One-pot tandem synthesis of Furo[3,2- h ]quinolines by a sonogashira cross-coupling and cyclization reaction supported by basic alumina under microwave irradiation

Article abstract of DOI:10.1055/s-0029-1217143

Acetylenic 8-quinolinols generated in situ by the Sonogashira cross-coupling reaction are efficiently converted into furo[3,2-h]quinolines by microwave-assisted, copper-catalyzed, intramolecular cyclization in the presence of basic alumina. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1217143

486
PAPER
One-Pot Tandem Synthesis of Furo[3,2-h]quinolines by a Sonogashira
Cross-Coupling and Cyclization Reaction Supported by Basic Alumina
Under Microwave Irradiation
O
ne-PotSynth
r
esisof
F
i
uro[3,
t
h
]qui
a
Priyankar Paira, Abhijit Hazra, Diptendu Bhattacharya, Sukdeb Banerjee, Nirup B. Mondal*
Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research,
4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India
Fax +91(33)24735197; E-mail: nirup@iicb.res.in
Received 24 September 2009; revised 20 October 2009
line moiety from a-acetylene derivatives of hydroxyquin-
olines prepared by the Sonogashira cross-coupling
reaction.
Abstract: Acetylenic 8-quinolinols generated in situ by the Sono-
gashira cross-coupling reaction are efficiently converted into fu-
ro[3,2-h]quinolines by microwave-assisted, copper-catalyzed,
intramolecular cyclization in the presence of basic alumina.
Because microwave-assisted reactions have several ad-
Key words: heterocycles, furoquinoline, cross-coupling, cycliza- vantages in comparison with conventional solution-phase
tions, solid-phase synthesis, microwave irradiation
reactions, we contemplated applying such a process for
the synthesis of furo[3,2-h]quinolines. In this communi-
cation, we focus on the use of basic alumina in a one-pot
synthesis of furo[3,2-h]quinolines under environmentally
friendly conditions by microwave irradiation on a solid
support in the presence of copper(I) iodide as a catalyst.
To the best of our knowledge, this is the first report of the
synthesis of furo[3,2-h]quinolines by a copper-catalyzed
coupling in conjunction with a cyclization reaction using
basic alumina.
New versatile and efficient methods for the syntheses of
carbocyclic and heterocyclic1–2 systems in a single opera-
tion are attracting increasing attention on the part of or-
ganic chemists. Heteroannulation of acetylenic
compounds bearing tethered nucleophilic substituents is
one such method that allows the assembly of several flex-
ible building blocks, and this reaction is considered a cor-
nerstone in the design of processes for the rapid
generation of libraries of small drug-like molecules for
high-throughput screening.3 The required acetylenic sub-
strates can be assembled by alkenylation of terminal
alkynes4 (the sp2–sp coupling reaction) with aryl or alke-
nyl halides or triflates in a Sonogashira cross-coupling re-
action, which is one of the most versatile and widely used
reactions for the formation of acetylene derivatives. There
are numerous reports on classical and modified Sonogash-
ira reactions,5–8 and recently many bioactive heterocyclic
molecules, e.g. benzo[b]furans,9 furo[3,2-b]pyridines,
and furo[2,3-b]pyridines,10 have been synthesized by var-
ious metal-catalyzed coupling/cyclization processes using
several inorganic or organic bases, such as potassium tert-
butoxide, cesium carbonate, or triethylamine, in organic
solvents.
We envisaged using 7-halogenated 8-hydroxyquinolines
to prepare various aryl acetylenes that could subsequently
be used in a one-pot, two-step synthesis of furo[3,2-
h]quinolines. At the outset, we chose readily available 5-
chloro-8-hydroxy-7-iodoquinoline (1a) and phenylethyne
as model reaction partners and evaluated the outcomes of
various conditions under microwave irradiation. System-
atic studies of the reaction in the presence of various pal-
ladium catalysts with copper(I) iodide as the cocatalyst in
organic solvents containing various bases showed that a
moderate yield (45%) was obtainable by performing the
reaction in N,N-dimethylformamide (DMF) with palladi-
um(II) acetate/triphenylphosphine as the catalyst and cop-
per(I) iodide as the cocatalyst in the presence of
triethylamine as the base. A prototype reaction without
DMF gave a low yield (20%) of the product, whereas a
similar reaction in DMF in the presence of copper(I) io-
dide and triethylamine in the absence of the palladium cat-
alyst gave an increased yield of 57%. The efficacy of
copper(I) iodide as catalyst prompted us to extend the
study to examine the effects of various solid supports.
