Three-component synthesis of novel spirooxindole–furan derivatives using pyridinium salts

Article abstract of DOI:10.1016/j.crci.2016.07.001

A simple and efficient synthesis of novel spirooxindole–furan derivatives has been investigated by a modified version of the“interrupted” Feist–Bénary (IFB) reaction of isatin derivatives, 1,3-dicarbonyl compounds and N-phenacyl pyridinium salts in the presence of triethylamine. The reaction has been carried out under mild conditions in ethanol, and the products were obtained in good to moderate yields with a simple work-up procedure.

Full text of DOI:10.1016/j.crci.2016.07.001

C. R. Chimie xxx (2016) 1e6
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Full paper/M eꢀ moire
Three-component synthesis of novel spirooxindoleefuran
derivatives using pyridinium salts
*
Robabeh Baharfar , Sakineh Asghari, Farya Zaheri, Narges Shariati
Department of Chemistry, University of Mazandaran, P. O. Box 47415, Babolsar, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient synthesis of novel spirooxindoleefuran derivatives has been
investigated by a modified version of the“interrupted” FeisteBenary (IFB) reaction of isatin
derivatives, 1,3-dicarbonyl compounds and N-phenacyl pyridinium salts in the presence of
triethylamine. The reaction has been carried out under mild conditions in ethanol, and the
products were obtained in good to moderate yields with a simple work-up procedure.
Received 12 April 2016
Accepted 5 July 2016
Available online xxxx
ꢀ
Keywords:
©
2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Spirooxindole
Interrupted FeisteB eꢀ nary reaction
Isatin
1,3-dicarbonyl compounds
Pyridinium salts
1. Introduction
[14]. Also a new variant of this reaction has been reported,
including
a
-tosyloxyacetophenones as electrophiles
The oxindole framework has generated considerable
instead of
a
-haloketones. It has been shown that phenacyl
interest as a core constituent of many natural products and
biologically active molecules. In particular, spirooxindoles
are important heterocyclic compounds due to their various
biological and pharmacological properties. They are widely
used as antimicrobial [1], antitumor [2], and therapeutic
agents [3]. On the other hand, furan derivatives have
exhibited attractive biological activities, such as antitumor
bromides are poor reactants in the FeisteB eꢀ nary reaction,
but replacing Br with the tosyloxy group has led to good
results [15].
In order to expand the scope of the IFB reaction, and in
continuation of our previous works for the synthesis of
novel heterocyclic compounds [16e19], we report herein
an efficient procedure for the synthesis of new spiroox-
indoleefuran derivatives via the FeisteB eꢀ nary reaction of
[
4], antimicrobial [5,6], antispasmodic [7] and cytotoxic
properties [8]. Also, synthesis and pharmacological appli-
cation of various spirooxindoleefuran derivatives have
been reported [9e11].
N-phenacyl pyridinium salts as a reactive electrophile
with 1,3-dicarbonyl compounds and isatin derivatives
(Scheme 1).
The interrupted FeisteB eꢀ nary reaction (IFB) is a base-
catalyzed condensation of
dicarbonyl compounds, which form highly substituted
dihydrofuran derivatives [12,13]. Recently modified
FeisteB eꢀ nary
reaction for the synthesis of
bisspirooxindole-fused dihydrofurans has been reported
a-haloketones with 1,3-
2
. Results and discussion
a
In order to optimize the conditions, we studied the re-
action of N-phenacyl pyridinium bromide, dimedone and
isatin as the model reaction under various conditions
(Table 1). First, the reaction was examined in the presence
of different bases. As shown, using triethylamine gave
better yields than the other bases (Table 1, entry 5). Then,
the effect of various solvents and different temperatures
*
Corresponding author.
E-mail address: baharfar@umz.ac.ir (R. Baharfar).
http://dx.doi.org/10.1016/j.crci.2016.07.001
631-0748/© 2016 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.
1
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001

2
R. Baharfar et al. / C. R. Chimie xxx (2016) 1e6
Scheme 1. Preparation of novel spirooxindoleefuran derivatives.
Table 1
A plausible mechanism for the formation of products
a
Optimization of the reaction conditions.
