Synthesis of C3-nitroalkylated-4-hydroxycoumarin and hydroxyiminodihydrofuroquinolinone derivatives via the Michael addition of cyclic 1,3-dicarbonyl compounds to β-nitrostyrenes

Article abstract of DOI:10.1016/j.tet.2011.02.062

Herein, we describe a practical and efficient method for the C3-alkylation of 4-hydroxycoumarin by sonication under 'on water' conditions and mild temperatures using various substituted β-nitrostyrenes. In addition, we report on the development of a conve

Full text of DOI:10.1016/j.tet.2011.02.062

Tetrahedron 67 (2011) 2870e2877
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Synthesis of C3-nitroalkylated-4-hydroxycoumarin and
hydroxyiminodihydrofuroquinolinone derivatives via the Michael addition
of cyclic 1,3-dicarbonyl compounds to b-nitrostyrenes
*
Deepak Kumar Barange, Veerababurao Kavala, Chun-Wei Kuo, Po-Min Lei, Ching-Fa Yao
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein, we describe a practical and efficient method for the C3-alkylation of 4-hydroxycoumarin by
sonication under ‘on water’ conditions and mild temperatures using various substituted -nitrostyrenes.
Received 4 November 2010
Received in revised form 28 January 2011
Accepted 22 February 2011
Available online 26 February 2011
b
In addition, we report on the development of a convenient process for the regioselective synthesis of
angular hydroxyiminodihydrofuroquinolinone catalyzed by base. 4-Hydroxycoumarin and 4-hydroxy-1-
methylquinolin-2(1H)-one reacted smoothly with various nitroolefins to furnish C3-nitroalkylated
hydroxycoumarin derivatives (by sonication and ‘on water’ conditions) and hydroxyiminodihydrofur-
oquinolinone derivatives (ambient condition) as a mixture of Z (minor) and E (major) isomers, re-
spectively. The mild reaction conditions employed, ease of isolation of the products and excellent yields
constitute important features of the methodology.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
core unit of 4-hydroxycoumarin (Fig. 2). The only distinction be-
tween these two structures is that the functionalities at C3 are
Ultrasound irradiation is commonly used in both industry and
academia owing to the green value of harmless acoustic waves.
Sonochemistry1,2 has several advantages in terms of waste re-
duction, energy savings and can avoid the use of high reaction
temperatures. Organic reactions in aqueous media or ‘on water’3,4
have attracted considerable recent interest, primarily because of
environmental and safety issues. The use of water as a solvent in
sonochemistry is good combination from the point of view of green
chemistry. Therefore, to develop a green protocol using ‘on water’
conditions in conjunction with sonication condition would be
highly desirable.
different. Warfarin is an anticoagulant, which may be due to the
presence of coumarin and a ketone group, whereas C3-nitro-
alkylated coumarin also contains a coumarin unit with an aliphatic
nitro group at the C3 position, which could be transformed into
a biologically active compound.
On the other hand, furoquinoline derivatives are an important
class of compounds, because they belong to the known family of
furoquinoline alkaloids, which possess a wide array of biological
properties.8 Among the linear and angular furoquinolinones, an-
gular furoquinolinones8a,9 (Fig. 1, structure 3 and 4) are of interest,
in terms of their synthetic and biological utilities.
Coumarin5 and furoquinoline6 scaffolds are commonly found in
diverse natural products, biologically active compounds and phar-
maceuticals. Amongthe various coumarinderivatives, 3-substituted-
4-hydroxycoumarin has significant biological properties, which in-
clude anti-HIV, anticancer, antibiotic, antiviral and anticoagulants
properties.7 Warfarin7f 1 and coumatetralyl 2 are used for pesticides,
specifically as a rodenticide and an anticoagulant.
Warfarin 1 and C3-nitroalkylated 4-hydroxycoumarin 5 have
some resemblance in terms of functional group arrangement. On
examining the structure of Warfarin and C3-nitroalkylated
4-hydroxycoumarin 5, it is clear that both possess the similar basic
The Michael addition with nitroalkenes is an important CeC
bond forming reaction, which provides easy access to synthetically
important nitroalkanes. During the last decade, our group de-
veloped several methodologies for the Michael addition of nitro-
alkenes10 to various Michael acceptors. We recently reported that
the reaction of nitroalkenes with cyclic 1,3-diketones 6 produced
stereoisomeric hydroxyiminodihydrobenzofurans 7 in the presence
of silica gel in methanol11a under microwave irradiation at 60 ꢀC and
the use of 2-hydroxynaphthoquinone 8 resulted in the generation of
the Michael adduct 9 under ‘on water’ conditions (Scheme 1).11b
These results encouraged us to examine the reaction of nitro-
alkenes with other 1,3-diketones, such as 4-hydroxycoumarin and
4-hydroxy-1-methylquinolin-2(1H)-one. There are several methods
available for the synthesis of C3-alkylated/substituted 4-hydroxy-
coumarin.12,13 However, to our knowledge, there is no direct method
* Corresponding author. Tel.: þ886 2 29309092; fax: þ886 2 29324249; e-mail
address: cheyaocf@ntnu.edu.tw (C.-F. Yao).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.062

D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
2871
Table 1
O
Optimization of reaction condition for C3-alkylation of 4-hydroxycoumarin
OH
OH
NO2
OH
OH
Solvent
NO2
Ph
+
O
O
O
O
Temp, Time
Ph
O
O
2
O
O
1
Coumatetralyl
11a
10
Warfarin
12a
OH
Entry
Solvent
Temp (ꢀC)
Time (h)
Yielda,b (%)
1c
2
Methanol
Water
Water
30
30
80
30
12
12
12
4
n.d.
n.d.
40
O
O
3
4d
Water
95
N
Me
3
O
N
Me
4
O
n.d.¼not detected.
a
All the reactions were carried out using 10 (1.0 equiv) and 11a (1.2 equiv) on
1.0 mmol scale.
almeine
Fig. 1. Biologically active coumarin and angular furoquinolinone derivatives.
(+)-araliopsine
b
Yields were determined from crude 1H NMR spectrum using toluene as an
internal standard.
c
Et3N used as a base (5 mol %).
Sonication condition.
d
However, the best yield was obtained, when the reaction was
performed under ‘on water’ conditions using sonication and these
conditions were chosen for further study (entry 4). The structure of
12a was confirmed by 1H, 13C NMR and its Mass spectrum, and was
further supported by X-ray crystallographic analysis (Fig. 3).
O
N
O
O
OH
OH
O
O
O
O
5
1
C3
4-hydroxycoumarin
-nitroalkylated
Warfarin
Fig. 2. Comparison between warfarin 1 and C3-nitroalkylated 4-hydroxycoumarin 5.
available for the C3-alkylation of 4-hydroxycoumarin with nitro-
alkenes. Similarly, the synthesis of linear and angular furo-
quinolinone derivatives can be achieved via
a number of
methods.8a,9,14 Saito et al. reported on the base catalyzed synthesisof
benzofurans, but they were not able to isolate the cyclic oxime in-
termediate.15 A general method for the synthesis of angular
hydroxyiminodihydrofuroquinolinone has not been reported to
date. Hence, in a continuation of efforts to develop green, efficient
and catalyst-free methodologies16 using nitroalkenes, we wish to
report herein on a study of the reactions of nitroalkenes with 4-
hydroxycoumarin and 4-hydroxy-1-methylquinolin-2(1H)-one un-
der different conditions.
Fig. 3. X-ray crystal structure of 12a (ORTEP diagram).18
To explore the scope and limitations of this methodology, we
examined the reaction of 4-hydroxycoumarin 10 with various
nitroalkenes 11aen under the optimized reaction conditions and
the results are summarized in Table 2.