The furoquinoline moiety is present in many biologically
active molecules,11 including natural products.12 Such
compounds have previously been prepared by multistep
synthetic operations.13 The biological importance of furo-
quinolines, coupled with our recent success in establish-
ing a basic alumina-supported reaction for forming C–C
bonds by Suzuki–Miyaura cross-coupling under micro-
wave irradiation,14 prompted us to attempt to use the
method for rapid and efficient synthesis of the furoquino-
The results, which are summarized in Table 1, showed
that whereas the use of magnesium oxide, titanium diox-
ide, or montmorillonite K10 as a solid support was unsat-
isfactory, activated carbon as solid support effected
cycloisomerization after the Sonogashira cross-coupling
reaction to yield 63% of the product within 6 min in the
presence of copper(I) iodide as the catalyst (1 mol%) and
triethylamine as the base (entry 10). Changing of template
SYNTHESIS 2010, No. 3, pp 0486–0492
x
x
.
x
x
.2
0
1
0
Advanced online publication: 24.11.2009
DOI: 10.1055/s-0029-1217143; Art ID: P13009SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Tandem Synthesis of Furo[3,2-h]quinolines
487
to silica gel increased the yield to 75% (entry 12), whereas
acidic alumina gave a 78% yield (entry 14), neutral alumi-
na gave an 84% yield (entry 16), and basic alumina gave
a 90% yield (entry 18), even in the absence of triethyl-
amine as a base (entries 20, 21, and 22). Note that reac-
tions with triethylamine as a base in the absence of basic
alumina gave very low yields, even with enhanced load-
ings of the catalyst (entries 24 and 25).
Table 1 Optimization of Catalyst (CuI) Loadings on Various Solid
Supports
Entry Solid supporta
Catalyst Temp
(mol%) (°C)
Time Yieldb
(min) (%)
(A)
1
With Et3N as base
MgO
MgO
TiO2
TiO2
1.0
2.0
1.0
2.0
130
130
130
130
130
130
90
15
15
6
NRc
NR
30
30
38
38
50
52
63
63
63
75
75
78
78
84
84
90
90
2
The good performance of basic alumina may be attribut-
able to its role as a base that leads to the formation of cop-
per acetylides through deprotonation of the alkyne by the
oxide ions of the solid framework14 as shown in
Scheme 1. It is likely that Cu(I) coordinates with the alky-
nyl moiety of substrate, which then undergoes intramolec-
ular nucleophilic attack by the oxygen atom of the 8-
hydroxyquinoline moiety through 5-endo-dig cyclization
in preference to the 4-exo-dig mode of cyclization that
would be expected according to Baldwin’s rules.15 Final-
ly, protodemetalation by hydroxy groups on the surface of
the alumina affords the cycloisomerized product.