4aek is given in Scheme 2. Initially, Knoevenagel conden-
sation between isatin derivatives and CH-acid of 1,3-
dicarbonyl compounds in the presence of triethylamine
affords adduct 5. Also the pyridinium salt is deprotonated
by triethylamine to give pyridinium ylide 6. In the second
step, a Michael addition of the pyridinium ylide 6 to adduct
ꢀ
Solvent Temp. ( C) Time (h) Yields (%)
Entry Base (eq)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
e
EtOH
EtOH
EtOH
EtOH
EtOH
50
50
50
50
50
50
50
50
50
50
50
50
24
15
15
18
10
24
24
10
15
12
14
24
24
10
e
K
2
CO
3
(1)
45
60
65
85
30
55
85
50
45
72
60
40
80
DBU (1)
DABCO (1)
NEt
NEt
NEt
NEt
NEt
NEt
NEt
NEt
NEt
NEt
3
3
3
3
3
3
3
3
3
3
(1)
5
produces dipolar intermediate 7. Finally, the attack of
(0.25) EtOH
enolate moiety in 7 to the electrophilic carbon bearing the
leaving pyridyl group leads to spirooxindole fused furan
derivative.
(0.5)
(2)
(1)
(1)
(1)
(1)
(1)
(1)
EtOH
EtOH
THF
0
1
2
3
4
H
2
O
DCM
e
3
. Experimental
EtOH
EtOH
25
Reflux
3.1. Materials and techniques
a
Reaction conditions: N-phenacyl pyridinium bromide (1 mmol),
All chemicals and reagents were purchased from Fluka
and Merck and used without further purification. Melting
points were measured with an Electrothermal 9100 appa-
ratus. NMR spectra were recorded with a Bruker DRX-400
dimedone (1 mmol), isatin (1 mmol), different conditions, stirring.
were examined. Using EtOH, the reaction afforded the
corresponding product with a good yield (85%) after 10 h at
1
ꢀ
AVANCE instrument (400.1 MHz for H, 100.6 MHz for
5
0 C (Table 1, entry 5). We also evaluated the amount of
13
3
C) with CDCl as solvent. Chemical shifts (d) are given in
triethylamine required for the reaction. It was found that
the use of 1 eq of NEt is sufficient to promote the reaction.
parts per million (ppm) relative to TMS, and coupling
constants (J) are reported in hertz (Hz). IR spectra were
recorded on an FT-IR Bruker vector 22 spectrometer. Mass
spectra were recorded on a Finnigan-Matt 8430 mass
spectrometer operating at an ionization potential of 70 eV.
3
In the presence of more than this amount of the base,
neither the yield nor the reaction time was improved.
After optimization of the model reaction, a variety of
spirooxindoleefuran derivatives were synthesized with the
three-component reaction of isatin derivatives with 1,3-
dicarbonyl compounds and pyridinium salts according to
Scheme 1. The target compounds were obtained in good
yields with high purity (Table 2). The structure of products
3.2. General procedure for the synthesis of compounds 4aek
N-Phenacyl pyridinium bromide derivatives were ob-
1
13
tained by the reaction of phenacyl bromide derivatives and
pyridine in acetonitrile medium. Triethylamine (1 mmol)
was added to a mixture of isatin (1 mmol) and 1,3-
dicarbonyl compounds (1 mmol) and N-phenacyl pyr-
was confirmed by IR, H and C NMR spectroscopy and
mass spectrometry.
The mass spectrum of 4a displayed the molecular ion
ꢁ
(
Mþ ) peak at m/z 387, which was consistent with the
1
ꢀ
idinium bromide in ethanol (5 ml) preheated at 50 C. The
product's structure. The H NMR spectrum of 4a in CDCl
3
ꢀ
reaction mixture was then stirred at 50 C for appropriate
exhibited two singlets at 1.15 and 1.22 ppm due to the two
time. After completion of the reaction, monitored by TLC on
SiO using EtOAc/hexane (1:1) as the eluent, the solvent
2
was removed under reduced pressure and the product was
obtained by recrystallization from diethyl ether.
methyl groups of dimedone, two doublets at 2.14 and
2
2
(
.31 ppm ( JHH ¼ 16.4 Hz), two doublets 2.65 and 2.68 ppm
2
J
HH ¼ 18.0 Hz) for diastereotopic protons of two CH
2
groups, and one singlet at 6.48 ppm for CH group of furan
ring. The aromatic protons appeared as one doublet at
3
6
6
.45 ppm ( JHH ¼ 7.6 Hz) and four multiplets at around
3.3. Physical and spectral data for compounds 4aek
3.3.1. 2-Benzoyl-6,6-dimethyl-6,7-dihydro-2H-spiro
.59e7.44 ppm. The proton of NH in oxindole moiety was
observed as one broad singlet at 8.10 ppm. The proton-
decoupled 13C NMR spectrum of 4a showed 22 distinct
resonances, in agreement with the proposed structure. The
spiro carbon displayed a signal at 58.9 ppm.
