component of many alkaloids isolated from Rutaceae family1 for
example, flindersine, oricine, geibalasine, and verprisine.2 Their
derivatives possess variety of applications as drugs, pharmaceuti-
cals and agrochemicals,3 and exhibit significant range of biological
activities, such as anti-allergic, psychotropic, estrogenic, anti-
inflammatory, anticoagulant, coronary constricting, optical bright-
ening, antifungal, and antihistamine activities.4 Consequently,
several methods have been reported for the synthesis of pyr-
anoquinolines.4e,5 In contrast, the synthesis of pyrano[4,3-b]qui-
nolin-1-ones has been less explored. However, the synthesis of 2-
pyrone moiety, the core moiety of analogous isocoumarin de-
rivatives, has been recently reported from transition metals Pd(II),6
Fe(III),7 Cu(II),8 electrophiles,9 and Lewis acid-catalyzed10 inter/
intramolecular cyclization of carboxylic acid and ester derivatives.
esters11 via intramolecular iodocyclization. Similarly, Ghorai et al.
have also reported the synthesis of pyrano[4,3-b]quinolinones from
corresponding 2-alkynylquinoline-3-carboxaldehydes via oxida-
tion followed by intramolecular cyclization.12 However, these
methods have some limitations, such as use of expensive reagents,
anhydrous solvents, longer reaction periods and lower yields.
Recently, our group has been actively engaged in exploring the
reactivity and synthetic applications of 2-chloroquinoline-3-
carboxaldehydes representing two electrophilic centers for their
further reactions. We have demonstrated the synthesis of large
variety of O, N, S-annulated quinolines by the choice of appro-
priate reagents, catalysts, and other reactive partners.13 The easy
accessibility of 3-carboalkoxy14 and 3-carbonitrile15 derivatives
from 2-chloroquinoline-3-carboxaldehydes via oxidation makes
them further attractive intermediates for their synthetic appli-
cations. Recently, we have reported the synthesis of pyrimido-
fused quinolines via different methodology from 2-
chloroquinoline-3-carbonitriles.16 In continuation of these stud-
ies, we now report the facile synthesis of pyrano[4,3-b]quinolin-
1-ones from methyl 2-arylalkynylquinoline-3-carboxylates using
cheap and easily available KOH base in aerobic conditions at room
temperature.
* Corresponding author. Tel.: þ91 542 670 2482; fax: þ91 542 2368127; e-mail
addresses: rmohan@bhu.ac.in, rmohanbhu@gmail.com (R.M. Singh).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.068

N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
Table 1 (continued )
1823
2. Results and discussion
Entry
Substrate
R
Product
Yieldb (%)
Initially, we attempt to optimize the reaction conditions for
the synthesis of methyl 6-methyl-2-phenylethynylquinoline-3-
carboxylate from 2-chloroquinoline-3-carbaldehyde through oxidative
esterification followed by Sonogashira coupling either route A via in-
termediate 2 or vice-versa route B via intermediate 3 (Scheme 1). We
were delighted that the reaction completed within 10 min at room
temperature and afforded 4a in 92% yield via route B (Table 1, entry 1).
We chose route B as our reaction conditions for synthesis of compounds
4aead bearing different substituents on the phenyl ring of arylalkyne
(Table 1, entries 1e5) and 4bei bearing different substituents on quin-
oline nucleus (entries 6e13) and compound 6 (entry 14), respectively.
R0
O
O
N
5
4-F
92
92
89
87
92
88
90
85
F
4ad
O
O
O
N
6
H
H
H
H
H
H
H
H
Route A
(i)
(ii)
78%
O
N
2a
Cl
O
4b
CHO
Cl
89%
O
N
4a
N
CHO
1a
Route B
(iii)
(iv)
O
N
3a
92%
O
O
85%
N
7
6-OMe
7-Me
7-OMe
8-Me
8-Et
Scheme 1. Synthesis of methyl 6-methyl-2-phenylethynylquinoline-3-carboxylate (4)
from 2-choloro-6-methylquinoline-3-carboxaldehyde (1). Conditions: route A: (i) 2-
chloro-6-methylquinoline-3-carboxaldehyde 1a (1.0 mmol), iodine (3.0 mmol),
K2CO3 (3.0 mmol), methanol (3 mL), rt, 10 min (ii) substrate 2a (1.0 mmol), PdCl2
(5 mol %), PPh3 (10 mol %), acetonitrile (3 mL), phenyl acetylene (1.1 mmol), Et3N
(2.0 mmol), 80 ꢀC; route B: (iii) substrate 1a (1.0 mmol), PdCl2 (5 mol %), PPh3
(10 mol %), acetonitrile (3 mL), phenyl acetylene (1.1 mmol), Et3N (2.0 mmol) 80 ꢀC; (iv)
iodine (2.0 mmol), K2CO3 (3.0 mmol), methanol (3 mL), rt, 10 min.
4c
O
O
N
8
Table 1
Synthesis of methyl 2-arylethynylquinoline-3-carboxylates 4a
4d
O
CHO
O
I2/K2CO3
MeOH
rt
R
R
N
N
O
O
R'
Yieldb (%)
R'
O
N
9
Entry
Substrate
Product
4e
R
R0
O
O
O
N
1
6-Me
H
92
O
N
10
11
12
4a
O
4f
O
O
N
N
2
3
3-Me
4-Me
91
92
O
4aa
O
O
N
4g
4ab
O
O
Br
O
O
N
N
6-Br
4
4-OMe
94
O
4h
(continued on next page)
4ac

1824
N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
Table 1 (continued )
10, 11). Among the various solvents examined (entries 12e20),
ethanol and t-BuOH were found equally effective (entries 12 and
13). Other solvents, such as CH3CN and DMF were found less ef-
fective (entries 14, 15). No cyclization reactions occurred in toluene,
benzene, DCM, CHCl3, and water (entries 16e20).
Entry
Substrate
Product
Yieldb (%)
R
R0
H
O
O
To examine the scope of the cyclization reactions, other methyl
2-arylethynyl-quinoline-3-carboxylates 4aead were allowed to
react under the optimized reaction conditions affording the cor-
responding desired cyclized products 5aead in excellent yields
(Table 3, entries 1e5). The electron withdrawing and electron do-
nating groups on phenyl ring in arylalkynes do not affect the yields
of the cyclized products (entries 2e5). Further, examination of cy-
clization reactions of ethyl and n-butyl 6-methyl-2-phenylethynyl-
quinoline-3-carboxylates 4aeeaf under the optimized reaction
conditions afforded the cyclized product 5a in 88% and 84% yields,
respectively (entries 6, 7). Lengthening the alkyl chain of ester
group decreases both reaction rates and yields.