As indicated, the Michael addition of
b-nitrostyrenes with
7a
4-hydroxycoumarins was efficient in all the cases affording the
corresponding C3-nitroalkylated-4-hydroxycoumarin derivatives
12aen in excellent yields (83e94%). Substituents, such as methyl
(entry 2), methoxy (entries 3e5), chloro, fluoro, trifluoromethyl
and nitro groups (entries 6e11) on the benzene ring of nitroalkenes
were well tolerated under the present reaction conditions. The
C-alkylation of 4-hydroxycoumarin was directed by electronic fac-
8
6
9
7b
tors associated with the
according to the nature of the substituent on the
example, the conjugate addition of 4-hydroxycoumarin to a
b
-nitrostyrenes. The reaction time varied
-nitrostyrene. For
-ni-
Scheme 1. Our previous synthetic approaches using nitroalkenes with cyclic 1,3-di-
carbonyl compounds.
b
b
2. Results and discussion
trostyrene containing electron-donating groups (OCH3 and CH3)
required a longer period of time for completion of the reaction
(entries 2e5). While electron-withdrawing groups (Cl, F, CF3, NO2)
required relatively short reaction time (entries 6e11). 4-Substituted
nitroalkenes afforded good yields and required less time compared
to 2-substituted nitroalkenes. Furthermore acid sensitive sub-
stituents, such as furan and thiophene groups survived under the
present reaction conditions, affording excellent yields (entries 12
and 13). Interestingly, these reaction conditions were equally effi-
cient for the sterically hindered (E)-2-(2-nitrovinyl) naphthalene
In order to initially assess the reactivity of 1,3-dicarbonyl com-
pounds, we examined the reaction of 4-hydroxycoumarin 10
(1 equiv) and nitrostyrene 11a (1.2 equiv) at 30 ꢀC using Et3N as
a basic catalyst in methanol (Table 1, entry 1). Unfortunately, no
products were obtained. In the next experiment, we used ‘on water’
conditions at 30 ꢀC, which was also resulted in no product (entry 2).
When the reaction temperature was increased to 80 ꢀC, we were
delighted to obtain the Michael adduct 12a in 40% yield (entry 3).

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D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
Table 2
Synthesis of 3-substituted 4-hydroxycoumarin derivatives
OH
OH Ar
NO2
Water
NO2
+
Ar
))), 30 oC, Time
O
10
O
O
O
11a-n
12a-n
Entry
1
Ar
Product
Time (h)
6
Yielda,b (%)
90
12a
2
3
12b
12c
10
14
92
83
Scheme 2. Reaction of 4-hydroxycoumarin and (E)-1-methyl-4-(2-nitrovinyl) benzene
in D2O/H2O under sonication at 30 ꢀC.
4
12d
12
87
The D2O experiment supports the conclusion that this reaction
follows the mechanism consistent with that proposed in our pre-
viously reported study.11b
5
6
12e
12f
11
10
94
84
Encouraged by the present results, we replaced the
4-hydroxycoumarin unit with an N-methyl-4-hydroxyquinolinone
moiety, in order to evaluate the reactivity of other 1,3-dicarbonyl
compounds. We initially carried out the reaction of 4-hydroxy-1-
methylquinolin-2(1H)-one 13 with (E)-(2-nitrovinyl)benzene 11a
under sonication ‘on water’ conditions. As expected, we were un-
able to isolate the Michael adduct from this reaction. The Michael
adduct underwent cyclization under sonication ‘on water’ condi-
tions to afford the Z:E isomer of hydroxyiminodihydrofur-
oquinolinone in a ratio of 1:1 with 40% of yield (Table 3, entry 1).
We further proceeded to optimize the reaction to attain suitable
conditions using the reaction of (E)-(2-nitrovinyl) benzene 11a and
4-hydroxy-N-methylquinolinone 13 as a model.
7
12g
9
85
8
12h
12i
8
8
94
91
94
96
9
10
11
12j
9
12k
10
12
13
14
12l
14
14
16
85
88
85
Table 3
Optimization of reaction conditions for the synthesis of hydroxyiminodihy-
droquinolinone derivatives
12m
12n
OH
N
OH
O
Ph
NO2
Cata yst ( acid or base )
l
a
All reactions were carried out using 10 (1.0 equiv) and 11 (1.2 equiv) on
a 2.0 mmol scale under sonication ‘on water’ conditions.
+
N
O
Ph
Solvent
Time
N
O
b
CH3
13
Isolated yields.
CH3
15a
11a
Entry Solvents Acid/Base Temp (ꢀC) Time (h) Yieldsa,e (%) Selectivityc
derivative, affording the corresponding Michael adduct in good
yield (entry 14). All of the products obtained were characterized by
1H NMR, 13C NMR, Mass and IR spectroscopic techniques.
We assumed that the Michael addition of nitrostyrenes with
4-hydroxycoumarin would proceed via the same mechanistic
pathway as was described for the reaction of 2-hydroxynaph-
thoquinone with nitroalkenes.11b In order to confirm the mecha-
nism we examined the Michael addition of 4-hydroxycoumarin 10
(Z:E)
1b
2
Water
Water
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
d
30
80
30
30
30
30
12
12
1
2
1
1
2
12
12
12
30
10
80
78
92
80
5
n.d.
n.d.
n.d.
1: 1
1: 1
1: 9
1: 9
1: 40
1: 4
1: 1
n.d.
n.d.
n.d.
d
3d
4d
5f
Et3N
K2CO3
DIPEA
DABCO
Silica gel 30
TFA
6d
7d
8d
9d
10d
30
30
PTSA
NH2SO3H 30
with the
b-nitrostyrene 11b in D2O under sonication using the
optimized conditions. This reaction afforded a 94% yield of 12b as
*
a deuterated product. A comparison of the 1H and 13C NMR spectra
of the deuterated and non deuterated compounds, one doublet of
n.d.¼not detected.
a
All the reaction were carried out by using 13 (1.0 equiv) and 11a (1.2 equiv) on
1.0 mmol scale.
doublet in 1H NMR spectrum at 5.14 (in
d ppm) appear, which is due
b
Sonication condition.
c
Calculated based on crude 1H NMR.
to the presence of a deuterium atom at the 2-position. Whereas, in
the case of the non deuterated compound one doublet and one
d
20 mol % of acid or base used.
Based on crude 1H NMR yield using toluene as an internal standard.
e
triplet appeared at 5.40 and 5.22 (in
spectrum of the deuterated compound one triplet was observed at
76.3 (in ppm) while, in the case of the non deuterated compound,
only one singlet was observed. A comparison of 1H NMR and 13C
NMR spectra of deuterated product 12b and normal product 12b
d C
ppm), respectively. In the 13
f
10 mol % of DIPEA used.
d
When the reaction was performed in water at 80 ꢀC, only 10% of
the product was obtained in 12 h (Table 3, Entry 2) with a 1:1 se-
lectivity of Z:E isomers. When we next changed the solvent from
water to methanol and the reaction was performed at 30 ꢀC using
*
can be seen in Scheme 2, which indicates that the origin of the
proton is from water.

D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
2873
Et3N/K2CO3, a substantial improvement in the yield and selectivity
(1:9) of Z:E isomers (entries 3 and 4) was observed. The product
yield was drastically increased to 92%, when DIPEA (N,N-diisopro-
pylethylamine, Hunig’s Base) was used, with excellent selectivity
(1:40) of Z:E isomers (entry 5). No significant improvement was
observed when DABCO was used. Using silica gel only 5% of product
was obtained with poor selectivity of Z:E isomers (1:1). Other acid
catalyst, such as TFA, PTSA and NH2SO3H were ineffective for this
conversion.
After having established the optimized reaction conditions for the
formation of hydroxyiminodihydrofuroquinolinones, we explored
the generality and scope of this cyclization process. Thus, 4-hydroxy-
N-methylquinolinone 13 was reacted with a variety of nitroalkenes
14 under the optimized conditions and the results are summarized
in Table 4. As can be seen from Table 4 excellent yields (82e92%) of
the desired hydroxyiminodihydrofuroquinolinone 15 were obtained.
corresponding oxime products. It is noteworthy that we obtained an
inseparablemixtureofE:Zisomers. TheZisomercouldnotbeisolated
in pure form, from mixture of E and Z isomers (entries 5e7) since the
solubilityof the mixtures was very poor. However, it should be noted,
that the mixture underwent a slow isomerization of E isomer to Z
isomer upon heating.
The product assignment was carried out based on a 1H NMR
spectrum of the crude mixture of Z and E isomers. The C3-methine
proton signal in 1H NMR permits the E and Z isomers to be iden-
tified. The C3 proton 1H NMR signal for (Z) isomers appeared in an
upfield region compared to the (E) isomer, which appeared more
downfield. Similarly, chemical shifts for the C]NeOH (oxime)
proton also provide a route to distinguish between the Z and E
isomers. The C]NeOH (oxime) proton in the 1H NMR for the (Z)
isomer was downfield compared to the analogous proton for the (E)
isomer, which appeared at an unfield region in
d ppm. This is in
good agreement with literature reports.17 The 1H NMR chemical
shifts for the C]NeOH (oxime) and C3-methine (CH) proton for the
Z and E isomers are shown in Table 5.