0
0
[benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4a)
ꢀ
White powder, mp: 275e277 C; yield (0.33 g, 85%); IR
ꢂ1
(KBr) (
n
max, cm ): 3430 (NH), 2939 (Csp
3
eH), 1725, 1696
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001

R. Baharfar et al. / C. R. Chimie xxx (2016) 1e6
3
Table 2
a
Preparation of spirooxindoleefuran derivatives.
ꢀ
Entry
1
R1
R2
R3
1,3-dicarbonyl compound
Product
Time (h)
10
Mp ( C)
Yield (%)
85
H
H
H
H
4a
275e277
188e190
2
H
CH
3
CH
2
4b
12
73
3
4
H
H
CH
H
2
CO
2
Et
H
H
4c
13
12
165e167
242e244
70
76
4d
5
6
7
8
9
Cl
Br
Cl
Cl
H
H
H
H
H
H
Cl
4e
4f
10
10
11
11
10
260e263
274e276
158e160
203e205
248e249
80
78
74
82
80
H
CH
2
CO
2
Et
4g
4h
4i
PhCH
H
2
1
0
H
H
H
H
H
4j
12
10
245e247
235e237
70
76
11
Br
4k
a
Reaction conditions: N-phenacyl pyridinium bromide derivatives (1 mmol), dimedone (1 mmol), isatin derivatives (1 mmol), triethylamine (1 mmol),
ꢀ
EtOH, 50 C, stirring.
0
and 1645 (3C]O), 1476 (C]C), 1257 (Csp
2
eO), 1065
3.3.2. 2-Benzoyl-1 -ethyl-6,6-dimethyl-6,7-dihydro-2H-spiro
eO); 1H NMR (400 MHz, CDCl
),
d
(ppm): 1.15 and
[benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4b)
0
0
(
1
Csp
.22 (2s, 6H, 2CH
AB-system, CH
AB-system, CH
3
3
H
2
ꢀ
3
), 2.14 and 2.31 (2d, 2H,
J
HH ¼ 16.4 Hz,
White powder, mp: 188e190 C; yield (0.30 g, 73%); IR
), 2.65 and 2.68 (2d, 2H, 2JHH ¼ 18.0 Hz,
(KBr) (
n
max, cm ): 2954 (Csp
ꢂ1
eH), 1709, 1644 and 1612
2
3
3
1
2
), 6.45 (d, 1H,
J
HH ¼ 7.6 Hz, CHOxindole),
(3C]O), 1223 (Csp
CDCl ), (ppm): 1.13 (s, 3H, CH
CH ), 1.20 (s, 3H, CH
), 2.08 and 2.28 (2d, 2H, JHH ¼ 16.4 Hz,
AB-system, CH
), 2.65 and 2.67 (2d, 2H, JHH ¼ 18.0 Hz, AB-
system, CH ), 3.49e3.77 (m, 2H, CH ), 6.46 (d, 1H,
HH ¼ 7.6 Hz, CHOxindole), 6.47 (s,1H, CHfuran), 6.88e6.90 (m,
2H, 2CHAr), 7.04e7.08 (m, 1H, CHAr), 7.19e7.23 (m, 2H,
2CHAr), 7.31e7.43 (m, 3H, 3CHAr); C NMR (100 MHz,
CDCl ), (ppm): 12.2, 27.7 and 29.5 (3CH ), 34.5 (CMe ),
35.2, 37.7 and 50.8 (3CH ), 58.6 (Cspiro), 91.4 (CHfuran), 108.0
2
eO), 1064 (Csp
3
eO); H NMR (400 MHz,
3
6
.48 (s, 1H, CHfuran), 6.86e6.87 (m, 2H, 2CHAr), 6.95e7.00
3
d
H
3
), 1.15 (t, 3H, JHH ¼ 7.2 Hz,
2
(
3
m, 1H, CHAr), 7.22e7.28 (m, 2H, 2CHAr), 7.40e7.44 (m, 3H,
3
3
13
2
CHAr), 8.10 (br s, 1H, NH); C NMR (100 MHz, CDCl
), 34.5 (CMe ), 37.7 and 50.8
), 58.9 (Cspiro), 91.4 (CHfuran), 109.8 (CHAr), 114.6 (Cq),
22.8 and 124.7 (2CHAr), 126.5 (Cq), 127.5 and 128.5
3
),
d
C
2
(
(
ppm): 27.7 and 29.5 (2CH
2CH
3
2
2
2
3
2
J
1
13
(
(
4CHAr), 129.1 and 133.7 (2CHAr), 134.5, 139.8 and 177.4
3Cq), 178.2 (COamide), 192.2 and 192.3 (2COketone); MS,
3
d
C
3
2
þ
ꢁ
m/z: 387 (M ).