Cl
N
13
7-Cl
87
4i
O
O
14
Ph
H
85
N
6
a
Conditions: substrate 3 (0.5 mmol), 2.0 equiv of I2, and 3.0 equiv of K2CO3, 3 mL
MeOH, rt, 10 min.
b
Yield of isolated product.
Table 3
Synthesis of pyrano[4,3-b]quinolin-1-onea
Next, we optimize the reaction conditions for the intramolecular
cyclization of methyl 2-arylalkynylquinoline-3-carboxylates
affording the synthesis of pyrano[4,3-b]quinolin-1-ones. Initially,
we examined the cyclization reactions of compound 4a using dif-
ferent bases and solvents. Results are summarized in Table 2. The
reaction of 1a (1 mmol) with 2 mL of 20% aq KOH in 2 mL methanol
at room temperature for 1 h afforded the cyclized product 5a in
92%, which was characterized as 8-methyl-3-phenyl-pyrano[4,3-b]
quinolin-1-one from its spectral and analytical data (Table 2, entry
1). Further, decreasing or increasing concentrations of KOH or in-
creasing the temperature of reaction mixture lowered the yield of
the cyclized product (entries 2e4). Similarly, using other bases,
such as NaOH, K3PO4, t-BuOK, K2CO3, and Cs2CO3 did not improve
the yield of product 5a (entries 5e9). No cyclization reaction oc-
curred with organic bases, such as triethylamine and DBU (entries
Entry
Substrate
Product
Time Yieldb
(min) (%)
O
O
O
O
N
N
1
60
60
92%
90%
5a
4a
O
O
O
O
O
O
N
N
N
N
2
3
4
4aa
5aa
O
O
Table 2
O
Optimization of reaction conditions on methyl 6-methyl-2-phenylethynylquinoline-
3-carboxylate with different bases and solventsa (4a)
N
N
N
60
60
92%
94%
O
O
O
O
Base(Aq sol.)
Solvent, rt
4ab
5ab
N
N
O
O
O
4a
5a
O
Entry
Base
Solvent
Time (h)
Yieldb (%)
O
1
2
3
4
5
6
7
8
20% KOH
10% KOH
30% KOH
20% KOH
20% NaOH
20% K3PO4
20% t-BuOK
20% K2CO3
20% Cs2CO3
Et3N
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
t-BuOH
CH3CN
DMF
Toluene
Benzene
DCM
1
6
92
88
85
88c
87
86
85
85
75
Nr
Nr
88
86
70
75
Nr
Nr
Nr
Nr
Nr
4ac
5ac
45 (min)
45 (min)
2
3
3
4
12
48
48
50 (min)
55 (min)
6
2.5
48
48
48
48
48
O
O
O
O
N
5
50
95%
F
F
9
4ad
10
11
12
13
14
15
16
17
18
19
20
5ad
DBU
O
O
20% KOH
20% KOH
20% KOH
20% KOH
20% KOH
20% KOH
20% KOH
20% KOH
20% KOH
O
O
O
N
N
6
7
65
70
88%
84%
4ae
5a
CHCl3
H2O
O
O
O
a
Conditions:methyl 6-methyl-2-phenylethynylquinoline-3-carboxylate (1 mmol),
20% aq base (2 mL/mmol), solvent (2 mL/mmol), rt.
N
N
b
Isolated yields.
Temp 60 ꢀC.
c
4af
5a

N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
1825
Table 3 (continued )
Entry Substrate
To further examine the generality of cyclization reactions, the
reactions of various methyl 2-phenylethynylquinolin-3-carboxyl-
ates 4bei were tested under the optimized reaction conditions. The
reactions proceeded smoothly and afforded the corresponding
pyrano[4,3-b]quinoline-1-ones 5bei in excellent yields (Table 3,
entries 8e15). An electron donating and electron withdrawing
groups at different positions in benzene ring of quinoline moiety do
not show any significant variations in the yields of the products.
However, the reaction rates were found enhanced with electron
withdrawing halogen groups (entries 14, 15) and electron donating
methoxy groups (entries 9,11), which could be attributed to their eI
effects. To further generalize the scope of reactions, pyridine de-
rivative was allowed to react under the optimized reaction condi-
tions and found that the reaction proceeded smoothly affording the
cyclized product 7 in good yield (entry 16).
Product
Time Yieldb
(min) (%)
O
O
O
O
N
N
8
60
92%
4b
5b
O
O
O
O
O
O
N
N
9
55
60
92%
93%
A plausible mechanism for base mediated cyclization is illus-
trated in Scheme 2.
4c
5c
O
O
O
O
N
N
10
4d
5d
O
O
Scheme 2. Plausible mechanism.
O
O
O
N
O
N
Next, the 2-pyrone moiety present in pyrano[4,3-b]quinolin-1-
ones 5 undergo further transformation by choice of suitable re-
agents to afford new class of compounds, providing chemical evi-
dence for the structure of cyclized product 5. Thus, the reaction of
5a with excess of 30% NH4OH in DMF for 6 h or in water for 10 h, at
80 ꢀC afforded compound 8, which was characterized as 2H-benzo
[b][1,6]naphthyridin-1-one from its spectral and analytical data.
The compound 8 was further transformed into 1-chloro-benzo[b]
[1,6]naphthyridine 9 on reaction with POCl3 at reflux temperature
for 4 h (Scheme 3).
11
55
95%
4e
5e
O
O
O
O
O
N
N
N
12
13
60
60
50
89%
90%
94%
4f
5f
O
O
O
N
Scheme 3. Reaction transformations.
4g
5g
Beside spectral data and chemical evidences, single crystal X-ray
crystallographic analysis17 of 5ab was performed to further support
the structure of cyclized products. An ORTEP representation of the
molecule 5ab is given in Fig. 1.
O
O
Br
Br
O
O
O
O
N
N
14
15
4h
5h
O
O
Cl
N
Cl
N
50
60
95%
92%
4i
5i
O
O
O
O
16
N
N
Fig. 1. ORTEP drawing of the X-ray structure of 5ab.
6
7
a
3. Conclusions
Conditions: substrate (1 mmol), 20% aq KOH (2 mL/mmol), MeOH (2 mL/
mmol), rt.
b
Isolated yields.
In conclusion we have developed new methodology for facile
synthesis of pyrano[4,3-b]quinolines using cheap and easily

1826
N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
available KOH base. The procedure is economical avoiding expen-
sive metal catalysts, dry solvent, inert atmosphere, and column
chromatography purifications. We have also explored their appli-
cations to the synthesis of new class of heterocyclic compounds,
such as 1,6-naphthyridone and 1,6-naphthyridine derivatives using
easily available inexpensive reagents.