Table 4
Synthesis of angular hydroxyiminodihydrofuroquinolinone derivatives
OH
N
Table 5
O H
O
1H NMR chemical shifts (in
d ppm) for the C]NeOH (oxime) and methine (CH)
Ar
DIPEA ( 10 mol %)
proton signals for Z and E isomers
NO2
14a-g
+
Ar
HO
Methanol
rt, Time
N
O
N
O
N
O
OH
N
CH3
13
CH3
15a-g
O
O
R
R
Entry
1
Ar
Product Time (h) Yielda,b (%) Z:E Selectivityd (%)
N
N
O
15a
15b
15c
15d
1
1
2
2
89
88
83
87
1 : 40
1 : 40
1 : 40
1 : 40
CH3
CH3
2
3
4
(E) isomer (major)
(Z) isomer (minor)
Entry
R
C]NeOH, Methine(CH), C]NeOH, Methine(CH),
(Z isomer) (Z isomer)
(E isomer) (E isomer)
1
2
3
4
5
6
7
C6H5
d
d
10.32
10.28
10.27
10.31
10.31
10.01
10.32
5.40
5.34
5.34
5.35
6.19
5.48
5.58
4-CH3eC6H4
4-OCH3eC6H4
3,4-OCH3eC6H3
2,6-CleC6H3
2-OCH3eC6H4
2-Naphthyl
d
d
5c
6c
15e
0.5
82
1 : 9
d
d
d
d
10.59
10.36
10.62
6.14
5.40
5.50
15f
2
3
84
85
1 : 9
1 : 9
7c
15g
The proton signal for the Z isomeric oxime (C]NeOH) appeared
in a more downfield region compared to the E isomeric oxime
proton, due to intramolecular hydrogen bonding between the OH of
the oxime group and the oxygen of the furan ring of Z-hydroxy-
iminodihydrofuroquinolinone. This also distinguishes the Z isomer
from its counterpart E isomer and was in agreement with obser-
vations reported in the literature (Fig. 4).17b,c
a
All reactions were carried out by using 13 (1.0 equiv) and 14 (1.2 equiv) on
1.0 mmol scale.
b
Isolated yields.
c
Two isomers were inseparable.
d
Z/E selectivity was estimated by crude 1H NMR determination.
O
H
N
OH
Ar
N
As indicted in Table 4, all of the nitroalkenes tested reacted
smoothly with 4-hydroxy-N-methylquinolinone under the present
reaction conditions, affording the corresponding product in excellent
yields. Electronic effects play a significant role in reactions of aro-
matic nitroalkenes. The reaction time depends on the nature of the
O
O
Ar
N
CH3
O
N
CH3
O
substituents on the benzene ring of b-nitrostyrenes. For example, the
E isomer
No hydrogen bonding
Z isomer
Intramolecular hydrogen bonding
reaction involving electron rich nitrostyrene derivatives (4-CH3,
4-OCH3, 3,4-OCH3) required a longer period of time for completion of
the reaction and afforded Z and E isomers in a ratio of (1:40). While
the reaction of nitrostyrenes bearing electron-withdrawing groups
(2,6-Cl) proceeded smoothly within a short reaction time to generate
the corresponding hydroxyiminodihydrofuroquinolinone de-
rivatives in good yields, with Z:E ratio of 1:9. Sterically hindered
nitroalkenes, such as(E)-2-(2-nitrovinyl) naphthalenerequiredmore
time for completion of the reaction (entry 7) to afford the
Fig. 4. Hydrogen bonding in the Z isomer of hydroxyiminodihydrofuroquinolinone.
The structure of the E isomer of hydroxyiminodihydrofuro-
quinolinone was unambiguously confirmed by single crystal X-ray
analysis of 15a shown in Fig. 5.18
A plausible mechanism for the formation of the product is
shown in Scheme 3. Initially, 4-hydroxy-N-methylquinolinone 13

2874
D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
for the synthesis of more complex structures and studies of the
biological activity of these compounds are underway.
4. Experimental
4.1. General
All reactions were performed in oven (130 ꢀC) dried glassware
under an inert atmosphere of argon unless otherwise specified.
Solvents for extraction and chromatography were distilled before
use. All chemicals used in this study were of commercial grade and
were distilled prior to use. Analytical thin layer chromatography
was performed with E. Merck silica gel 60 F254 aluminum plates. All
purifications were carried out by flash chromatography using
230e400 mesh silica gel. 1H and 13C NMR were recorded with
a Bruker Advance EX 400 FT NMR instrument. Chemical shifts are
Fig. 5. X-ray crystal structure of 15a (ORTEP diagram).
reported in parts per million (d) using TMS as the internal standard
and coupling constants are expressed in hertz. Mass spectra were
obtained on a JOEL SX-102A spectrometer at an ionization potential
of 70 eV and data are reported as mass/charge (m/z) with the
percent relative abundance. High-resolution mass spectra (HRMS)
were acquired with a FINNIGAN MAT-95XL spectrometer. The re-
actions were carried out in a thermostated (30ꢁ1 ꢀC) ultrasonic
cleaning bath (Branson Ultrasonics, Ultrasonic bath Model 3010R-
DTH) at 50 kHz frequency. The ultrasonic cleaning bath had an
output of 100 W and a power supply of 335 W.
4.2. General procedure for the C-alkylation of
4-hydroxycoumarin
A mixture of 4-hydroxycoumarin (10) (1 mmol) and b-nitro-
styrene (11) (1.2 mmol) was suspended in 5 mL of water in a 20 mL
vial. The vial was placed into the ultrasonic bath (Branson Ultra-
sonics, Ultrasonic bath Model 3010R-DTH, 50 kHz frequency) at
30 ꢀC for the specific time mentioned in Table 2. The progress of the
reaction was monitored by TLC. After completion of the reaction,
the resulting solid product was filtered and washed with water
(2ꢂ10 mL) and n-hexane (5ꢂ10 mL). Then solid was dried under
vacuum to obtain the product (12aen) in almost pure form in
exellent yields (83e94%).
Scheme 3. Regioselective formation of Angular hydroxyiminodihydrofuroquinolinone
derivatives.19
undergoes C-alkylation with b-nitrostyrenes to give intermediate
II, which would enolize to form intermediates IIIa and IIIb under
basic conditions. This intermediate then proceeds further based on
the reactivity pattern of the carbonyl group. There are two possi-
bilities for intramolecular cyclization. These intermediates can cy-
clize when the C]NO2H is placed at the right position by free
rotation of the sigma bond, and hence controls the regioselectivity
of the reaction. Pathway A could afford the linear hydroxy-
iminodihydrofuroquinolinone IV, which was not observed under
the present conditions. While pathway B proceeds through an
intramolecular cyclization to afford intermediate V, which is then
protonated, undergoes dehydration, followed by nitroso-oxime
tautomerization to furnish the angular hydroxyiminodihydrofuro-
quinolinone derivatives. The possibility of forming other products,
such as 15(i), 15(ii) and 15(iii) was not observed under the present
protocol.
4.3. General procedure for the synthesis of
hydroxyiminodihydrofuroquinolinone derivatives
A
mixture of 4-hydroxy-N-methylquinolin-2(1H)one (13)
(1 mmol) and -nitrostyrene (14) (1.2 mmol) dissolved in 3 mL of
b
methanol. To this solution, 10 mol% of DIPEA was added and the
reaction mixture was stirred at room temperature for the time in-
dicated in the Table 4. The progress of the reaction was monitored
by TLC. After completion of the reaction, water was added, the
resulting solid product was filtered and washed with water
(2ꢂ10 mL) and n-hexane (5ꢂ10 mL). Then solid was dried under
a vacuum to give the product (15aeg) as a mixture of Z and E iso-
mers of angular hydroxyiminodihydrofuroquinolinone in exellent
yields (82e92%).
3. Conclusion
4.4. Spectral data
In summary, we report on the development of a simple and
efficient method for the C-alkylation of 4-hydroxycoumarin de-
rivatives under sonication ‘on water’ conditions using various
4.4.1. 4-Hydroxy-3-(2-nitro-1-phenylethyl)-2H-chromen-2-one
(12a). White solid; mp: 158e160 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3440, 1701,
substituted (phenyl and heteroaryl)
b
-nitrostyrenes. Angular
1607, 1550, 1378. 1H NMR (400 MHz, DMSO-d6)
d
8.01 (d, J¼8.0 Hz,
hydroxyiminodihydrofuroquinolinone derivatives were also syn-
thesized in a regioselective manner under mild conditions at room
temperature. Operational simplicity, inexpensive reagents and
good product yields are the key advantages of the present protocol.