2
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001

4
R. Baharfar et al. / C. R. Chimie xxx (2016) 1e6
Scheme 2. Proposed mechanism for the preparation of spirooxindoleefuran derivatives.
(
CHAr), 114.7 (Cq), 122.7 and 124.6 (2CHAr), 126.4 (Cq), 127.4
1641 (3C]O), 1225 (Csp
(400 MHz, CDCl ), (ppm): 2.07e2.27 (m, 2H, CH
2.29e2.41 (m, 2H, CH ), 2.71e2.91 (m, 2H, CH ), 6.45 (d, 1H,
2
eO), 1070 (Csp
3
eO); 1H NMR
),
and 128.4(4CHAr), 129.0 and 133.5 (2CHAr), 134.8, 141.8 and
1
MS, m/z: 415 (M ).
3
d
H
2
75.3 (3Cq), 177.6 (COamide), 191.9 and 192.5 (2COketone);
2
2
þ
ꢁ
3
J
HH ¼ 8.4 Hz, CHOxindole), 6.46 (s,1H, CHfuran), 6.86e6.88 (m,
2H, CHAr), 6.96e6.99 (m,1H, CHAr), 7.23e7.28 (m, 2H, 2CHAr),
0
13
3
.3.3. Ethyl 2-(2-benzoyl-6,6-dimethyl-2 ,4-dioxo-4,5,6,7-
7.39e7.44 (m, 3H, 3CHAr), 7.81 (br s, 1H, NH); C NMR
0
0
tetrahydro-2H-spiro[benzofuran-3,3 -indoline]-1 -yl)acetate
3 C 2
(100 MHz, CDCl ), d (ppm): 21.5, 24.1 and 36.5 (3CH ), 59.0
(
4c)
(Cspiro), 91.2 (CHfuran), 109.6 (CHAr), 116.0 (Cq), 122.8 and
124.9 (2CHAr), 126.5 (Cq), 127.5 and 128.5 (4CHAr), 129.1 and
133.7 (2CHAr), 134.6, 139.6 and 177.4 (3Cq), 179.2 (COamide),
ꢀ
White powder, mp: 165e167 C; yield (0.33 g, 70%); IR
KBr) (
642 and 1615 (4C]O), 1204 (Csp
ꢂ1
(
1
n
max, cm ): 3064 (Csp
2
eH), 2968 (Csp
eO), 1061 (Csp
(ppm): 1.16 and 1.20 (2s, 6H,
), 1.30 (t, 3H, JHH ¼ 7.2 Hz, CH ), 2.13 and 2.25 (2d, 2H,
), 2.64 and 2.70 (2d, 2H,
), 4.22e4.32 (m, 2H, CH ), 4.36
), 6.43 (d,
3
eH),1751,1707,
1
þ
ꢁ
2
2
eO);
H
192.3 and 192.7 (2COketone); MS, m/z: 359 (M ).
NMR (400 MHz, CDCl ),
3
d
H
3
0
2
CH
3
3
3.3.5. 2-Benzoyl-5 -chloro-6,6-dimethyl-6,7-dihydro-2H-spiro
2
0
0
JHH ¼ 16.4 Hz, AB-system, CH
2
[benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4e)
2JHH ¼ 18.0 Hz, AB-system, CH
White powder, mp: 260e263 C; yield (0.34 g, 80%); IR
ꢀ
2
2
2
ꢂ1
and 4.43 (2d, 2H, JHH ¼ 17.2 Hz, AB-system, NeCH
2
(KBr) (
n
max, cm ): 3291 (NH), 2958 (Csp
3
eH), 1727, 1696
3
1
1
(
2
d
H, JHH ¼ 7.6 Hz, CHOxindole), 6.45 (s, 1H, CHfuran), 6.83e6.91
and 1644 (3C]O), 1223 (Csp
(400 MHz, CDCl ), (ppm): 1.17 and 1.23 (2s, 6H, 2CH
2.17 and 2.29 (2d, 2H, JHH ¼ 16.4 Hz, AB-system, CH
2
eO), 1065 (Csp
3
eO); H NMR
),
), 2.63
), 6.39 (d,
m, 2H, 2CHAr), 7.01e7.04 (m, 1H, CHAr), 7.26e7.29 (m, 2H,
3
d
H
3
13
2
CHAr), 7.41e7.48 (m, 3H, 3CHAr); C NMR (100 MHz, CDCl
3
),
), 37.8, 42.0
), 90.7 (CHfuran),
2
2
C
(ppm): 14.1, 28.0 and 29.1 (3CH
3
), 34.5 (CMe
2
and 2.72 (2d, 2H, JHH ¼ 18.0 Hz, AB-system, CH
2
3
and 50.9 (3CH
1
1
1
2
), 58.6 (Cspiro), 61.7 (OCH
2
1H, JHH ¼ 8.4 Hz, CHOxindole), 6.46 (s, 1H, CHfuran), 6.85 (d,
4
3
08.1 (CHAr), 114.4 (Cq), 123.2 and 124.8 (2CHAr), 125.7 (Cq),
27.7 and 128.6 (4CHAr), 129.0 and 133.7 (2CHAr), 134.3 and
41.7 (2Cq), 167.1 (COester), 176.1 (Cq), 178.1 (COamide), 191.7
1H,
J
J
HH ¼ 2.0 Hz, CHAr), 6.97 (dd, 1H,
J
HH ¼ 8.4 Hz,
4
3
HH ¼ 2.0 Hz, CHAr), 7.28 (t, 2H,
J
HH ¼ 8.4 Hz, 2CHAr),
13
7.44e7.47 (m, 3H, 3CHAr), 7.93 (br s, 1H, NH); C NMR
(100 MHz, CDCl ), (ppm): 28.0 and 29.2 (2CH ), 34.5
CMe ), 37.7 and 50.8 (2CH ), 58.9 (Cspiro), 91.2 (CHfuran),
þ
ꢁ
and 192.0 (2COketone); MS, m/z: 473 (M ).