137.5, 138.7, 142.8, 144.1, 148.8, 156.1, 165.4. Anal. Calcd for
21H17NO2 C, 79.98; H, 5.43; N, 4.44%. Found: C, 79.94; H, 5.40;
N, 4.39%.
C
4.2.4. 2-(4-Methoxy-phenylethynyl)-6-methylquinoline-3-carboxylic
acid methyl ester (4ac). Yellow solid; yield: 94%; mp: 136e138 ꢀC
(d); Rf (10% EtOAc/hexane) 0.50; 1H NMR (300 MHz, CDCl3):
d¼2.59
4. Experimental section
4.1. General
(s, 3H), 3.84 (s, 3H), 4.04 (s, 3H), 6.90 (d, J¼8.1 Hz, 2H), 7.62e7.67
(m, 4H), 8.04 (d, J¼8.4 Hz, 1H), 8.69 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d 21.5, 52.6, 55.3, 87.6, 94.0, 114.1, 118.6, 120.4, 125.4, 127.7,
128.5, 129.1, 132.1, 134.1, 139.9, 142.0, 149.4, 160.4, 165.7. Anal. Calcd
for C21H17NO3C, 76.12; H, 5.17; N, 4.23%. Found: C, 76.10; H, 5.14; N,
4.20%.
Melting points were measured using Buchi Melting-point ap-
paratus in an open capillary tube and are uncorrected. IR spectra
were recorded on VARIAN 3300 FTIR spectrophotometers. 1H
(300 MHz) and 13C (75 MHz) NMR spectra were recorded on JEOL
4.2.5. 2-(4-Fluoro-phenylethynyl)-6-methylquinoline-3-carboxylic
AL 300 MHz spectrometer. The chemical shifts (
d
parts per million)
acid methyl ester (4ad). Yellow solid; yield: 92%; mp: 80e82 ꢀC (d);
and coupling constants (hertz) are reported in the standard
fashion with reference to either internal tetramethylsilane (for 1H)
or the central line (77.0 ppm) of CDCl3 (for 13C). Elemental anal-
yses were performed on Exter Analytical Inc. ‘Model CE-400 CHN
Analyzer’ from Department of Chemistry, BHU, Varanasi. Thin-
layer chromatographies (TLC) were performed on glass plates
(7.5ꢁ2.5 and 7.5ꢁ5.0 cm) coated with Loba Chemie’s silica gel
GF254 and various combinations of ethyl acetate and hexane were
used as eluent. Visualization of spots was accomplished by expo-
sure to UV light. Qualigen’s silica gel (60e120 mesh) was used for
column chromatography (approximately 15e20 g per 1 g of the
crude product).
Rf (10% EtOAc/hexane) 0.55; 1H NMR (300 MHz, CDCl3):
d¼2.56 (s,
3H), 4.04 (s, 3H), 7.08 (d, J¼7.8 Hz, 2H), 7.59e7.73 (m, 4H), 8.17 (d,
J¼8.4 Hz, 1H), 8.81 (s, 1H); 13C NMR (75 MHz, CDCl3):
¼21.6, 52.5,
d
88.3, 92.3, 115.6, 115.9, 118.4, 125.2, 125.8, 126.4, 127.2, 127.9, 128.5,
129.0, 132.2, 139.7, 148.9, 165.4; 19F NMR (282 MHz, CDCl3):
d
¼ꢂ33.007.Anal. Calcd for C20H14NO2 C, 75.22; H, 4.42; N, 4.39%.
Found: C, 75.20; H, 4.38; N, 4.35%.
4.2.6. 2-Phenylethynylquinoline-3-carboxylic acid methyl ester (4b).
Brown solid; yield: 92%; mp 96 ꢀC; Rf (10% EtOAc/hexane) 0.45; 1H
NMR (300 MHz, CDCl3):
d
¼4.03 (s, 3H), 7.39e7.41 (m, 3H), 7.61 (t,
J¼7.5 Hz, 1H), 7.71e7.73 (m, 2H), 7.83 (t, J¼7.2 Hz, 1H), 7.90 (d,
J¼8.1 Hz, 1H), 8.17 (d, J¼8.4 Hz, 1H), 8.81 (s, 1H); 13C NMR (75 MHz,
4.2. General procedure for synthesis of methyl 2-
arylalkynylquinoline-3-carboxylates (4)
CDCl3):
d
¼52.6, 88.4, 93.4, 122.3, 125.4, 125.9, 127.9, 128.5, 128.7,
129.2, 129.4, 132.2, 132.4, 139.8, 141.7, 149.1, 165.6. Anal. Calcd for
C19H13NO2C, 79.43; H, 4.56; N, 4.88%. Found: C, 79.38; H, 4.50; N,
4.84%.
Into a solution of 2-arylalkynylquinoline-3-carbaldehydes 3
(0.50 mmol) in methanol (3 mL/mmol) were added I2 (2 equiv) and
K2CO3 (3 equiv), stirred at room temperature until total disap-
pearance of the starting material as monitored by TLC. The reaction
mixture was then quenched with saturated aq Na2S2O3 (5.0 mL)
and water (5.0 mL). The solid was filtered and washed with water
(3e5 mL) and dried. The crude product was characterized and was
pure enough for further use.
4.2.7. 6-Methoxy-2-phenylethynylquinoline-3-carboxylic acid methyl
ester (4c). Yellow solid; yield: 89%; mp 192 ꢀC; Rf (10% EtOAc/
hexane) 0.52; 1H NMR (300 MHz, CDCl3):
d
¼3.96 (s, 3H), 4.04 (s,
3H), 7.12 (s, 1H), 7.37e7.39 (m, 3H), 7.48 (d, J¼7.2 Hz, 1H), 7.68e7.71
(m, 2H), 8.05 (d, J¼9.0 Hz, 1H), 8.69 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d
¼52.5, 55.6, 88.4, 92.5, 105.5, 122.5, 125.2, 125.8, 127.1,
128.3, 129.1, 130.7, 132.3, 138.2, 139.1, 145.3, 158.8, 165.9. Anal. Calcd
for C20H15NO3 C, 75.70; H, 4.76; N, 4.41%. Found: C, 75.65; H, 4.72;
N, 4.40%.