Further work is in progress to extend the scope of this methodology
1H), 7.63 (t, J¼7.8 Hz, 1H), 7.41e7.36 (m, 4H), 7.31 (t, J¼7.3 Hz, 2H),
7.23 (d, J¼7.0 Hz, 1H), 5.46 (dd, J¼14.2, 8.2 Hz, 1H), 5.43 (dd, J¼8.2,
6.8 Hz, 1H), 5.28 (dd, J¼14.2, 6.8 Hz,1H). 13C NMR (100 MHz, DMSO-
d6) d 162.0, 161.9, 152.2, 138.9, 132.4, 128.4, 127.5, 127.0, 124.0, 123.6,
116.3, 115.8, 104.1, 76.5, 38.5. MS (ESI) (m/z) (relative intensity) 334

D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
2875
[(MþNa)þ(70)], 312 [(MþH)þ(58)], 295 (48), 276 (20), 265 (40), 251
(100), 216 (42). HRMS (ESI): calcd for C17H13NO5 [MþH]þ 312.0872,
found 312.0874 and calcd for C18H15NO5Na [MþNa]þ 334.0691,
found 334.0692.
HRMS (ESI): calcd for C18H12NO5F3 [MþH]þ 379.0668, found
379.0779 and calcd for C18H12NO5F3Na (MþNa)þ 402.0565, found
402.0576.
4.4.7. 3-(1-(2-Fluorophenyl)-2-nitroethyl)-4-hydroxy-2H-chromen-
4.4.2. 4-Hydroxy-3-(2-nitro-1-p-tolylethyl)-2H-chromen-2-one
2-one (12g). White solid; mp: 180e181 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3423,
(12b). White solid; mp: 154e156 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3438, 1684,
1700, 1645, 1345, 1275. 1H NMR (400 MHz, DMSO-d6)
d 8.0 (d,
1620, 1520, 1350, 1120. 1H NMR (400 MHz, DMSO-d6)
d
8.03 (d,
J¼7.8 Hz, 1H), 7.64 (t, J¼7.3 Hz, 1H), 7.53 (t, J¼7.6 Hz, 1H), 7.39e7.37
(m, 2H), 7.32e7.27 (m, 1H), 7.17e7.12 (m, 2H), 5.51 (t, J¼7.2 Hz, 1H),
5.43e5.36 (m, 2H). 13C NMR (100 MHz, DMSO-d6) 162.3(d,
JCF¼280 Hz), 161.3, 158.8, 152.3, 132.6, 129.4, 129 (d, JCF¼12 Hz),
125.4, 125.3, 124.3 (d, JCF¼4 Hz), 123.6, 116.4, 115.4 (d, JCF¼24 Hz),
102.6, 75.5, 32.4. MS (ESI): (m/z) (relative intensity) 352
[(MþNa)þ(70)], 330 [(MþH)þ(55)], 312 (78), 283 (40), 269 (70), 249
(30), 216 (100). HRMS (ESI): calcd for C17H12NO5F [MþH]þ
330.0778, found 330.0779 and calcd for C17H12NO5FNa (MþNa)þ
352.0597, found 352.0600.
J¼8.2 Hz, 1H), 7.62 (t, J¼7.8 Hz, 1H), 7.39e7.36 (m, 2H), 7.27 (d,
J¼7.9 Hz, 2H), 7.10 (d, J¼7.8 Hz, 2H), 5.40 (d, J¼7.5 Hz, 2H), 5.22 (t,
J¼7.8 Hz, 1H), 2.24 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
d 161.8,
152.1, 131.1, 135.8, 132.4, 129.0, 127.4, 124.0, 123.5, 116.3, 115.8, 104.3,
76.6, 38.2, 20.5. MS (ESI) (m/z) (relative intensity) 348
[(MþNa)þ(30)], 326 [(MþH)þ(55)], 265 (100), 216 (65). HRMS (ESI):
calcd for C18H15NO5 [MþH]þ 326.1028, found 326.1030 and calcd
for C18H15NO5Na (MþNa)þ 348.0848, found 348.0842.
4.4.3. 4-Hydroxy-3-(1-(2-methoxyphenyl)-2-nitroethyl)-2H-chro-
men-2-one (12c). White solid; mp: 176e177 ꢀC. FT-IR (KBr)
n
/cmꢃ1
8.03
4.4.8. 3-(1-(4-Fluorophenyl)-2-nitroethyl)-4-hydroxy-2H-chromene-
3436, 1650, 1644, 1390, 1215. 1H NMR (400 MHz, DMSO-d6)
d
2-one (12h). White solid; mp: 179e180 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3436,
(d, J¼7.7 Hz, 1H), 7.63 (t, J¼7.6 Hz, 1H), 7.38 (d, J¼7.2 Hz, 1H), 7.24
(dd, J¼6.8, 8.1 Hz, 2H), 6.98 (d, J¼8.0 Hz, 1H), 6.87 (t, J¼7.2 Hz, 1H),
6.87 (t, J¼7.2 Hz, 1H), 5.48 (dd, J¼13.1, 6.7 Hz, 1H), 5.36 (dd, J¼12.8,
9.1 Hz, 1H), 5.16 (dd, J¼9.1, 6.7 Hz, 1H). 13C NMR (100 MHz, DMSO-
1648,1551,1508,1376,1276. 1H NMR (400 MHz, DMSO-d6)
d 8.03 (d,
J¼8.0 Hz, 1H), 7.63 (t, J¼7.8 Hz, 1H), 7.46e7.42, (m, 2H), 7.38e7.35
(m, 2H), 7.14 (t, J¼8.0 Hz, 2H), 5.41 (d, J¼7.9 Hz, 2H), 5.26 (d,
J¼7.9 Hz,1H). 13C NMR (100 MHz, DMSO-d6)
162.4 (d, JCF¼244 Hz),
d
d6)
d
162.2, 161.9, 156.8, 152.2, 132.3, 128.8, 128.2, 127.7, 123.9,
160.0, 152.2, 135.0, 132.5, 129.5 (d, JCF¼13 Hz), 124.0, 123.6 (d,
JCF¼4 Hz), 116.3, 115.8, 115.2 (d, JCF¼24 Hz), 104.0, 76.5, 37.9. MS
(ESI): (m/z) (relative intensity) 352 [(MþNa)þ(80)], 330
[(MþH)þ(40)], 269 (100), 216 (70). HRMS (ESI): calcd for
C17H12NO5F [MþH]þ 330.0778, found 330.0781 and calcd for
C17H12NO5FNa (MþNa)þ 352.0597, found 352.0600.
123.5, 120.1, 116.3, 115.9, 111.0, 102.8, 75.7, 55.5, 33.7. MS (ESI): (m/
z) (relative intensity) 364 [(MþNa)þ(96)], 342 [(MþH)þ (100)].
HRMS (ESI): calcd for C18H15NO6 [MþH]þ 342.0978, found
342.0983 and calcd for C18H15NO6Na [MþNa]þ calcd 364.0797,
found 364.0791.
4.4.4. 4-Hydroxy-3-(1-(3-methoxyphenyl)-2-nitroethyl)-2H-chro-
4.4.9. 3-(1-(4-Chlorophenyl)-2-nitroethyl)-4-hydroxy-2H-chromen-
men-2-one (12d). White solid; mp: 170e171 ꢀC. FT-IR (KBr)
n
/cmꢃ1
2-one (12i). White solid; mp: 181e182 ꢀC. FT-IR (KBr) /cmꢃ1
n
3431, 1695, 1645, 1551, 1420, 1250. 1H NMR (400 MHz, DMSO-d6)
3422, 1715, 1650, 1609, 1520, 1345. 1H NMR (400 MHz, DMSO-d6)
d
8.04 (d, J¼8.0 Hz, 1H), 7.62 (d, J¼7.8 Hz, 1H), 7.37 (d, J¼7.8 Hz, 2H),
d
8.04 (d, J¼7.5 Hz, 1H), 7.64 (t, J¼7.3 Hz, 1H), 7.43e7.36 (m, 6H),
7.21 (d, J¼7.9 Hz, 1H), 7.97e7.95 (m, 2H), 6.82 (d, J¼7.9 Hz, 1H), 5.42
5.44e5.40 (m, 2H), 5.26 (t, J¼7.7 Hz, 1H). 13C NMR (100 MHz,
(d, J¼7.6 Hz, 2H), 5.25 (t, J¼7.7 Hz, 1H), 3.71 (s, 3H). 13C NMR
DMSO-d6)
d 161.8, 152.1, 136.1, 135.8, 132.4, 129.0, 127.4, 124.0,
(100 MHz, DMSO-d6)
d
162.0, 161.8, 159.2, 152.2, 140.3, 132.4, 129.5,
123.5, 116.3, 115.8, 104.3, 76.6, 38.2. MS (ESI) (m/z) (relative in-
tensity) 368 [(MþNa)þ(62)], 346 [(MþH)þ(78)], 348 [(Mþ2) 44],
285 (100), 216 (80). HRMS (ESI): calcd for C17H12NO5Cl [MþH]þ
346.0482, found 346.0484 and calcd for C17H12NO5ClNa (MþNa)þ
368.0302, found 368.0306.