3
4
6
5
montmorillonite K10 1.0
montmorillonite K10 2.0
6
6
15
8
7
activated carbon
activated carbon
activated carbon
activated carbon
activated carbon
silica gel
1.0
1.0
1.0
1.0
2.0
1.0
2.0
1.0
2.0
1.0
2.0
1.0
2.0
8
130
110
130
130
130
130
130
130
130
130
130
130
8
9
8
10
11
12
13
14
15
16
17
18
19
(B)
20
21
22
23
(C)
24
25
6
CuI
6
3L
L = alkyne
6
Na
silica gel
6
(
O
O)3Al
L
Ar1
H
acidic alumina
acidic alumina
neutral alumina
neutral alumina
basic alumina
basic alumina
Without Et3N:
basic alumina
basic alumina
basic alumina
basic alumina
With Et3N only:
–
6
Ar1
Ar2
Cu
6
L
I
L
6
L
(
OH
O)3Al
6
L
6
NaI
L
Cu
L
6
C
Cu
L
I
Ar2
Ar1
L
1.0
2.0
0.5
0.1
130
130
130
130
6
6
6
6
90
90
90
72
Ar1
Ar2I
L
Scheme 1 Plausible pathway for the basic alumina-mediated
Sonogashira cross-coupling reaction of 1a and an aralkyne
1.0
2.0
130
130
6
6
20
20
To examine the applicability of this method in the synthe-
sis of other furo[3,2-h]quinolines, we examined the reac-
tions of 5-nitro-7-iodo-8-hydroxyquinoline (1b), 5,7-
dibromo-8-hydroxyquinoline (1c), or 5,7-diiodo-8-hy-
droxyquinoline (1d) with various aryl and heteroaryl
alkynes. Excellent yields were obtained in all cases
(Table 2). The electronic effects of substituents on the
–
a All the reactions were performed by using 1a (10 mmol) and phenyl-
acetylene (10–30 mmol), with CuI as catalyst under microwave irra-
diation at 250 W.
b Isolated yield.
c NR = No reaction.
coupling efficiencies were negligible for both the aryl ha- though the presence of substituents at the ortho or para
lide and the acetylenic reactant. As a result, excellent positions in phenylethyne reactants reduced the yield
yields were obtained from the reaction of the various ha- slightly (entries 3, 4, 7, 9, and 12). Heteroaromatic 2-py-
loquinolines, regardless of the electronic properties of the ridylethynes gave somewhat higher yields (entries 5 and
electrophilic substituents (entries 1, 6, 10, and 14), al- 13).
Synthesis 2010, No. 3, 486–492 © Thieme Stuttgart · New York

488
P. Saha et al.
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Table 2 Sonogashira Cross-Coupling Reaction and Subsequent Intramolecular Cyclization of 8-Hydroxyquinolines with Various Alkynes
Under Microwave Irradiation
R1
Ar
H
R1
basic alumina, CuI
MW, 6 min, 130 °C
R2
Ar
N
O
N
OH
1a R1 = Cl, R2 = I
1b R1 = NO2, R2 = I
1c R1 = R2 = Br
1d R1 = R2 = I
R1 = Cl, NO2,
Ar
Entry
Quinolinea Acetylene
Producta
Yieldb (%)
90
Cl
1
1a
1a
1a
1a
1a
1b
1b
1b
1b
2a
2b
2c
2d
2e
3a
3b
3c
3d
O
N
Cl
Cl
Cl
Cl
2
3
4
5
6
7
8
9
92
85
88
94
92
87
93
90
O
O
N
F
N
F
Cl
F
F
O
O
O
N
N
N
Cl
N
N
NO2
NO2
F
O
O
N
F
NO2
Cl
Cl
N
NO2
F
F
O
N
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One-Pot Tandem Synthesis of Furo[3,2-h]quinolines
489
Table 2 Sonogashira Cross-Coupling Reaction and Subsequent Intramolecular Cyclization of 8-Hydroxyquinolines with Various Alkynes
Under Microwave Irradiation (continued)
R1
Ar
H
R1
basic alumina, CuI
MW, 6 min, 130 °C
R2
Ar
N
O
N
OH
1a R1 = Cl, R2 = I
1b R1 = NO2, R2 = I
1c R1 = R2 = Br
1d R1 = R2 = I
R1 = Cl, NO2,
Ar
Entry
Quinolinea Acetylene
Producta
Yieldb (%)
10
1c
4a
5a
89
O
N
Cl
Cl
11
1d
91
Cl
O
N
F
12
1d
5b
86
F
F
O
N
N
N
13
14
1d
1d
5c
4a
93
90
N
O
N
O
N
a Reaction conditions: basic alumina (500 mg), quinoline (10 mmol), aralkyne (10–30 mmol), CuI (0.5 mol%), microwave irradiation (MW),
130 °C, 6 min.
b Isolated yields. The products were characterized by mass spectrometry and by 1H and 13C NMR spectroscopy.