4.2.1. 6-Methyl-2-phenylethynylquinoline-3-carboxylic acid methyl ester
(4a). Yellow solid; yield: 92%; mp 90 ꢀC; Rf (10% EtOAc/hexane) 0.50;
1H NMR (300 MHz, CDCl3):
d
¼2.56 (s, 3H), 4.03 (s, 3H), 7.39e7.41 (m,
3H), 7.64e7.70 (m, 4H), 8.05 (d, J¼8.7 Hz, 1H), 8.71 (s, 1H); 13C NMR
4.2.8. 7-Methyl-2-phenylethynylquinoline-3-carboxylic acid methyl
ester (4d). Yellow solid; yield: 87%; mp 96e98 ꢀC (d); Rf (10%
(75 MHz, CDCl3):
d¼21.4, 52.5, 87.3, 92.8, 121.4, 122.2, 125.3, 126.0,
127.1, 127.9, 128.4, 129.2, 132.4, 132.9, 139.7, 142.1, 150.9, 165.7. Anal.
Calcd for C20H15NO2: C, 79.72; H, 5.02; N, 4.65%. Found: C, 79.69; H,
5.01; N, 4.60%.
EtOAc/hexane) 0.50; 1H NMR (300 MHz, CDCl3):
d
¼2.56 (s, 3H),
4.03 (s, 3H), 7.40e7.41 (m, 3H), 7.64e7.75 (m, 4H), 8.06 (d, J¼8.7 Hz,
1H), 8.72 (s, 1H); 13C NMR (75 MHz, CDCl3):
d¼21.5, 52.2, 87.3, 93.2,
121.1,122.5,125.6,125.9,126.8,127.9,128.1,129.1,132.4,133.9,139.6,
142.5, 149.9, 165.4. Anal. Calcd for C20H15NO2: C, 79.72; H, 5.02; N,
4.65%. Found: C, 79.69; H, 5.01; N, 4.60%.
4.2.2. 6-Methyl-2-m-tolylethynylquinoline-3-carboxylic acid methyl
ester (4aa). Yellow solid; yield: 91%; mp 118 ꢀC; Rf (10% EtOAc/
hexane) 0.45; 1H NMR (300 MHz, CDCl3):
d
¼2.37 (s, 3H), 2.56 (s,
3H), 4.04 (s, 3H), 7.18e7.29 (m, 3H), 7.51 (d, J¼8.1 Hz, 1H), 7.63e7.66
4.2.9. 7-Methoxy-2-phenylethynylquinoline-3-carboxylic acid methyl
ester (4e). Yellow solid; yield: 92%; mp 150e152 ꢀC (d); Rf (10%
(m, 2H), 8.05 (d, J¼9.0 Hz, 1H), 8.70 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d
¼21.5, 21.6, 52.4, 87.6, 94.0, 121.5, 125.4, 127.2, 128.6, 128.9,
EtOAc/hexane) 0.48; 1H NMR (300 MHz, CDCl3):
d
¼3.97 (s, 3H),
4.03 (s, 3H), 7.39e7.47 (m, 4H), 7.71e7.78 (m, 4H), 8.73 (s, 1H); 13C
NMR (75 MHz, CDCl3):
129.1, 129.8, 131.1, 132.4, 133.1, 137.4, 139.8, 142.5, 144.4, 150.1, 165.4.
Anal. Calcd for C21H17NO2 C, 79.98; H, 5.43; N, 4.44%. Found: C,
79.90; H, 5.41; N, 4.40%.
d¼52.4, 55.7, 88.4, 92.6, 105.4, 122.4, 125.6,
125.9,127.1,128.5,129.4,130.7,132.3, 138.2,140.1,148.3,160.4,166.1.
Anal. Calcd for C20H15NO3: C, 75.70; H, 4.76; N, 4.41%. Found: C,
75.68; H, 4.74; N, 4.40%.
4.2.3. 6-Methyl-2-p-tolylethynylquinoline-3-carboxylic acid methyl
ester (4ab). Yellow solid; yield: 94%; mp 128 ꢀC; Rf (10% EtOAc/
hexane) 0.42; 1H NMR (300 MHz, CDCl3):
d
¼2.37 (s, 3H), 2.54 (s,
4.2.10. 8-Methyl-2-phenylethynylquinoline-3-carboxylic acid methyl
3H), 4.02 (s, 3H), 7.17 (d, J¼7.8 Hz, 2H), 7.57e7.64 (m, 4H), 8.03 (d,
ester (4f). Yellow solid; yield: 88%; mp 66 ꢀC; Rf (10% EtOAc/hex-
J¼8.7 Hz, 1H), 8.68 (s, 1H); 13C NMR (75 MHz, CDCl3):
d
¼21.5,
ane) 0.54; 1H NMR (300 MHz, CDCl3):
d
¼2.84 (s, 3H), 4.02 (s, 3H),
22.3, 52.3, 87.4, 94.0, 120.4, 125.5, 128.5, 129.0, 129.3, 130.1, 131.1,
7.39e7.52 (m, 4H), 7.64e7.69 (m, 4H), 8.73 (s, 1H); 13C NMR

N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
1827
(75 MHz, CDCl3):
d
¼18.1, 52.5, 88.1, 93.4, 121.2, 122.5, 125.3, 126.1,
163.0; Anal. Calcd for C20H15NO2: C 79.72, H 5.02, N 4.65%. Found: C
79.70, H 4.98, N 4.63%.
127.5, 127.9, 128.4, 129.9, 132.1, 132.9, 139.7, 143.2, 150.1, 165.6. Anal.
Calcd for C20H15NO2: C, 79.72; H, 5.02; N, 4.65%. Found: C, 79.70; H,
5.00; N, 4.62%.
4.3.3. 8-Methyl-3-p-tolyl-pyrano[4,3-b]quinolin-1-one (5ab). Yellow
solid; yield: 92%; mp 142 ꢀC; Rf (40% EtOAc/hexane) 0.26; 1H NMR
4.2.11. 8-Ethyl-2-phenylethynylquinoline-3-carboxylic acid methyl
(300 MHz, CDCl3):
d
¼2.38 (s, 3H), 2.57 (s, 3H), 7.17e7.20 (m, 3H),
ester (4g). Yellow solid; yield: 90%; mp 65 ꢀC; Rf (10% EtOAc/hexane)
7.59e7.69(m, 4H), 8.06(d, J¼9.0 Hz,1H), 8.85 (s,1H); 13CNMR(75MHz,
0.55; 1H NMR (300 MHz, CDCl3):
d
¼1.38 (t, J¼7.2 Hz, 3H), 3.35 (q,
J¼7.2 Hz, 2H), 4.02 (s, 3H), 7.35e7.38 (m, 3H), 7.51 (t, J¼7.5 Hz, 1H),
7.64e7.71 (m, 4H), 8.72 (s, 1H); 13C NMR (75 MHz, CDCl3):
CDCl3):
d
¼21.5, 21.7, 101.4, 120.0, 123.5, 125.9, 126.4, 127.3, 128.1, 128.7,
134.8, 136.1, 137.6, 138.0, 147.4, 148.9, 157.0, 163.2; Anal. Calcd for
C20H15NO2: C 79.72, H 5.02, N 4.65%. Found: C 79.70, H 5.00, N 4.62%.
d¼14.7,
24.0, 52.5, 89.0, 92.4, 122.6, 125.2, 125.8, 126.3, 127.7, 128.3, 129.0,
130.3, 132.3, 139.7, 140.2, 143.1, 147.5, 165.9. Anal. Calcd for C21H17NO2:
C, 79.98; H, 5.43; N, 4.44%. Found: C, 79.96; H, 5.40; N, 4.42%.