3
d
C
3
(
2
2
0
3
.3.4. 2-Benzoyl-6,7-dihydro-2H-spiro[benzofuran-3,3 -
110.6 (CHAr), 114.3 (Cq), 125.1 and 127.6 (4CHAr), 128.2 and
128.3 (2Cq), 128.7, 129.1 and 133.9 (3CHAr), 134.5, 138.3 and
176.9 (3Cq), 178.6 (COamide), 191.9 and 192.3 (2COketone);
0
indoline]-2 ,4(5H)-dione (4d)
White powder, mp: 242e244 C; yield (0.27 g, 76%); IR
(
ꢀ
ꢂ1
MS, m/z: 423 and 421 (M ꢁ).
þ
KBr) (
n
max, cm ): 3307 (NH), 2929 (Csp
3
eH),1724,1702 and
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001

R. Baharfar et al. / C. R. Chimie xxx (2016) 1e6
5
0
3
[
.3.6. 2-Benzoyl-5 -bromo-6,6-dimethyl-6,7-dihydro-2H-spiro
3.3.9. 2-(4-Chlorobenzoyl)-6,6-dimethyl-6,7-dihydro-2H-spiro
0
0
0
0
benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4f)
[benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4i)
ꢀ
ꢀ
White powder, mp: 274e276 C; yield (0.36 g, 78%); IR
White powder, mp: 248e249 C; yield (0.34 g, 80%); IR
ꢂ1
ꢂ1
(
KBr) (
n
max, cm ): 3300 (NH), 2954 (Csp
3
eH), 1728, 1696
(KBr) (
n
max, cm ): 3291 (NH), 2960 (Csp
3
eH), 1735, 1690
3
1
1
and 1648 (3C]O), 1220 (Csp
400 MHz, CDCl ), (ppm): 1.18 and 1.23 (2s, 6H, 2CH
.18 and 2.30 (2d, 2H, JHH ¼ 16.4 Hz, AB-system, CH
2
eO), 1065 (Csp
3
eO); H NMR
),
), 2.65
), 6.32 (d,
and 1639 (3C]O), 1224 (Csp
(400 MHz, CDCl ), (ppm): 1.15 and 1.22 (2s, 6H, 2CH
2.15 and 2.33 (2d, 2H, JHH ¼ 16.4 Hz, AB-system, CH
2
eO), 1062 (Csp
eO); H NMR
),
), 2.66
), 6.42 (s,
HH ¼ 8.0 Hz, CHOxindole),
6.83e6.86 (m, 2H, 2CHAr), 6.97e7.01 (m, 1H, CHAr), 7.22 (d,
(
2
3
d
H
3
3
d
H
3
2
2
2
2
2
2
and 2.71 (2d, 2H, JHH ¼ 18.0 Hz, AB-system, CH
2
and 2.68 (2d, 2H, JHH ¼ 14.4 Hz, AB-system, CH
2
3
3
1
H, JHH ¼ 8.4 Hz, CHOxindole), 6.46 (s, 1H, CHfuran), 6.98 (d,
1H, CHfuran), 6.49 (d, 1H,
J
4
3
1
H,
J
HH ¼ 2.0 Hz, CHAr), 7.10 (dd, 1H,
J
HH ¼ 8.4 Hz,
4
3
3
3
J
HH ¼ 2.0 Hz, CHAr), 7.28 (t, 2H,
J
HH ¼ 8.4 Hz, 2CHAr),
2H, JHH ¼ 8.8 Hz, 2CHAr), 7.36 (d, 2H, JHH ¼ 8.8 Hz, 2CHAr),
13
13
7
(
(
1
1
.43e7.47 (m, 3H, 3CHAr), 8.10 (br s, 1H, NH); C NMR
100 MHz, CDCl ), (ppm): 28.1 and 29.2 (2CH ), 34.6
CMe ), 37.7 and 50.8 (2CH ), 58.8 (Cspiro), 91.2 (CHfuran),
11.2 (CHAr), 114.2 and 115.3 (2Cq), 127.6 and 127.8 (4CHAr),
28.6 (Cq), 128.7, 132.0 and 133.9 (3CHAr), 134.5, 138.9 and