We also investigated the reusability of basic alumina for change in its activity. To examine the advantages of using
the reaction of 1a with phenylethyne. When the alumina microwave irradiation, we also performed the reaction
was washed with acetone and water and then calcined at with 1a and phenylethyne in an oil bath at 130 °C under
150 °C for five hours, the recovered basic alumina could otherwise identical reaction conditions. It is noteworthy
be recycled three or four times with an insignificant that only a 30% yield of 2a was obtained after 20 hours of
Synthesis 2010, No. 3, 486–492 © Thieme Stuttgart · New York

490
P. Saha et al.
PAPER
ESI-MS: m/z 280 [M + H]+, 282 [M + 2 + H]+, 302 [M + Na]+, 304
reaction, whereas a 90% yield was obtained after micro-
wave irradiation for six minutes.
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H10ClNNaO: 302.0349;
In summary, we have developed a concise and convergent
protocol for preparing various substituted furo[3,2-
h]quinolines by a one-pot process that involves sequential
coupling and cyclization of halogenated 8-hydroxyquino-
lines with alkynes (both of which are readily available) in
the presence of basic alumina under microwave irradia-
tion. The operational simplicity, energy efficiency, and
general applicability of the procedure, as well as reusabil-
ity of the basic alumina, are expected to ensure that of this
chemistry will be extended to the synthesis of other het-
erocyclic compounds of interest.
found: 302.0290.
5-Chloro-2-(3-chlorophenyl)furo[3,2-h]quinoline (2b)
White solid; yield: 92%; mp 179–180 °C; Rf = 0.45 (20% PE–
EtOAc).
IR (KBr, nmax) = 1732, 1579, 1509, 1467, 1437, 1404 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.10 (s, 1 H), 7.36 (m, 2 H), 7.52
(m, 1 H), 7.76 (s, 1 H), 7.82 (d, J = 6.9 Hz, 1 H), 7.96 (s, 1 H), 8.61
(d, J = 8.4 Hz, 1 H), 9.03 (br s, 1 H).
13C NMR (CDCl3, 75 MHz): d = 102.8 (CH), 120.3 (CH), 120.9
(CH), 123.2 (CH), 124.0 (C), 125.1 (CH), 126.4 (C), 128.2 (C),
128.9 (CH), 130.0 (CH), 131.2 (C), 134.0 (CH), 135.0 (C), 136.4
(C), 148.1 (C), 150.6 (CH), 156.2 (C).
IR spectra were recorded on a Jasco FTIR model 410 spectropho-
tometer. 1H spectra were recorded in CDCl3 with TMS as internal
standard on a Bruker 300MHz and 600MHz DPX spectrometers op-
erating at 300 and 600 Hz, respectively; the 13C NMR were similar-
ly recorded at 74.99 and 150 MHz, respectively. ESI (positive-ion)
mass spectra were recorded an using LC-ESI-Q-TOF Micromass
mass spectrometer. Microwave irradiation was performed by using
a mono-mode Discover microwave reactor (CEM Corp., Matthews,
NC, USA), which was used in the Sonogashira cross-coupling reac-
tion and the subsequent intramolecular cyclization. All the chemi-
cals (aralkynes, halogenated 8-hydroxyquinolines, basic alumina,
and catalysts) were purchased from Sigma-Aldrich Co. (Milwau-
kee, WI, USA). Organic solvents for chromatographic purification
were purchased from E. Merck (India) Ltd. (Mumbai, India), and
were of analytical grade. All chromatographic purifications were
performed with silica gel (100–200 mesh) obtained from SRL (New
Delhi, India).
ESI-MS: m/z 314 [M + H]+, 316 [M + 2 + H]+, 336 [M + Na]+, 336
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H9Cl2NNaO: 335.9959;
found: 335.9980.