4.3.4. 3-(4-Methoxy-phenyl)-8-methyl-pyrano[4,3-b]quinolin-1-one
(5ac). Orange solid; yield: 94%; mp 210e212 ꢀC (d); Rf (40% EtOAc/
hexane) 0.23; 1H NMR (300 MHz, CDCl3):
d
¼2.57 (s, 3H), 3.82 (s, 3H),
6.87 (d, J¼9.1 Hz, 2H), 7.64e7.68 (m, 5H), 8.06 (d, J¼9.0 Hz, 1H), 8.86
(s, 1H); 13C NMR (75 MHz, CDCl3):
4.2.12. 6-Bromo-2-phenylethynylquinoline-3-carboxylic acid methyl
ester (4h). Light green solid; yield: 85%; mp 123e124 ꢀC; Rf (10%
d¼21.3, 40.1, 92.9, 102.7, 115.2,
EtOAc/hexane) 0.40; 1H NMR (300 MHz, CDCl3):
d
¼4.05 (s, 3H),
7.39e7.40 (m, 4H), 7.57e8.04 (m, 3H), 8.10 (d, J¼8.7 Hz, 1H), 8.73 (s,
1H); 13C NMR (75 MHz, CDCl3):
125.2, 125.7, 126.2, 126.7, 127.0, 128.8, 131.9, 134.0, 137.6, 138.7, 140.8,
147.2, 166.0; Anal. Calcd for C20H15NO3: C 75.70, H 4.76,N 4.41.
Found: C 75.66, H 4.74, N 4.39.
d¼52.7, 88.4, 92.0, 94.2,122.2,123.0,
125.6, 126.2, 128.4, 129.1, 131.7, 132.3, 134.8, 139.2, 141.9, 148.2,
165.4; Anal. Calcd for C19H12BrNO2: C, 62.32; H, 3.30; N, 3.82%.
Found: C, 62.30; H, 3.26; N, 3.80%.
4.3.5. 3-(4-Fluoro-phenyl)-8-methyl-pyrano[4,3-b]quinolin-1-one
(5ad). Yellow solid; yield: 95%; mp 176 ꢀC; Rf (40% EtOAc/hexane)
0.27; 1H NMR (300 MHz, CDCl3):
d
¼2.57 (s, 3H), 7.06 (d, J¼8.4 Hz,
2H), 7.64e7.69 (m, 3H), 7.84e7.94 (m, 2H), 8.18 (d, J¼8.1 Hz,1H), 8.96
(s, 1H); 13C NMR (75 MHz, CDCl3):
¼22.0, 101.6, 115.7, 120.8, 126.0,
127.2, 128.0, 130.1, 131.4, 131.7, 133.5, 136.4, 137.9, 147.8, 157.6, 161.1,
165.7; 19F NMR (282 MHz, CDCl3):
4.2.13. 7-Chloro-2-phenylethynylquinoline-3-carboxylic acid methyl
ester (4i). White solid; yield: 87%; mp 95 ꢀC; Rf (10% EtOAc/hexane)
d
0.42; 1H NMR (300 MHz, CDCl3):
d
¼4.03 (s, 3H), 7.37e7.45 (m, 4H),
7.73e7.80 (m, 3H), 8.17 (s, 1H), 8.76 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d¼ꢂ32.708. Anal. Calcd for
d
¼52.4, 55.7, 88.9, 93.5, 105.1, 122.4, 125.3, 125.9, 127.2,
C19H12FNO2: C 74.75, H 3.96, N 4.59. Found: C 74.72, H 3.90, N 4.57.
128.5, 129.4, 130.7, 132.2, 138.3, 141.1, 150.3, 160.9, 165.9. Anal. Calcd
for C19H12ClNO2: C, 70.92; H, 3.76; N, 4.35%. Found: C, 70.90; H,
3.72; N, 4.32%.
4.3.6. 3-Phenyl-pyrano[4,3-b]quinolin-1-one(5b). White solid; yield:
92%; mp 152 ꢀC; Rf (40% EtOAc/hexane) 0.38; 1H NMR (300 MHz,
CDCl3):
d
¼7.35 (s, 1H), 7.36e7.40 (m, 3H), 7.64 (t, J¼7.2 Hz, 1H), 7.72
4.2.14. 5-Phenyl-2-phenylethynylnicotinic acidmethyl ester (6). Yellow
solid; yield: 85%; mp 104 ꢀC; Rf (10% EtOAc/hexane) 0.54; 1H NMR
(d, J¼5.7 Hz, 2H), 7.87 (t, J¼7.8 Hz, 1H), 7.94 (d, J¼8.1 Hz, 1H), 8.19 (d,
J¼8.7 Hz, 1H), 8.97 (s, 1H); 13C NMR (75 MHz, CDCl3):
¼103.0, 115.6,
d
(300 MHz, CDCl3):
J¼7.8 Hz, 2H), 7.50e7.52 (m, 2H), 7.64e7.67 (m, 3H), 8.10 (s, 1H), 8.80
(s, 1H); 13C NMR (75 MHz, CDCl3):
d¼4.00 (s, 3H), 7.36e7.38 (m, 3H), 7.42 (d,
122.2, 125.7, 127.2, 128.3, 129.0, 129.6, 130.9, 132.3, 133.9, 141.2, 149.1,
152.4, 157.4, 167.9; Anal. Calcd for C18H11NO2: C 79.11, H 4.06, N 5.13%.
Found: C 79.10, H 4.04, N 5.10%.
d¼52.7, 87.4, 93.4, 122.2, 123.4,
126.7, 127.2, 127.6, 128.1, 128.4, 129.1, 132.3, 134.8, 139.2, 141.9, 152.5,
165.4. Anal. Calcd for C21H15NO2: C, 80.49; H, 4.82; N, 4.47%. Found: C,
80.45; H, 4.80; N 4.44%.