124.0, 123.6, 110.8, 116.3, 115.8, 113.8, 112.0, 104.0, 76.5, 54.9, 38.5.
MS (ESI): (m/z) (relative intensity) 364 [(MþNa)þ(98)], 342
[(MþH)þ (100)], 324 (70), 295 (75). HRMS (ESI): calcd for
C18H15NO6 [MþH]þ 342.0978, found 342.0983 and calcd for
C18H15NO6Na [MþNa]þ calcd 364.0797, found 364.0795.
4.4.10. 4-Hydroxy-3-(2-nitro-1-(4-nitrophenyl)ethyl)-2H-chromen-
4.4.5. 4-Hydroxy-3-(1-(4-methoxyphenyl)-2-nitroethyl)-2H-chro-
2-one (12j). White solid; mp: 180e182 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3443,
men-2-one (12e). White solid; mp: 155e156 ꢀC. FT-IR (KBr)
n
/cmꢃ1
8.02
1714, 1664, 1552, 1346. 1H NMR (400 MHz, DMSO-d6)
d 8.17 (d,
3432, 1644, 1545, 1320, 1150. 1H NMR (400 MHz, DMSO-d6)
d
J¼8.0 Hz, 2H), 8.05 (d, J¼7.5 Hz, 1H), 7.68e7.62 (m, 3H), 7.35 (d,
J¼6.8 Hz, 2H), 5.57e5.55 (m, 1H), 5.43e5.41 (m 2H). 13C NMR
(d, J¼7.8 Hz, 1H), 7.64 (t, J¼7.5 Hz, 1H), 7.38e7.31 (m, 4H), 6.86 (d,
J¼8.1 Hz, 2H), 5.41e5.38 (m, 2H), 5.21 (d, J¼7.44 Hz, 1H), 3.70 (s,
(100 MHz, DMSO-d6)
d 162.6, 161.7, 152.3, 146.7, 146.4, 132.6, 128.8,
3H). 13C NMR (100 MHz, DMSO-d6)
d
161.8, 161.7, 158.8, 156.3, 152.1,
124.1, 123.7, 123.5, 116.5, 115.7, 103.0, 75.7, 38.2. MS (ESI) (m/z)
(relative intensity) 379 [(MþNa)þ(35)], 357 [(MþH)þ(95)], 339 (52),
310 (75), 296 (40). HRMS (ESI): calcd for C17H12N2O5 [MþH]þ
356.0645, found 356.0721 and calcd for C17H12N2O5Na [MþNa]þ
379.0542, found 379.0533.
132.4, 130.7, 128.7, 124.0, 123.6, 116.3, 115.8, 113.8, 104.4, 76.8, 55.0,
37.9. MS (ESI): (m/z) (relative intensity) 364 [(MþNa)þ(45)], 342
[(MþH)þ(40)], 295 (42), 281 (100). HRMS (ESI): calcd for C18H15NO6
[MþH]þ 342.0978, found 342.0979 and calcd for C18H15NO6Na
[MþNa]þ calcd 364.0797, found 364.0791.
4.4.11. 4-Hydroxy-3-(2-nitro-1-(2-nitrophenyl)ethyl)-2H-chromen-
4.4.6. 4-Hydroxy-3-(2-nitro-1-(2-(trifluoromethyl)phenyl)ethyl)-2H-
2-one (12k). White solid; mp: 194e195 ꢀC. FT-IR (KBr)
n
/cmꢃ1 3412,
chromen-2-one (12f). White solid; mp: 195e196 ꢀC. FT-IR (KBr)
n
/
1663, 1619, 1550, 1350. 1H NMR (400 MHz, DMSO-d6)
d 8.04 (d,
cmꢃ1 3424, 1675,1625, 1550, 1490, 1250. 1H NMR (400 MHz, DMSO-
d6)
J¼7.7 Hz, 1H), 7.87 (dd, J¼7.0, 8.0 Hz, 2H), 7.69e7.61 (m, 2H), 7.51 (t,
J¼7.3 Hz, 1H), 7.36 (d, J¼7.8 Hz, 2H), 5.61 (dd, J¼14.0, 8.1 Hz, 1H),
5.53 (dd, J¼8.1, 6.5 Hz, 1H), 5.32 (dd, J¼14.8, 6.5 Hz, 1H). 13C NMR
d
8.07 (d, J¼6.4 Hz, 1H), 7.88 (d, J¼7.2 Hz, 1H), 7.72 (d, J¼7.0 Hz,
1H), 7.64e7.60 (m, 2H), 7.49e7.42 (m, 1H), 7.38e7.32 (m, 2H),
5.57e5.54 (m, 2H), 5.10e5.04 (m, 1H). 13C NMR (100 MHz, DMSO-
(100 MHz, DMSO-d6) d 163.0, 161.9, 152.3, 149.4, 133.0, 132.7, 132.5,
d6)
d
163.2, 161.7, 137.0, 132.6, 132.5 (q, JCF¼32 Hz), 130.6, 127.9,
130.0, 128.6, 124.1, 123.6, 116.7, 115.4, 102.9, 75.6, 34.3. MS (ESI): (m/
z) (relative intensity) 379 [(MþNa)þ(93)], 357 [(MþH)þ(95)], 332
(48), 310 (42), 292 (21), 275 (36), 275 (36), 264 (50), 248 (15), 229
(16). HRMS (ESI): calcd for C17H12N2O5 [MþH]þ 356.0645, found
127.4,126.3 (q, JCF¼272 Hz),125.8, 124.0 (q, JCF¼6.0 Hz), 123.5, 116.4,
115.6, 103.0, 75.9, 35.8. MS (ESI): (m/z) (relative intensity) 402
[(MþNa)þ(90)], 380 [(MþH)þ(65)], 362 (42), 342 (100), 299 (55).

2876
D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
356.0723 and calcd for C17H12N2O5Na [MþNa]þ 379.0542, found
J¼7.4 Hz, 1H), 7.17 (d, J¼8.6 Hz, 2H), 6.83 (d, J¼8.6 Hz, 2H), 5.34 (s,
1H), 3.71 (s, 3H), 3.55 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
165.1,
379.0524.
d
158.2, 157.7,140.4, 136.1,133.0,132.0,128.7,127.9,122.4, 122.2, 115.5,
111.8, 110.1, 45.7, 28.7, 20.5. MS (EI): (m/z) (relative intensity) 320
(Mþ, 100), 303 (45), 287 (22), 274 (18). HRMS (EI): calcd for
C19H16N2O3 (M)þ 320.1161, found 320.1164.
4.4.12. 4-Hydroxy-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2H-chromen-
2-one (12l). Gray solid; mp: 173e174 ꢀC. FT-IR (KBr) /cmꢃ1 3443,
n
1705,1645,1518,1380,1240. 1H NMR (400 MHz, DMSO-d6)
d 8.07 (d,
J¼7.9 Hz, 1H), 7.65 (t, J¼6.8 Hz, 1H), 7.39e7.38 (m, 3H), 7.08 (s, 1H),
6.95 (s, 1H), 5.53 (t, J¼7.5 Hz, 1H), 5.40 (d, J¼8.0 Hz, 2H). 13C NMR
4.4.18. (E)-2-(Hydroxyimino)-3-(4-methoxyphenyl)-5-methyl-2,3-
(100 MHz, DMSO-d6)
d
162.1, 161.5, 152.2, 141.1, 132.6, 126.7, 125.5,
dihydrofuro[3,2-c]quinolin-4(5H)-one (15c). White solid; mp:
125.0, 124.1, 123.7, 116.4, 115.7, 103.5, 77.2, 34.5. MS (ESI): (m/z)
(relative intensity) 318 [(MþH)þ(60)], 271 (20), 257 (98), 216 (15).
HRMS (ESI): calcd for C15H11NO5S [MþH]þ 317.0358, found 317.0438
and calcd for C15H11NO6Na [MþNa]þ 340.0256, found 340.0259.