5-Chloro-2-(4-fluorophenyl)furo[3,2-h]quinoline (2c)
White solid; yield: 85%; mp 178–179 °C; Rf = 0.45 (20% PE–
EtOAc).
IR (KBr, nmax) = 1603, 1495, 1444, 1354, 1233, 1158 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.04 (s, 1 H), 7.15 (t, J = 8.4 Hz,
2 H), 7.52 (dd, J1 = 4.2 Hz, J2 = 8.4 Hz, 1 H), 7.79 (s, 1 H), 7.97 (m,
2 H), 8.62 (d, J = 8.4 Hz, 1 H), 9.03 (br d, J = 3.0 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 101.4 (CH), 115.7 (CH), 116.0
(CH), 120.1 (CH), 120.7 (CH), 123.6 (C), 126.0 (C), 127.0 (CH),
127.1 (CH), 128.2 (C), 133.7 (CH), 136.6 (C), 148.0 (C), 150.6
(CH), 156.6 (C), 161.4 (C), 164.7 (C).
Products 2–5; General Procedure
ESI-MS: m/z 298 [M + H]+, 300 [M + 2 + H]+, 320 [M + Na]+, 322
CHCl3 (10 mL) was added to a mixture of the halogenated 8-hy-
droxyquinoline (10 mmol) and basic alumina (500 mg) in a round-
bottomed flask. The organic layer was evaporated to dryness under
reduced pressure, and the solid mixture was stirred at r.t. for an ad-
ditional 10–15 min to ensure efficient mixing. The aralkyne (10–30
mmol) and CuI (0.5 mol%) were added, the flask was fitted with a
septum, and the mixture irradiated in the microwave reactor at
130 °C (250 W) for 6 min while the reaction was monitored by
TLC. The mixture was then cooled and EtOAc (25 mL) was added,
and the slurry was stirred at r.t. for 10 min. The mixture was vacuum
filtered through a sintered glass funnel and the product was isolated
by flash chromatography.
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H9ClFNNaO: 320.0254;
found: 320.0330.
5-Chloro-2-(2-fluorophenyl)furo[3,2-h]quinoline (2d)
Gray solid; yield: 88%; mp 159–160 °C; Rf = 0.45 (20% PE–
EtOAc).
IR (KBr, nmax) = 2922, 2851,1618, 1581, 1487 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.21 (m, 5 H), 7.49 (m, 1 H), 7.65
(m, 1 H), 7.87 (s, 1 H), 8.33 (t, J = 7.5 Hz, 1 H), 8.66 (d, J = 8.1 Hz,
1 H), 9.05 (d, J = 3 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 106.9 (C), 107.1 (C), 115.9 (CH),
116.2 (C), 120.5 (C), 121.0 (CH), 124.1 (C), 124.4 (C), 124.5 (CH),
126.2 (C), 127.6 (CH), 128.6 (CH), 130.0 (CH), 130.2 (CH), 133.9
(CH), 136.8 (C), 150.7 (CH).
In the recycling experiment, the residue was washed successively
with acetone (3 × 25 mL) and water (3 × 25 mL) and then calcined
at 150 °C. The calcined material could be reused in further coupling
reactions.
5-Chloro-2-phenylfuro[3,2-h]quinoline (2a)
Brown solid; yield: 90%; mp 125–126 °C; Rf = 0.50 (20% PE–
EtOAc).
IR (KBr, nmax) = 2922, 2850, 1610, 1572, 1352 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.16 (s, 1 H), 7.39 (m, 1 H), 7.50
(m, 3 H), 7.85 (s, 1 H), 8.03 (d, J = 7.5 Hz, 2 H), 8.65 (dd, J1 = 1.5
Hz, J2 = 8.7 Hz, 1 H), 9.05 (dd, J1 = 1.5 Hz, J2 = 4.2 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 101.8 (CH), 120.2 (CH), 120.7
(CH), 123.7 (C), 125.2 (CH), 126.1 (C), 128.3 (C), 128.8 (CH),
128.9 (CH), 129.7 (C), 133.8 (CH), 136.8 (C), 148.2 (C), 150.7
(CH), 157.7 (C).