4.3.7. 8-Methoxy-3-phenyl-pyrano[4,3-b]quinolin-1-one (5c). Yellow
solid; yield: 92%; mp 180e182 ꢀC (d); Rf (40% EtOAc/hexane) 0.24; 1H
NMR (300 MHz, CDCl3):
d
¼3.95 (s, 3H), 7.15 (s,1H), 7.30e7.39 (m, 4H),
7.48e7.51 (m, 3H), 7.96 (d, J¼9.3 Hz, 1H), 8.75 (s, 1H); 13C NMR
4.3. General synthetic method for synthesis pyrano[4,5-b]
quinolines-1-one (5)
(75 MHz, CDCl3):
d¼55.5, 105.6, 114.2, 121.0, 126.2, 126.4, 126.7, 127.3,
127.9, 128.1, 129.6, 129.8, 132.1, 140.2, 140.9, 159.0, 166.8. Anal. Calcd
for C19H13NO3: C 75.34, H 4.32, N 4.62%. Found: C 75.20, H 4.30, N
4.60%.
To a solution of 4 (1 mmol) in 2 mL MeOH was added 20% aq
KOH and stirred at room temperature. After completion of the re-
action, monitored by TLC, the reaction mixture was cooled to 0 ꢀC
and dropwise added 10% HCl solution until pH z3, solid product
was filtered, washed with water (3e5 mL) and dried. The products
were recrystallized from methanol.
4.3.8. 7-Methyl-3-phenyl-pyrano[4,3-b]quinolin-1-one(5d). Yellow
solid; yield: 93%; mp 200 ꢀC; Rf (40% EtOAc/hexane) 0.45; 1H NMR
(300 MHz, CDCl3):
d
¼2.61 (s, 3H), 7.35e7.37 (m, 3H), 7.46e7.52 (m,
2H), 7.72 (m, 2H), 7.83 (d, J¼8.1 Hz, 1H), 8.00 (s, 1H), 8.93 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d
¼21.6, 88.3, 92.8, 102.2, 121.9, 123.5, 125.1,
4.3.1. 8-Methyl-3-phenyl-pyrano[4,3-b]quinolin-1-one (5a). Yellow
solid; yield: 92%; mp 129e131 ꢀC; Rf (40% EtOAc/hexane) 0.40; 1H
127.0, 127.8, 128.6, 129.7, 131.7, 139.0, 140.9, 142.4, 148.2, 166.2. Anal.
Calcd for C19H13NO2: C 79.43, H 4.56, N 4.88%. Found: C 79.40, H
4.52, N 4.86%.
NMR (300 MHz, CDCl3):
d
¼2.58 (s, 3H), 7.33e7.36 (m, 4H), 7.62e7.69
(m, 4H), 8.09 (d, J¼9.0 Hz, 1H), 8.87 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d¼21.2, 88.5, 92.4, 103.3, 122.3, 125.1, 125.6, 126.2, 126.9,
4.3.9. 7-Methoxy-3-phenyl-pyrano[4,3-b]quinolin-1-one (5e). Yellow
solid; yield: 95%; mp 205 ꢀC; Rf (40% EtOAc/hexane) 0.44; 1H NMR
127.9, 128.7, 131.9, 134.0, 137.6, 138.6, 147.1, 166.7. Anal. Calcd for
C19H13NO2: C 79.43, H 4.56, N 4.88%. Found: C 79.40, H 4.52, N 4.86%.
(300 MHz, CDCl3):
7.88e7.93 (m, 3H), 7.81 (s, 1H), 8.86 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d¼3.98 (s, 3H), 7.08 (s, 1H), 7.32e7.52 (m, 4H),
4.3.2. 8-Methyl-3-m-tolyl-pyrano[4,3-b]quinolin-1-one (5aa). Yellow
solid; yield: 90%; mp 133 ꢀC; Rf (40% EtOAc/hexane) 0.28; 1H NMR
d
¼55.3, 92.8, 102.2, 114.5, 121.7, 124.5, 125.1, 127.0, 127.9,
128.6, 129.7, 131.7, 139.0, 140.7, 141.9, 158.4, 165.0. Anal. Calcd for
C19H13NO3: C 75.24, H 4.32, N 4.62%. Found: C 75.20, H 4.30, N 4.59%.
(300 MHz, CDCl3):
d
¼2.35 (s, 3H), 2.56 (s, 3H), 6.89e7.15 (m, 4H),
7.47e7.49 (m, 3H), 8.04 (d, J¼9.0 Hz, 1H), 8.80 (s, 1H); 13C NMR
(75 MHz, CDCl3):
d¼21.4, 21.6, 101.6, 120.1, 123.2, 126.0, 126.9, 127.2,
4.3.10. 6-Methyl-3-phenyl-pyrano[4,3-b]quinolin-1-one (5f). Yellow
solid; yield: 89%; mp 145 ꢀC; Rf (40% EtOAc/hexane) 0.38; 1H NMR
128.1, 128.3, 128.4, 133.2, 134.8, 136.3, 137.6, 137.9, 147.4, 148.9, 157.2,

1828
N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
(300 MHz, CDCl3):
d
¼2.87 (s, 3H), 7.39e7.52 (m, 4H), 7.71e7.74 (m,
filtered and washed with water (3e5 mL) and dried. The crude
product was purified by column chromatography using EtOAc/
hexane as eluent to yield pure product as 9.
4H), 7.98 (t, J¼7.5 Hz, 1H), 8.90 (s, 1H); 13C NMR (75 MHz, CDCl3):
d¼19.8, 104.3, 107.4, 115.2, 125.6, 126.7, 127.0, 127.9, 128.7, 128.9,
130.6, 131.6, 133.2, 135.9, 137.1, 140.4, 166.0; Anal. Calcd for
C19H13NO2: C 79.43, H 4.56, N 4.88%. Found: C 79.41, H 4.50, N
4.85%.
4.5.1. 1-Chloro-benzo[b][1,6]naphthyridine (9). Orange solid; yield:
85%; mp 150e152 ꢀC; Rf (15% EtOAc/hexane) 0.54; 1H NMR
(300 MHz, CDCl3):
d
¼2.67 (s, 3H), 7.53e7.56 (m, 4H), 7.95e8.00 (m,
4.3.11. 6-Ethyl-3-phenyl-pyrano[4,3-b]quinolin-1-one (5g). Yellow
solid; yield: 90%; mp 140e142 ꢀC (d); Rf (40% EtOAc/hexane) 0.25;
2H), 8.29 (d, J¼6.6 Hz, 2H), 8.61 (s, 1H), 9.45 (s, 1H); 13C NMR
(75 MHz, CDCl3):
d
¼21.7, 110.7, 114.0, 126.8, 127.3, 128.6, 129.8,
1H NMR (300 MHz, CDCl3):
d
¼1.40 (t, J¼7.2 Hz, 3H), 3.58 (q,
132.3, 133.2,135.1,135.7,138.8, 145.6, 146.0, 148.0,160.3,164.0. Anal.