130e132 ꢀC. FT-IR (KBr) /cmꢃ1 3442, 1690, 1553, 1325, 1135. 1H
n
NMR (400 MHz, DMSO-d6)
d 10.27 (s, C]NeOH, (E) isomer, 1H),
7.87 (d, J¼7.7 Hz, 1H), 7.88 (t, J¼7.8 Hz, 1H), 7.62 (d, J¼8.6 Hz, 1H),
7.39 (t, J¼7.5 Hz, 1H), 7.15e7.06 (m, 4H), 5.34 (s, 1H), 3.54 (s, 3H),
1.98 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
d 165.2, 158.2, 158.1,
4.4.13. 3-(1-(Furan-2-yl)-2-nitroethyl)-4-hydroxy-2H-chromen-2-
157.8, 140.3, 132.0, 129.1, 127.9, 122.4, 122.2, 115.4, 113.6, 111.8, 110.1,
55.0, 45.3, 28.7, 30. MS (EI): (m/z) (relative intensity) 336 (Mþ, 100),
319 (45), 287 (38). HRMS (EI): calcd for C19H16N2O4 (M)þ 336.1110,
found 336.1107.
one (12m). Light green colour; mp: 174e176 ꢀC. FT-IR (KBr)
n
/cmꢃ1
1
3443, 1650, 1600, 1510, 1355, 1215. H NMR (400 MHz, DMSO-d6)
d
8.04 (d, J¼6.8 Hz,1H), 7.65 (s,1H), 7.54 (s,1H), 7.39 (d, J¼6.8 Hz, 2H),
6.39e6.37 (m,1H), 6.26e6.23 (m,1H), 5.37e5.35 (m, 2H), 5.31e5.28
(m, 1H). 13C NMR (100 MHz, DMSO-d6)
162.5, 161.4, 152.3, 151.4,
d
4.4.19. (E)-3-(3,4-Dimethoxyphenyl)-2-(hydroxyimino)-5-methyl-
141.9,132.6,124.1,123.7,116.4,115.8,110.6,106.3,101.3, 75.2, 33.3. MS
(ESI): (m/z) (relative intensity) 301 (Mþ, 100), 437 (38), 324
[(MþNa)þ(98)], 302 [(MþH)þ(58)], 277 (24), 255 (95), 241 (62).
HRMS (ESI): calcd for C15H11NO6 [MþH]þ 302.0665, found 302.0674
and calcd for C15H11NO6Na [MþNa]þ 324.0484, found 324.0479.
2,3-dihydrofuro[3,2-c]quinolin-4(5H)-one (15d). White solid; mp:
166e168 ꢀC. FT-IR (KBr) /cmꢃ1 3435, 1650, 1570, 1390, 1215. 1H
n
NMR (400 MHz, DMSO-d6)
d 10.31 (s, C]NeOH, (E) isomer, 1H),
7.87 (d, J¼7.8 Hz, 1H), 7.74 (t, J¼7.8 Hz, 1H), 7.63 (d, J¼8.6 Hz, 1H),
7.39 (t, J¼7.5 Hz, 1H), 6.95 (s, 1H), 6.83 (d, J¼8.3 Hz, 1H), 6.70 (d,
J¼8.2 Hz, 1H), 5.35 (s, 1H), 3.70 (s, 6H), 3.59 (s, 3H). 13C NMR
4.4.14. 4-Hydroxy-3-(1-(naphthalen-2-yl)-2-nitroethyl)-2H-chro-
(100 MHz, DMSO-d6) d 165.1, 158.1, 157.8, 148.3, 147.9, 140.3, 132.0,
men-2-one (12n). Pale yellow solid; mp: 164e165 ꢀC. FT-IR (KBr)
n
/
128.3, 122.2, 119.7, 115.5, 112.6, 111.8, 111.7, 110.1, 55.5, 45.6, 28.8. MS
(EI): (m/z) (relative intensity) 366 (Mþ, 8), 350 (100), 335 (25).
HRMS (EI): calcd for C20H18N2O5 (M)þ 366.1216, found 366.1227.
cmꢃ1 3435, 1645, 1520, 1312, 1250. 1H NMR (400 MHz, DMSO-d6)
8.01 (d, J¼8.2 Hz,1H), 7.96e7.84 (m 4H), 7.64 (t, J¼8.2 Hz,1H), 7.56
(d, J¼8.2 Hz, 1H), 7.49e7.44 (m, 2H), 7.39e7.38 (m, 2H), 5.61e5.53
(m, 2H) 5.50e5.45 (m, 1H). 13C NMR (100 MHz, DMSO-d6)
162.2,
d
d
4.4.20. 3-(2,6-Dichlorophenyl)-2-(hydroxyimino)-5-methyl-2,3-di-
161.8, 152.2, 136.4, 132.8, 132.5, 132.0, 128.0, 127.7, 127.3, 126.2,
126.0, 125.8,124.0,123.6, 116.3, 115.8,104.0, 76.4, 38.6. MS (ESI): (m/
z) (relative intensity) 384 [(MþNa)þ(45)], 362 [(MþH)þ(75)], 315
(42), 301 (100), 283 (48), 266 (27), 223 (58). HRMS (ESI): calcd for
C21H15NO5 [MþH]þ 362.1028, found 362.1016 and calcd for
C21H15NO5Na [MþNa]þ 384.0848, found 384.0848.
hydrofuro[3,2-c]quinolin-4(5H)-one (15e). White solid; FT-IR (KBr)
n
/cmꢃ1 3434,1674,1520,1332. 1H NMR (400 MHz, DMSO-d6)
d 10.59
(s, C]NeOH, (Z) isomer, 1H), 10.31 (s, C]NeOH, (E) isomer, 1H),
7.89e7.87 (m, (E) isomer and (Z) isomer, 2H), 7.78e7.74 (m, (E)
isomer and (Z) isomer, 2H), 7.64e7.62 (m, (E) isomer and (Z) isomer,
2H), 7.55e7.52 (m, (E) isomer, 1H), 7.41e7.36 (m, (E) isomer and (Z)
isomer, 2H), 7.31e7.30 (m, (E) isomer, 2H), 6.19 (s, (E) isomer, 1H),
6.14 (s, (E) isomer, 1H), 3.56 (s, (Z) isomer, 3H), 3.54 (s, (E) isomer,
4.4.15. Deuterated compound of (12b
120e122 ꢀC. FT-IR (KBr) /cmꢃ1 3429, 2920, 1671, 1209, 552. 1H
NMR (400 MHz, DMSO-d6)
7.75 (d, J¼7.8 Hz, 1H), 7.55 (t, J¼7.8 Hz,
1H), 7.33e7.30 (m, 4H), 7.17 (d, J¼7.6 Hz, 2H), 5.14 (dd, J¼13.1,
6.9 Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz, DMSO-d6)
167.7, 161.7,
*
). Yellow solid; mp:
n
3H). 13C NMR (100 MHz, DMSO-d6)
d 162.2, 158.4, 156.4, 157.7, 137.6,
d
137.2, 132.1,130.0, 129.2, 129.1, 128.4, 128.2, 128.1,127.9, 127.8, 126.6,
124.4, 122.7, 119.0, 116.8, 115.8, 92.1, 85.0, 30.4, 30.1, 29.5, 29.2. MS
(EI) (m/z) (relative intensity) 376.0 (Mþ2, 65), 374 (Mþ, 100), 323
(22), 296 (40), 248 (70). HRMS (EI): calcd for C18H12N2O3Cl2 (M)þ
374.0219, found 374.0231.
d
152.1, 136.2, 135.8, 132.4, 129.0, 127.4, 124.0, 123.5, 116.3, 115.7,
104.3, 76.3 (t, J¼21.0 Hz), 38.1, 20.5. MS (ESI) (m/z) (relative in-
tensity) 265 (8), 325 (14), 326(Mþ, 20). HRMS (ESI): calcd for
C18H14DNO5 (MþH)þ 326.1013 found 326.1004 and for
C18H14DNNaO5 (MþNa)þ 349.0911 found 349.0916.