8.70 (br s, 1H, NH); C NMR (100 MHz, CDCl
3
),
d
C
(ppm):
),
3
d
C
3
27.7 and 29.4 (2CH
3
), 34.5 (CMe
2
), 37.7 and 50.8 (2CH
2
2
2
59.0 (Cspiro), 91.3 (CHfuran), 110.2 (CHAr), 114.6 (Cq), 122.8
and 124.6 (4CHAr), 126.4 (Cq), 128.8, 128.9 and 129.2
(3CHAr), 132.8, 140.0, 140.2 and 177.5 (4Cq), 178.3 (COamide),
1
76.8 (3Cq), 178.8 (COamide), 191.9 and 192.3 (2COketone);
MS, m/z: 467 and 465 (M ꢁ).
191.1 and 192.4 (2COketone); MS, m/z: 423 and 421 (M ꢁ).
þ
þ
3
.3.10. 6-Benzoyl-1,3-dimethyl-1H-spiro[furo [2,3-d]
0
0
0
0
3
4
.3.7. Ethyl 2-(2-benzoyl-5 -chloro-6,6-dimethyl-2 ,4-dioxo-
pyrimidine-5,3 -indoline]-2,2 ,4(3H,6H)-trione (4j)
0
0
ꢀ
,5,6,7-tetrahydro-2H-spiro[benzofuran-3,3 -indoline]-1 -yl)
White powder, mp: 245e247 C; yield (0.28 g, 70%); IR
ꢂ1
acetate (4g)
(KBr) (
n
max, cm ): 3430 (NH), 2925 (Csp
3
eH), 1709 and
ꢀ
1
White powder, mp: 158e160 C; yield (0.38 g, 74%); IR
1646 (2C]O), 1190 (Csp
(400 MHz, CDCl ), (ppm): 3.23 and 3.58 (2s, 6H,
2NeCH
2
eO), 1111 (Csp eO); H NMR
3
ꢂ1
(
KBr) (
n
max, cm ): 3034 (Csp
2
eH), 2925 (Csp
eO), 1069 (Csp eO); H NMR
(ppm): 1.18 and 1.21 (2s, 6H, 2CH ),
HH ¼ 7.2 Hz, CH ), 2.20 and 2.24 (2d, 2H,
), 2.63 and 2.72 (2d, 2H,
3
eH), 1725 and
3
d
H
1
3
1
(
645 (2C]O), 1215 (Csp
400 MHz, CDCl ),
.31 (t, 3H, 3
2
2
3
), 6.48 (d, 1H, JHH ¼ 7.6 Hz, CHOxindole), 6.60 (s, 1H,
3 4
3
d
H
3
CHfuran), 6.90 (td, 1H,
J
HH ¼ 7.6 Hz,
J
HH ¼ 0.8 Hz, CHAr),
3
4
1
J
3
6.94 (td, 1H, JHH ¼ 8.0 Hz, JHH ¼ 0.8 Hz, CHAr), 7.01 (td, 1H,
2
3
4
J
HH ¼ 13.2 Hz, AB-system, CH
2
J
HH ¼ 7.6 Hz, JHH ¼ 1.6 Hz, CHAr), 7.25e7.29 (m, 2H, 2CHAr),
2JHH ¼ 18.0 Hz, AB-system, CH
), 4.22e4.27 (m, 2H, CH
),
),
7.42e7.47 (m, 3H, 3CHAr), 7.97 (br s, 1H, NH); C NMR
(100 MHz, CDCl ), d (ppm): 27.9 and 30.1 (2CH ), 58.8
3 C 3
(Cspiro), 91.1 (CHfuran), 109.9 and 123.2 (2CHAr), 125.4 and
125.6 (2Cq), 127.5 and 128.7 (4CHAr), 129.6 and 134.1
(2CHAr), 139.7 (Cq), 148.0 (CHAr), 151.4 and 158.1 (2Cq),
163.2, 176.9 and 179.8 (3COamide), 190.6 (COketone); MS, m/z:
13
2
2
2
2
4
6
.31 and 4.46 (2d, 2H, JHH ¼ 17.6 Hz, AB-system, NeCH
3
.37 (d, 1H, JHH ¼ 8.4 Hz, CHOxindole), 6.44 (s, 1H, CHfuran),
4
3
6
.86 (d, 1H, JHH ¼ 2.0 Hz, CHAr), 7.01 (dd, 1H, JHH ¼ 8.4 Hz,
4
3
J
HH ¼ 2.4 Hz, CHAr), 7.28 (t, 2H,
J