ESI-MS: m/z 298 [M + H]+, 300 [M + 2 + H]+, 320 [M + Na]+, 322
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H9ClFNNaO: 320.0254;
found: 320.0330.
5-Chloro-2-(pyridin-2-yl)furo[3,2-h]quinoline (2e)
Gray solid; yield: 94%; mp 191–192 °C; Rf = 0.55 (20% PE–
EtOAc).
IR (KBr, nmax) = 2924, 2852, 1610, 1573, 1356 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.29 (m, 1 H), 7.57 (dd, J1 = 4.2
Hz, J2 = 8.4 Hz, 1 H), 7.62 (s, 1 H), 7.83 (td, J1 = 1.8 Hz, J2 = 7.8
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One-Pot Tandem Synthesis of Furo[3,2-h]quinolines
491
Hz, 1 H), 7.92 (s, 1 H), 8.24 (d, J = 7.8 Hz, 1 H), 8.69 (m, 2 H), 9.07
(dd, J1 = 4.2 Hz, J2 = 1.2 Hz, 1 H).
13C NMR (CDCl3, 150 MHz): d = 105.2 (CH), 120.2 (CH), 120.8
(CH), 121.2 (CH), 123.4 (CH), 124.4 (C), 126.5 (C), 128.2 (C),
134.0 (CH), 136.9 (C), 137.0 (CH), 148.7 (C), 148.8 (C), 149.9
(CH), 150.8 (CH), 157.0 (C).
1H NMR (600 MHz, CDCl3): d = 7.20 (s, 1 H), 7.41 (m, 4 H), 7.49
(t, J = 7.8 Hz, 2 H), 7.55 (dd, J1 = 4.2 Hz, J2 = 8.4 Hz, 1 H), 7.66
(dd, J1 = 1.8 Hz, J2 = 8.4 Hz, 2 H), 8.06 (m, 3 H), 8.83 (dd, J1 = 1.8
Hz, J2 = 8.4 Hz, 1 H), 9.06 (dd, J1 = 1.8 Hz, J2 = 4.8 Hz, 1 H).
13C NMR (CDCl3, 150 MHz): d = 86.5 (C), 93.6 (C), 102.1 (C),
116.6 (C), 120.8 (CH), 123.1 (C), 124.8 (CH), 125.3 (CH), 126.6
(C), 128.4 (CH), 128.5 (CH), 128.6 (CH), 128.8 (CH), 129.0 (CH),
129.8 (C), 131.6 (CH), 135.4 (CH), 136.6 (C), 149.5 (CH), 150.6
(C), 157.7 (C).
ESI-MS: m/z 281 [M + H]+, 283 [M + 2 + H]+, 303 [M + Na]+, 305
[M + 2 + Na]+.
HRMS (EI): m/z [M + H]+ calcd for C16H10ClN2O: 281.0482; found:
281.0436.
ESI-MS: m/z 346 [M + H]+, 368 [M + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C25H15NNaO: 368.1051 [M +
5-Nitro-2-phenylfuro[3,2-h]quinoline (3a)
Yellow solid; yield: 92%; mp 189–190 °C; Rf = 0.50 (20% PE–
EtOAc).
Na]+; found: 368.1046.
2-(3-Chlorophenyl)-5-[(3-chlorophenyl)ethynyl]furo[3,2-
h]quinoline (5a)
Gray solid; yield: 91%; mp 209–210 °C; Rf = 0.52 (20% PE–
EtOAc).