4.4.21. 2-(Hydroxyimino)-3-(2-methoxyphenyl)-5-methyl-2,3-dihy-
drofuro[3,2-c]quinolin-4(5H)-one (15f). White solid; FT-IR (KBr) v/
cmꢃ1 3443, 1678, 1544, 1335, 113. 1H NMR (400 MHz, DMSO-d6)
4.4.16. (E)-2-(Hydroxyimino)-5-methyl-3-phenyl-2,3-dihydrofuro
d 10.36 (s, C]NeOH, (Z) isomer, 1H), 10.01 (s, C]NeOH, (E) isomer,
[3,2-c]quinolin-4(5H)-one (15a). White solid; mp: 140e142 ꢀC. FT-
1H,), 7.89e7.87 (m, (E) isomer and (Z) isomer, 2H), 7.75e7.71 (m, (E)
isomer and (Z) isomer, 2H), 7.40e7.37 (m, (E) isomer and (Z) isomer,
2H), 7.25e7.17 (m, (E) isomer and (Z) isomer, 4H), 6.99e6.86 (m, (E)
isomer and (Z) isomer, 4H), 5.48 (s, (E) isomer,1H), 5.40 (s, (Z) isomer,
1H), 3.66 (s, (Z) isomer, 3H), 3.62 (s, (E) isomer, 3H), 3.55 (s, (Z)
isomer, 3H), 3.52 (s, (E) isomer, 3H). 13C NMR (100 MHz, DMSO-d6)
IR (KBr)
(400 MHz, DMSO-d6)
n
/cmꢃ1 3431, 1685, 1602, 1551, 1335, 1135. 1H NMR
d
10.32 (s, C]NeOH, (E) isomer, 1H), 7.88 (d,
J¼6.4 Hz, 1H), 7.75 (t, J¼7.2 Hz, 1H), 7.63 (d, J¼8.0 Hz, 1H), 7.40 (t,
J¼7.2 Hz, 1H), 7.28e7.21 (m, 5H), 5.40 (s, 1H), 3.55 (s, 3H). 13C NMR
(100 MHz, DMSO-d6)
d 165.0, 158.3, 157.9, 140.2, 136.0, 132.1, 128.2,
128.0, 126.9, 122.4, 122.2, 115.5, 111.7, 110.1, 46.1, 28.8. MS (EI): (m/z)
(relative intensity) 306 (Mþ, 100), 289 (35), 248 (22). HRMS (EI):
calcd for C18H14N2O4 (M)þ 306.1004, found 306.1006.
d 165.3, 158.5, 158.0, 157.8, 157.0, 156.9, 140.2, 135.0, 134.9, 131.8,
131.6, 128.6, 128.3, 127.6, 125.0, 124.6, 122.2, 122.1, 120.4, 120.1, 115.4,
115.4, 111.8, 111.4, 110.2, 55.9, 55.8, 55.6, 28.8, 28.7, 28.6. MS (EI): (m/
z) (relative intensity) 336 (Mþ, 22), 320 (100), 288 (35), 262 (28).
HRMS (EI): calcd for C19H16N2O4 (MþH)þ 336.1105, found 336.1104.
4.4.17. (E)-2-(Hydroxyimino)-5-methyl-3-p-tolyl-2,3-dihydrofuro
[3,2-c]quinolin-4(5H)-one (15b). White solid; mp: 165e167 ꢀC. FT-
IR (KBr)
(400 MHz, DMSO-d6)
J¼6.8 Hz, 1H), 7.77e7.75 (m, 1H), 7.63 (d, J¼8.6 Hz, 1H), 7.39 (t,
n
/cmꢃ1 3438, 1687, 1630, 1556, 1335, 1125. 1H NMR
4.4.22. 2-(Hydroxyimino)-5-methyl-3-(naphthalen-2-yl)-2,3-dihy-
d
10.28 (s, C]NeOH, (E) isomer, 1H), 7.87 (d,
drofuro[3,2-c]quinolin-4(5H)-one (15g). White solid; FT-IR (KBr)
n/
cmꢃ1 3422, 1670, 1638, 1548, 1419, 1320. 1H NMR (400 MHz, DMSO-

D.K. Barange et al. / Tetrahedron 67 (2011) 2870e2877
2877
Verotta, L.; Lovaglio, E.; Vidari, G.; Finzi, P. V.; Neri, M. G.; Raimondi, A.; Para-
pini, S.; Taramelli, D.; Riva, A.; Bombardelli, E. Phytochemistry 2004, 65,
2867e2879; (c) Garazd, M. M.; Garazd, Y. L.; Khilya, V. P. Khim. Prir. Soedin.
2003, 39, 47e82; (d) Guilet, D.; Helesbeux, J.-J.; Seraphin, D.; Sevenet, T.; Ri-
chomme, P.; Bruneton, J. J. Nat. Prod. 2001, 64, 563e568; (e) Patil, A. D.; Freyer,
A. J.; Eggleston, D. S.; Haltiwanger, R. C.; Bean, M. F.; Taylor, P. B.; Caranfa, M. J.;
Breen, A. L.; Bartus, H. R.; Johnson, R. K.; Hertzberg, R. P.; Westley, J. W. J. Med.
Chem. 1993, 36, 4131e4138; (f) O’Reilly, R. A. N. Engl. J. Med. 1976, 295, 354e357.
8. (a) Butenschon, I.; Moller, K.; Hansel, W. J. Med. Chem. 2001, 44, 1249e1256; (b)
Cahalan, M. D.; Chandy, K. G. Curr. Opin. Biotechnol. 1997, 8, 749e756; (c)
Slaughter, R. S.; Garcia, M. L.; Kaczorowski, G. J. Curr. Pharm. Des. 1996, 2,
610e623.
9. For the syntheis of Angular furoquinolinone: (a) Venkataraman, S.; Barange, D.
K.; Pal, M. Tetrahedron Lett. 2006, 47, 7317e7322; (b) Fayol, A.; Zhu, J. Angew.
Chem., Int. Ed. 2002, 41, 3633e3635; (c) Bar, G.; Parsons, A. F.; Thomas, C. B.
Tetrahedron 2001, 57, 4719e4728; (d) Pirrung, M. C.; Blume, F. Org. Lett. 1999, 64,
3642e3649.
d6)
d 10.62 (s, C]NeOH, (Z) isomer, 1H), 10.32 (s, C]NeOH, (E)
isomer, 1H), 7.94e7.91 (m, (E) isomer, 1H), 7.88e7.83 (m, (E) isomer
and (Z) isomer, 2H), 7.81e7.78 (m, (E) isomer and (Z) isomer, 2H),
7.77e7.73 (m, (E) isomer and (Z) isomer, 2H), 7.64 (d, J¼8.6 Hz, (E)
isomer 4H), 7.53e7.56 (m, (E) isomer and (Z) isomer, 2H), 7.44e7.34
(m, (E) isomer, 2H), 5.58 (s, (E) isomer, 1H), 5.40 (s, (Z) isomer, 1H),
3.58 (s, (Z) isomer, 3H), 3.53 (s, (E) isomer, 3H). 13C NMR (100 MHz,
DMSO-d6) d 165.3, 158.6, 158.0, 157.8, 140.6, 133.8, 133.0, 132.3 (2C),
127.9, 127.7, 127.5, 126.7, 126.5, 126.3, 126.0, 122.7, 122.5, 115.7, 111.9,
110.3, 48.7, 46.4, 28.9. MS (EI): (m/z) (relative intensity) 356 (Mþ, 5),
340 (100), 327 (55), 312 (45), 250 (17). HRMS (EI): calcd for
C22H16N2O3 (M)þ 356.1155, found 356.1170.
10. (a) Tu, Z.; Raju, B. R.; Liou, T.-R.; Kavala, V.; Kuo, C.-W.; Jang, Y.; Shih, Y.-H.; Yao,
C.-F. Tetrahedron 2009, 65, 2436e2442; (b) Gao, S.; Tu, Z.; Kuo, C.-W.; Liu, J.-T.;
Chu, C.-M.; Yao, C.-F. Org. Biomol. Chem. 2006, 4, 2851e2857; (c) Lin, C.; Hsu, J.;
Sastry, M. N. V.; Fang, H.; Tu, Z.; Liu, J.-T.; Yao, C.-F. Tetrahedron 2005, 61,
11751e11757; (d) Jang, Y.-J.; Yan, M.-C.; Lin, Y.-F.; Yao, C.-F. J. Org. Chem. 2004,
69, 3961e3963; (e) Yan, M.-C.; Tu, Z.; Lin, C.; Ko, S.; Hsu, J.; Yao, C.-F. J. Org.
Chem. 2004, 69, 1565e1570; (f) Jang, Y.-J.; Lin, W.-W.; Shih, Y.-K.; Liu, J.-T.;
Hwang, M.-H.; Yao, C.-F. Tetrahedron 2003, 59, 4979e4992; (g) Jang, Y.-J.; Shih,
Y.-K.; Liu, J.-Y.; Kuo, W.-Y.; Yao, C.-F. Chem.dEur. J. 2003, 9, 2123e2128; (h) Yan,
M.-C.; Tu, Z.; Lin, C.; Yao, C.-F. Tetrahedron Lett. 2002, 43, 7991e7994; (i) Liu, J.-
Y.; Liu., J.-T.; Yao, C.-F. Tetrahedron Lett. 2001, 42, 3613e3615; (j) Chu, C.-M.; Liu,
J.-T.; Lin, W.-W.; Yao, C.-F. J. Chem. Soc., Perkin Trans. 11999, 47e52; (k) Yao, C.-F.;
Chu, C.-M.; Liu, J.-T. J. Org. Chem. 1998, 63, 719e722.