HH ¼ 8.4 Hz, 2CHAr),
13
7
(
.48e7.52 (m, 3H, 3CHAr); C NMR (100 MHz, CDCl
ppm): 14.1, 28.3 and 28.9 (3CH ), 34.6 (CMe ), 37.8, 42.1
and 50.8 (3CH ), 58.1 (Cspiro), 61.9 (OCH ), 90.4 (CHfuran),
09.1 (CHAr), 114.0 (Cq), 125.2 and 127.8 (4CHAr), 128.3 (Cq),
28.8 and 129.0 (2CHAr), 133.5 (Cq), 133.9 (CHAr), 134.2 and
40.7 (2Cq), 166.9 (COester), 175.7 (Cq), 178.5 (COamide), 191.6
3 C
), d
þ
ꢁ
3
2
403 (M ).
2
2
1
1
1
3.3.11. 2-(4-Bromobenzoyl)-6,6-dimethyl-6,7-dihydro-2H-
spiro[benzofuran-3,3 -indoline]-2 ,4(5H)-dione (4k)
0
0
ꢀ
White powder, mp: 235e237 C; yield (0.35 g, 76%); IR
and 191.8 (2COketone); MS, m/z: 509 and 507 (M ꢁ).
þ
(KBr) (
n
max, cm ): 3290 (NH), 2958 (Csp
eO), 1066 (Csp
3 H
H NMR (400 MHz, CDCl ), d (ppm): 1.15 and 1.22 (2s, 6H,
ꢂ1
eH), 1723 and
3
1
650 (2C]O), 1475 (C]C), 1224 (Csp
2
3
eO);
0
0
1
3
.3.8. 2-Benzoyl-1 -benzyl-5 -chloro-6,6-dimethyl-6,7-
dihydro-2H-spiro[benzofuran-3,3 -indoline]-2 ,4(5H)-dione
0
0
2
2CH
CH
CH
3
), 2.14 and 2.32 (2d, 2H,
J
HH ¼ 16.4 Hz, AB-system,
(4h)
2
2
), 2.64 and 2.69 (2d, 2H, 2JHH ¼ 18.4 Hz, AB-system,
ꢀ
3
White powder, mp: 203e205 C; yield (0.42 g, 82%); IR
), 6.41 (s, 1H, CHfuran), 6.53 (d, 1H,
J
HH ¼ 8.0 Hz,
ꢂ1
(
KBr) (
n
max, cm ): 3090 (Csp
2
eH), 2959 (Csp
eO), 1074 (Csp eO); H NMR
(ppm): 1.18 and 1.24 (2s, 6H, 2CH
3
eH), 1713
CHOxindole), 6.85e6.91 (m, 2H, 2CHAr), 7.01e7.05 (m, 1H,
1
3
and 1644 (2C]O), 1229 (Csp
400 MHz, CDCl ),
.18 and 2.33 (2d, 2H,
2
2
CHAr), 7.28 (d, 2H,
J
HH ¼ 8.8 Hz, 2CHAr), 7.40 (d, 2H,
3
13
(
3
d
H
3
2
2
2
),
),
),
),
J
HH ¼ 8.8 Hz, 2CHAr), 7.85 (br s, 1H, NH); C NMR
2
2
2
4
6
6
J
J
HH ¼ 16.4 Hz, AB-system, CH
(100 MHz, CDCl
(CMe ), 37.7 and 50.8 (2CH
3
),
d
C
(ppm): 27.7 and 29.4 (2CH
3
), 34.5
2
.67 and 2.71 (2d, 2H,
HH ¼ 18.0 Hz, AB-system, CH
2
2
), 58.9 (Cspiro), 91.2 (CHfuran),
2
.28 and 5.18 (2d, 2H, JHH ¼ 16.0 Hz, AB-system, NeCH
109.8 (CHAr), 113.0 (Cq), 123.0 and 124.8 (4CHAr), 126.4 (Cq),
128.9, 129.0 and 129.3 (3CHAr), 131.9, 133.3, 139.6 and 177.2
(4Cq), 178.0 (COamide), 191.3 and 192.1 (2COketone); MS, m/z:
3
.12 (d, 1H, JHH ¼ 8.8 Hz, CHOxindole), 6.51 (s, 1H, CHfuran),
.88e6.90 (m, 2H, 2CHAr), 7.20e7.24 (m, 2H, 2CHAr),
þ
7
.29e7.39 (m, 7H, 7CHAr), 7.44e7.48 (m, 1H, CHAr);
467 and 465 (M ꢁ).