IR (KBr, nmax) = 2206, 1597, 1506, 1472, 1403 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.21 (s, 1 H), 7.38 (m, 4 H), 7.53
(d, J = 7.2 Hz, 1 H), 7.57 (dd, J1 = 4.2 Hz, J2 = 8.4 Hz, 1 H), 7.64
(s, 1 H), 7.89 (d, J = 7.2 Hz, 1 H), 8.03 (s, 1 H), 8.05 (s, 1 H), 8.77
(dd, J1 = 1.2 Hz, J2 = 8.4 Hz, 1 H) 9.07 (dd, J1 = 1.2 Hz, J2 = 4.2 Hz,
1 H).
IR (KBr, nmax) = 1565, 1525, 1504, 1407, 1316 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47 (m, 4 H), 7.65 (m, 1 H), 8.03
(d, J = 6.9 Hz, 2 H), 8.69 (s, 1 H), 9.12 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 102.3 (CH), 119.2 (C), 120.1 (CH),
122.5 (CH) 125.3 (CH), 126.0 (C), 128.8 (CH), 129.6 (CH), 133.0
(CH), 135.4 (C), 141.7 (C), 151.1 (CH), 151.8 (C), 159.2 (C).
ESI-MS: m/z 291[M + H]+, 313 [M + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H10N2NaO3: 313.0589;
13C NMR (CDCl3, 150 MHz): d = 87.5 (C), 92.2 (C), 103.1 (CH),
116.3 (C), 121.1 (CH), 123.3 (CH), 124.7 (C), 125.1 (2 × CH),
125.2 (CH), 126.8 (C), 128.1 (C), 128.8 (CH), 128.9 (CH), 129.7
(C), 129.8 (CH), 130.1 (CH), 131.4 (CH), 134.4 (C), 135.0 (C),
135.2 (CH), 136.5 (C), 149.8 (C), 150.8 (CH), 156.2 (C).
found: 313.0547.
2-(4-Fluorophenyl)-5-nitrofuro[3,2-h]quinoline (3b)
Yellow solid; yield: 87%; mp 202–203 °C; Rf = 0.50 (20% PE–
EtOAc).
IR (KBr, nmax) = 1606, 1527, 1499, 1409, 1314 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.23 (m, 3 H), 7.67 (dd, J1 = 4.2
Hz, J2 = 8.4 Hz, 1 H), 8.03 (td, J1 = 2.4 Hz, J2 = 5.4 Hz, 2 H), 8.70
(s, 1 H), 9.13 (m, 2 H).
ESI-MS: m/z 414 [M + H]+, 416 [M + 2 + H]+, 436 [M + Na]+, 438
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C25H13Cl2NNaO: 436.0272;
found: 436.0267.
13C NMR (CDCl3, 150 MHz): d = 102.2 (C), 116.2 (CH), 119.4 (C),
121.4 (CH), 125.4 (CH), 126.2 (C), 127.5 (CH), 133.2 (CH), 135.6
(CH), 142.0 (C), 151.4 (CH), 152.0 (C), 158.6 (C), 162.7 (C), 164.4
(C).
ESI-MS: m/z 331 [M + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H9FN2NaO3: 331.0495;
2-(4-Fluorophenyl)-5-[(4-fluorophenyl)ethynyl]furo[3,2-
h]quinoline (5b)
White solid; yield: 86%; mp 239–240 °C; Rf = 0.45 (20% PE–
EtOAc).
IR (KBr, nmax) = 1602, 1502, 1405, 1339, 1299 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.11 (m, 3 H), 7.18 (t, J = 8.4 Hz,
2 H), 7.55 (dd, J1 = 4.2 Hz, J2 = 8.4 Hz, 1 H), 7.60–7.65 (m, 2 H),
8.23 (d, J = 9.6 Hz, 3 H), 8.75 (d, J = 8.4 Hz, 1 H), 9.06 (d, J = 3
Hz, 1 H).
13C NMR (CDCl3, 150 MHz): d = 86.1 (C), 92.5 (C), 101.8 (CH),
115.9 (CH), 116.1 (CH), 116.6 (C), 119.1 (C), 120.8 (CH), 124.8
(CH), 126.4 (C), 127.3 (CH), 128.4 (C), 133.6 (CH), 135.3 (CH),
136.6 (C), 149.5 (C), 150.7 (CH), 156.9 (C), 161.9 (C), 162.3 (C)
163.5 (C).
found: 331.0452.