Acknowledgements
We wish to express our sincere gratitude to the National Science
Council of the Republic of China and National Taiwan Normal
University (99T3030-2 and 99-D) for providing financial support
for this work. DKB is grateful to MOFA for a Taiwan Scholarship.
Supplementary data
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.02.062.
11. (a) Barange, D. K.; Raju, B. R.; Kavala, V.; Kuo, C.-W.; Tu, Y.-C.; Yao, C.-F. Tetra-
hedron 2010, 66, 3754e3760; (b) Barange, D. K.; Kavala, V.; Kuo, C.-W.; Tseng, C.;
Tu, Y.-C.; Yao, C.-F. Tetrahedron Lett. 2009, 50, 5116e5119.
References and notes
12. For the recent publications on C3-alkylation of 4-hydroxycoumarin: (a) Mog-
haddam, F. M.; Mirjafary, Z.; Saeidian, H.; Taheri, S.; Soltanzadeh, B. Tetrahedron
2010, 66, 3678e3681; (b) Yang, H.-M.; Li, L.; Jiang, K.-Z.; Jiang, J.-X.; Lai, G.-Q.;
Xu, K.-Z. Tetrahedron 2010, 60, 9708e9713; (c) Theerthagiri, P.; Lalitha, A. Tet-
rahedron Lett. 2010, 51, 5454e5458; (d) Grigg, R.; Whitney, S.; Sridharan, V.;
Keep, A.; Derrick, A. Tetrahedron 2009, 65, 7468e7473; (e) Lin, X.; Dai, X.; Mao,
Z.; Wang, Y. Tetrahedron 2009, 65, 9233e9237; (f) Khoshkholgh, M. J.; Lotfi, M.;
Balalaie, S.; Rominger, F. Tetrahedron 2009, 65, 4228e4234; (g) Reddy, C. H.;
Srikanth, B.; Rao, N. N.; Shin, D.-S. Tetrahedron 2009, 64, 11666e11672.
13. (a) Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Tetrahedron 2007, 64, 11636e11643;
(b) Xie, J.-W.; Yue, L.; Chen, W.; Du, W.; Zhu, J.; Deng, J.-G.; Chen, Y.-C. Org. Lett.
2007, 9, 413e415; (c) Zhang, L.; Meng, T.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72,
7279e7286; (d) Chen, Y.-S.; Kuo, P.-U.; Shie, T.-L.; Yang, D.-Y. Tetrahedron 2006,
62, 9410e9416; (e) Dittmer, D. C.; Li, Q.; Avilov, D. V. J. Org. Chem. 2005, 70,
4682e4686; (f) Chen, D. U.; Kuo, P. Y.; Yang, D. Y. Bioorg. Med. Chem. Lett. 2005,
15, 2665e2668; (g) Grigg, R.; Nurnabi, M.; Rahul, M.; Sarkar, A. Tetrahedron
2004, 59, 3359e3373; (h) Halland, N.; Hansen, T.; Jørgensen, K. A. Angew. Chem.,
Int. Ed. 2003, 42, 4955e4957; (i) Cravotto, G.; Nano, G. M.; Palmisano, G.; Ta-
gliapietra, S. Synthesis 2003, 8, 1286e1291.
1. (a) Meciarova, M.; Toma, S.; Magdolen, P. Ultrason. Sonochem. 2003, 10,
265e270; (b) Practical Sonochemistry. Power Ultrasound: Uses and Applications;
Mason, T. J., Peters, D., Eds.; Horwood Publishing Ltd: London, UK, 2002; (c) Del
Campo, F. J.; Maisonhaute, E.; Compton, R. G.; Marken, F.; Aldaz, A. J. Electroanal.
Chem. 2001, 506, 170e177; (d) Synthetic Organic Sonochemistry; Luche, J.-L., Ed.;
Plenum: New York, NY, 1998; (e) Mason, T. J. Chem. Soc. Rev. 1997, 26, 433e451;
(f) Suslick, K. S.; Casadonte, D. J.; Green, M. L. H.; Thompson, M. E. Ultrasonics
1987, 25, 56e59.
2. (a) Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2010, 51, 4479e4481; (b) Scondo,
A.; Dumarcay-Charbonnier, F.; Barth, D.; Marsura, A. Tetrahedron Lett. 2009, 50,
5582e5584; (c) Luzzio, F. A.; Chen, J. J. Org. Chem. 2008, 73, 5621e5624; (d) Li,
J.-T.; Zhai, X.-L.; Lin, Z.-P.; Zhang, X.-H. Lett. Org. Chem. 2008, 5, 579e582; (e)
Cintas, P.; Cravotto, G. Chem. Soc. Rev. 2006, 35, 180e196 and references cited
therein.
3. (a) Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629e639; (b)
€
Lindstrom, U. M. Organic Reactions in Water: Principles, Strategies and Applica-
tions; Blackwell: New York, NY, 2007; 41; 629; (c) Pirrung, M. C. Chem.dEur. J.
2006, 12, 1312e1317; (d) Li, C.-J. Chem. Rev. 2005, 105, 3095e3166; (e)
14. For the syntheis of furoquinolinone: (a) Bhoga, U.; Mali, R. S.; Adapa, S. R.
Tetrahedron Lett. 2004, 45, 9483e9485 and references cited therein; (b) Raja-
manickam, P.; Shanmugam, P. Indian J. Chem. 1987, 26B, 910e913; (c) Kano, S.;
Shibuya, S.; Ebata, T. Heterocycles 1981, 15, 1011e1015; (d) Narasimhan, N. S.;
Mali, R. S. Tetrahedron 1974, 30, 4153e4157.
€
Lindstrom, U. M. Chem. Rev. 2002, 102, 2751e2772; (f) Shu, K.; Kei, M. Acc. Chem.
Res. 2002, 35, 209e217; (g) Li, C. J.; Chang, T. H. Organic Reactions in Aqueous
Media; Wiley: New York, NY, 1997; 7950; (h) Breslow, R. Acc. Chem. Res. 1991,
24, 159e164.
4. (a) Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2005, 44, 3275e3279; (b) Klijin, J. E.; Engberts, J. B. F. N.
Nature 2005, 435, 746e747.
5. (a) Yamamoto, Y.; Kurazono, M. Bioorg. Med. Chem. Lett. 2007, 17, 1626e1628;
(b) Xia, Y.; Yang, Z.-Y.; Xia, P.; Hackl, T.; Hamel, E.;Mauger, A.; Wu, J.-H.; Lee, K.-H. J.
Med. Chem. 2001, 44, 3932e3936; (c) Naser-Hijazi, B.; Stolze, B.; Zanker, K. S.
Second Proceedings of the International Society of Coumarin Investigators; Springer:
Berlin,1994; (d) Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural Coumarins:
Occurrence, Chemistry, and Biochemistry; Wiley: New York, NY, 1982.
6. (a) Michael, J. P. Nat. Prod. Rep. 2004, 21, 650e668; (b) Michael, J. P. Nat. Prod.
Rep. 2003, 20, 476e493.
15. Ishikawa, T.; Miyahara, T.; Asakura, M.; Higuchi, S.; Miyauchi, Y.; Saito, S. Org.
Lett. 2005, 7, 1211e1214.
16. (a) Habib, P. M.; Kavala, V.; Kuo, C.-W.; Yao, C.-F. Tetrahedron Lett. 2008, 49,
7005e7008; (b) Habib, P. M.; Kavala, V.; Raju, B. R.; Kuo, C.-W.; Huang, W. C.;
Yao, C.-F. Eur. J. Org. Chem. 2009, 4503e4514.
17. (a) Ansell, G. B.; Moore, D. W.; Neilsen, A. T. J. Chem. Soc. B 1971, 2376e2382; (b)
€
€
ꢀ
Nagy, P. I.; Kokosi, J.; Gergely, A.; Racz, A. J. Phys. Chem. A 2003, 107, 7861e7868;
(c) Dominianni, S. J.; Chaney, M. O.; Jones, N. D. Tetrahedron Lett. 1970, 54,
4735e4736.
18. CCDC number of the 12a and 15a are 793324 and 793322 respectively. These
data can be obtained free of charge from Cambridge Crystallographic Data
Center via www.ccdc.cam.ac.uk/datarequest/cif.
19. We are thankful the reviewer for his valuable suggestion regarding the
mechanism.
7. For biological activities of coumarin: (a) Argotte-Ramos, R.; Ramırez-Avila, G.;
Rodrıguez-Gutierrez, M. d. C.; Ovilla-Munoz, M.; Lanz-Mendoza, H.; Rodrıguez,
M. H.; Gonzalez-Cortazar, M.; Alvarez, L. J. Nat. Prod. 2006, 69, 1442e1444; (b)