Calcd for C19H13ClN2: C, 74.88; H, 4.30; N, 9.19%. Found: C, 74.80; H,
4.29; N, 9.16%.
J¼7.2 Hz, 2H), 7.34e7.56 (m, 5H), 7.69e7.76 (m, 4H), 8.90 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d
¼14.7, 24.0, 89.4, 92.9, 122.2, 125.0, 125.8,
126.3, 127.1, 127.9, 129.0, 130.3, 132.5, 139.7, 140.2, 144.1, 149.5,
165.8. Anal. Calcd for C20H15NO2: C 79.72, H 5.02, N 4.65%. Found: C
79.71, H 4.98, N 4.63%.
Acknowledgements
We are thankful to UGC, New Delhi for S.R.F. to N.S., RFSMS
fellowship to M.A. We are also thankful to Vikram Singh, Banaras
Hindu University for his kind help in solving X-ray crystallographic
data.
4.3.12. 8-Bromo-3-(1-methyl-propenyl)-pyrano[4,3-b]quinolin-1-one
(5h). White solid; yield: 94%; mp 148 ꢀC; Rf (40% EtOAc/hexane)
0.42; 1H NMR (300 MHz, CDCl3):
d
¼7.39e7.51 (m, 4H), 7.59e7.98 (m,
3H), 8.15 (m, 2H), 8.89 (s, 1H); 13C NMR (75 MHz, CDCl3):
d
¼88.8,
92.0, 101.4, 122.2, 123.0, 125.7, 126.2, 128.4, 129.0, 131.8, 132.3, 134.8,
138.9, 142.3, 148.0, 165.6; Anal. Calcd for C18H10BrNO2: C 61.39, H
2.86, N 3.98%. Found: C 61.37, H 2.85, N 3.94%.
References and notes
1. (a) Ramesh, M.; Mohan, P. S.; Shanmugam, P. Tetrahedron 1984, 40, 4041; (b)
Grundon, M. F. In The Alkaloids; Brossi, A., Ed.; Academic: London, 1988; Vol. 32,
pp 341e439; (c) Sainsbury, M. In Rodd’s Chemistry of Carbon Compounds; Coffey,
S., Ed.; Elsevier: Berlin, 1978; Vol. IVG, pp 171e225.
4.3.13. 7-Chloro-3-phenyl-pyrano[4,3-b]quinolin-1-one (5i). White
solid; yield: 95%; mp 200 ꢀC; Rf (40% EtOAc/hexane) 0.42; 1H NMR
2. (a) Corrol, R. A.; Orazi, O. O. Tetrahedron Lett.1967, 8, 583; (b) Carling, R. W.; Leeson,
P. D.; Moseley, A. M.; Baker, R.; Forster, A. C.; Grimwood, S.; Kemp, J. A.; Marshall, G.
R. J. Med. Chem. 1992, 35, 1942; (c) Puricelli, L.; Innocenti, G.; Delle Monache, G.;
Caniato, R.; Filippini, R.; Cappelletti, E. M. Nat. Prod. Lett. 2002, 16, 95.
3. (a) Michael, J. P. Nat. Prod. Rep. 1997, 14, 605; (b) Balsubramanian, M.; Keay,
J. G. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5; Chapter 5.06, p 245;
(c) Wright, C. W.; Addac-Kyereme, J.; Breen, A. G.; Brown, J. E.; Cox, M. F.;
Croft, S. L.; Gokcek, Y.; Kendrick, H.; Phillips, R. M.; Pollet, P. L. J. Med. Chem.
2001, 44, 3187; (d) Sahu, N. S.; Pal, C.; Mandal, N. B.; Banerjee, S.; Raha, M.;
Kundu, A. P.; Basu, A.; Ghosh, M.; Roy, K.; Bandyopadhyay, S. Bioorg. Med.
Chem. 2002, 10, 1687; (e) Kournetsov, V. V.; Mendez, L. Y. V.; Gomez, C. M.
M. Curr. Org. Chem. 2005, 9, 141.
4. (a) Yamada, N.; Kadowaki, S.; Takahashi, K.; Umezu, K. Biochem. Pharmacol.
1992, 44, 1211; (b) Faber, K.; Stueckler, H.; Kappe, T. J. Heterocycl. Chem. 1984, 21,
1177; (c) Johnson, J. V.; Rauckmann, B. S.; Baccanari, D. P.; Roth, B. J. Med. Chem.
1989, 32, 1942; (d) Nesterova, I.; Alekseeva, L. M.; Andreeva, L. M.; Golovira, S.
M.; Granic, V. G. Khim. Farm. Zh. 1995, 29, 31; (e) Rajendra Prasad, K. J.; Sekar, M.
J. Nat. Prod. 1998, 61, 294; (f) Mohmed, E. A. Chem. Pap. 1994, 48, 261; Chem.
Abstr. 1995, 123, 9315.
(300 MHz, CDCl3):
d
¼7.32e7.40 (m, 4H), 7.57e7.70 (m, 4H), 8.13 (s,
1H), 8.78 (s, 1H); 13C NMR (75 MHz, CDCl3):
d
¼88.7, 93.8, 102.2,
121.7,123.5,125.5,127.0,127.8,128.6,129.7,133.7,139.0,141.9,144.4,
150.2, 165.8; Anal. Calcd for C18H10ClNO2: C 70.25, H 3.28, N 4.55%.
Found: C 70.22, H 3.25, N 4.50%.
4.3.14. 3,7-Diphenyl-pyrano[4,3-b]pyridin-5-one (7). White solid;
yield: 92%; mp 148 ꢀC; Rf (40% EtOAc/hexane) 0.42; 1H NMR
(300 MHz, CDCl3):
7.54e7.57 (m, 2H), 7.65e7.70 (m, 3H), 8.05 (s, 1H), 8.82 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d¼7.32e7.40 (m, 3H), 7.44 (d, J¼7.8 Hz, 2H),
d
¼101.9, 124.4, 126.5, 127.1, 127.6, 128.4,
128.9, 129.2, 132.4,133.5,134.9,136.1,136.7,151.4,152.5,163.4; Anal.
Calcd for C20H13NO2: C 80.25, H 4.38, N 4.68%. Found: C 80.22, H
4.35, N 4.66%.
5. (a) Desai, M. C.; Thadeio, P. F. Tetrahedron Lett. 1989, 30, 5223; (b) Ashrof, M. A.;
Raman, P. S. J. Indian Chem. Soc. 1992, 69, 690; (c) Cziaky, Z.; Sebok, P. J. Het-
erocycl. Chem. 1994, 31, 701; (d) Plozzi, F.; Venturella, P.; Bellino, A. Gazz. Chim.