2-(3-Chlorophenyl)-5-nitrofuro[3,2-h]quinoline (3c)
Yellow solid; yield: 93%; mp 200–201 °C. Rf = 0.45 (20% PE–
EtOAc).
IR (KBr, nmax) = 2919, 2847, 1557, 1523, 1473 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.30 (s, 1 H), 7.43 (m, 2 H), 7.67
(dd, J1 = 3.9 Hz, J2 = 7.2 Hz, 1 H), 7.88 (d, J = 6.6 Hz, 1 H), 8.02
(s, 1 H), 8.68 (s, 1 H), 9.12 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 103.5 (CH), 119.6 (C), 120.1 (CH),
122.8 (CH), 123.5 (CH), 125.3 (CH), 125.8 (C), 129.6 (CH), 130.2
(CH), 130.6 (C), 133.2 (CH), 135.2 (C), 135.6 (C), 142.1 (C), 151.4
(CH), 152.1 (C), 157.8 (C).
ESI-MS: m/z 382 [M + H]+, 404 [M + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C25H13F2NNaO: 404.0863;
found: 404.0789.
2-(Pyridin-2-yl)-5-[(pyridin-2-yl)ethynyl]furo[3,2-h]quinoline
(5c)
Gray solid; yield: 93%; mp 181–182 °C; Rf = 0.45 (20% PE–
EtOAc).
ESI- MS: m/z 325 [M + H]+, 327 [M + 2 + H]+, 347 [M + Na]+, 349
[M + 2 + Na]+.
HRMS (EI): m/z [M + Na]+ calcd for C17H9ClN2NaO3: 347.0199;
found: 347.0222 [M + Na]+.
IR (KBr, nmax) = 2208, 1581, 1506, 1467, 1425, 1341 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.29 (m, 2 H), 7.56 (m, 3 H), 7.74
(m, 2 H), 8.09 (s, 1 H), 8.17 (m, 1 H), 8.65 (br s, 2 H), 8.80 (d,
J = 7.8 Hz, 1 H), 9.02 (br s, 1 H).
2-Phenyl-5-(phenylethynyl)furo[3,2-h]quinoline (4a)
Brown solid; yield: 89% (from 1c) or 90% (from 1d); mp 165–166
°C; Rf = 0.48 (20% PE–EtOAc).
13C NMR (CDCl3, 75 MHz): d = 86.0 (C), 92.8 (C), 105.3 (CH),
115.6 (C), 120.0 (CH), 121.1 (CH), 122.8 (CH), 123.1 (CH), 126.0
IR (KBr, nmax) = 2850, 1606, 1481, 1178, 1074 cm–1.
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(CH), 126.9 (C), 127.1 (CH), 127.8 (C), 135.2 (CH), 136.1 (CH),
136.2 (C), 136.6 (CH), 143.0 (C), 148.3 (C), 149.6 (CH), 149.9
(CH), 150.0 (C), 150.5 (CH), 156.7 (C).
ESI-MS: m/z 348 [M + H]+, 370 [M + Na]+.
HRMS (EI): m/z [M + H]+ calcd for C23H14N3O: 348.1137 [M +
H]+; found: 348.1119: m/z [M + Na]+ calcd for C23H13NaN3O:
370.0956; found: 370.0952.
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Acknowledgment
We thank the Council of Scientific and Industrial Research (CSIR),
New Delhi, for financial support in the form of fellowships to
P. Saha, S. Naskar, R. Paira, S. Mondal, A. Maity, K. B. Sahu,
P. Paira, and A. Hazra. We are also grateful to Dr. B. Achari,
Emeritus Scientist, CSIR, for suggestions and encouragement. Our
special thanks are due to Professor B. C. Ranu of IACS, Kolkata, for
his generous cooperation in utilizing the MW instrument.
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Synthesis 2010, No. 3, 486–492 © Thieme Stuttgart · New York