1
3
C NMR (100 MHz, CDCl
2CH ), 34.5 (CMe ), 37.8, 44.5 and 50.8 (3CH
spiro), 91.5 (CHfuran), 110.1 (CHAr), 114.3 (Cq), 124.9 and
3
),
d
C
(ppm): 28.0 and 29.3
(
(
3
2
2
), 58.6
4. Conclusion
C
1
26.9 (4CHAr), 127.5 and 127.7 (2CHAr), 127.8 and 128.4
In conclusion, we have demonstrated an efficient, clean
and step-wise economic procedure for the synthesis of
novel spirooxindoleefuran derivatives through a new
variant of the interrupted FeisteB eꢀ nary reaction using N-
(
2Cq), 128.5 and 128.9 (4CHAr), 129.0 and 133.7 (2CHAr),
1
34.5, 134.7, 140.5 and 175.7 (4Cq), 178.3 (COamide), 192.0
and 192.1 (2COketone); MS, m/z: 513 and 511 (M ꢁ).
þ
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001

6
R. Baharfar et al. / C. R. Chimie xxx (2016) 1e6
phenacyl pyridinium salts as electrophiles. The corre-
sponding products have been obtained in good yields
under very convenient conditions.
[3] C.V. Galliford, K.A. Scheidt, Angew. Chem. Int. Ed. 46 (2007) 8748.
[
[
[
[
[
[
4] S.M. Kupchan, M.A. Eakin, A.M. Thomas, J. Med. Chem. 111 (1971)
147.
5] M. Hofnung, V.M. Quillardet, E. Touati, Res. Microbiol. 153 (2002)
27.
6] M.W. Khan, M.J. Alam, M.A. Rashid, R. Chowdhury, Bioorg. Med.
Chem. 13 (2005) 4796.
7] J. Kobayashi, Y. Ohizumi, H. Nakamura, Tetrahedron Lett. 27 (1986)
1
4
Acknowledgements
This research was supported by the Research Council of
the University of Mazandaran, Iran.
2113.
8] M.M. Bandurraga, W. Fenical, S.F. Donovan, J. Clardy, J. Am. Chem.
Soc. 104 (1982) 6463.
9] Y. Zhang, Y. Lu, W. Tang, T. Lu, D. Du, Org. Biomol. Chem. 12 (2014)
3009.
Appendix A. Supplementary data
[
[
[
10] B. Yu, D.Q. Yu, H.M. Liu, Eur. J. Med. Chem. 97 (2015) 673.
11] M.M. Santos, Tetrahedron 70 (2014) 9735.
12] F. Feist, Ber. Dtsch. Chem. Ges. 35 (1902) 1537.
[13] E. B eꢀ nary, Ber. Dtsch. Chem. Ges. 44 (1911) 489.
Supplementary data related to this article can be found
at http://dx.doi.org/10.1016/j.crci.2016.07.001.
[
[
[
[
[
[
14] S. Ahadi, H.R. Khavasi, A. Bazgir, Chem. Eur. J. 19 (2013) 12553.
15] M.A. Calter, A. Korotkov, Org. Lett. 13 (2011) 6328.
16] R. Baharfar, N. Shariati, C. R. Chim. 17 (2014) 413.
17] R. Baharfar, N. Shariati, Turk. J. Chem. 39 (2015) 235.
18] R. Baharfar, R. Azimi, J. Chem. Sci. 127 (2015) 1389.
19] R. Baharfar, S. Asghari, S. Rassi, M. Mohseni, Res. Chem. Intermed. 41
References
[
[
1] G. Bhaskar, Y. Arun, C. Balachandran, C. Saikumar, P.T. Perumal, Eur.
J. Med. Chem. 51 (2012) 79.
2] X. Jiang, Y. Sun, J. Yao, Y. Cao, M. Kai, N. He, X. Zhang, Y. Wang,
R. Wang, Adv. Synth. Catal. 354 (2012) 917.
(2015) 6975.
Please cite this article in press as: R. Baharfar, et al., Three-component synthesis of novel spirooxindoleefuran derivatives using
pyridinium salts, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.07.001