Ital. 1969, 99, 711; (e) Subramanian, M.; Mohan, P. S.; Shanmugam, P.; Rajendra
Prasad, K. J. Z. Naturforsch., B: Chem. Sci. 1992, 47, 1016; (f) Duan, X. F.; Zeng, J.;
Zhang, Z. B.; Zi, G. F. J. Org. Chem. 2007, 72, 10283; (g) Bhuyan, P. J.; Baruah, B.;
Kalita, P. K. Tetrahedron Lett. 2006, 47, 7779; (h) Szabo, Z.; Cziaky, Z. J. Heterocycl.
Chem. 1995, 32, 755; (i) Godet, T.; Vaxelaire, C.; Michel, C.; Milet, A.; Belmont, P.
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Chem. 2011, 76, 6789.
4.4. Procedure for synthesis 2H-benzo[b][1,6]naphthyridin-1-
one (8)
To a solution of 5a (1 mmol) in DMF was added excess of 30%
NH4OH 6 h or in water for 10 h and stirred at 80 ꢀC. After com-
pletion of the reaction, monitored by TLC, the reaction mixture was
poured into ice-cold water, solid product was filtered and washed
with water (3e5 mL) and dried. The crude product was character-
ized as 2H-benzo[b][1,6]naphthyridin-1-one.
4.4.1. 8-Methyl-3-phenyl-2H-benzo[b][1,6]naphthyridin-1-one (8).
Green solid; yield: 95%; mp 235e238 ꢀC; Rf (40% EtOAc/hexane)
0.35; 1H NMR (300 MHz, CDCl3):
d
¼2.57 (s, 3H), 7.10 (s, 1H), 7.52 (d,
J¼6.6 Hz, 3H), 7.60e7.75 (m, 4H), 8.03 (d, J¼8.7 Hz, 1H), 8.82 (s, 1H,
D2O exchangeable), 9.14 (s, 1H); 13C NMR (75 MHz, CDCl3):
8. (a) Jithunsa, M.; Ueda, M.; Miyata, O. Org. Lett. 2011, 13, 518;ˇ (b) Inack-Ngi, S.;
Rahmani, R.; Commeiras, L.; Chouraqui, G.; Thibonnet, J.; Duchene, A.; Abarbri, M.;
Parrain, J.-L. Adv. Synth. Catal. 2009, 351, 779; (c) Bryson, T. A.; Stewart, J. J.; Gibson,
J. M.; Thomas, P. S.; Berch, J. K. Green Chem. 2003, 5, 174.
9. Peuchmaur, M.; Lisowski, V.; Gandreuil, C.; Maillard, L. T.; Martinez, J.;
Hernandez, J.-F. J. Org. Chem. 2009, 74, 4158.
10. (a) Bras, G. L.; Hamze, A.; Messaoudi, S.; Provot, O.; Calvez, P.-B. L.; Brion, J.-D.;
Alami, M. Synthesis 2008, 1607; (b) Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.;
Takemoto, Y. J. Org. Chem. 2007, 72, 4468.
11. (a) Verma, A. K.; Rustagi, V.; Aggarwal, T.; Singh, A. P. J. Org. Chem. 2010, 75, 7691;
(b) Verma, A. K.; Aggarwal, T.; Rustagi, V.; Larock, R. C. Chem. Commun. 2010, 4064.
12. Roy, P.; Ghorai, B. K. Tetrahedron Lett. 2012, 53, 235.
d¼21.6,
103.4, 119.5, 125.8, 126.1, 127.3, 127.8, 128.4, 129.5, 130.2, 135.3,
137.4, 140.1, 143.3, 146.7, 147.2, 157.9. Anal. Calcd for C19H14N2O: C,
79.70; H, 4.93; N, 9.78%. Found: C, 79.65; H, 4.90; N, 9.76%.
4.5. Procedure for synthesis 1-chloro-benzo[b][1,6]naphthyr-
idine (9)
13. (a) Singh, R. M.; Singh, M. K.; Chandra, A.; Singh, B. Tetrahedron Lett. 2007, 48,
5987; (b) Singh, R. M.; Singh, B.; Chandra, A.; Upadhyay, S. Tetrahedron Lett.
2008, 49, 6423; (c) Chandra, A.; Singh, B.; Singh, R. M. J. Org. Chem. 2009, 74,
5664; (d) Singh, B.; Chandra, A.; Singh, S.; Singh, R. M. Tetrahedron 2011, 67,
To a solution of 8 (1 mmol) was added POCl3 (1 mL/mmol) and
refluxed. After completion of the reaction, monitored by TLC, the
reaction mixture was poured into ice-cold water, solid product was

N. Sharma et al. / Tetrahedron 69 (2013) 1822e1829
1829
505; (e) Singh, R. M.; Chandra, A.; Singh, B.; Upadhyay, S. Tetrahedron 2008, 64,
11680; (f) Singh, B.; Chandra, A.; Singh, R. M. Tetrahedron 2011, 67, 2441; (g)
Singh, B.; Chandra, A.; Asthana, M.; Singh, R. M. Tetrahedron Lett. 2012, 53, 3242.
14. (a) Srivastava, A.; Singh, R. M. Indian J. Chem., Sect. B 2005, 44, 1868; (b) Larock,
17. Crystal data for 5ab: empirical formula, C20H15NO2; formula weight, 301.33;
crystal color, habit: colorless, block; crystal system, monoclinic; lattice pa-
rameters, a 6.794 (5) b 7.085 (5) c 16.309 (5) Ǻ; V 750.1 (8) Ǻ3; space group Pꢂ1;
Z 2; Dcalcd 1.334 g/cm3; F000 316.0; residuals R 0.065; Rw 0.1714. Crystallo-
graphic data (excluding structure factors) for the structures in this Letter have
been deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 912985. Copies of the data can be obtained
free of charge on an application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [fax: CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: þ441223336033 or
e-mail: deposit@ccdc.cam.ac.uk].
R. C. Comprehensive Organic Transformations:
A Guide to Functional Group
Preparations; VCH: New York, NY, 1988; p 840.
15. Upadhyay, S.; Chandra, A.; Singh, R. M. Indian J. Chem., Sect. B 2009, 48, 152.
16. (a) Chandra, A.; Upadhyay, S.; Singh, B.; Sharma, N.; Singh, R. M. Tetrahedron
2011, 67, 9219; (b) Singh, R. M.; Sharma, N.; Kumar, R.; Asthana, M.; Upadhyay,
S. Tetrahedron 2012, 68, 10318.