Simple and efficient method for three-component synthesis of spirooxindoles in aqueous and solvent-free media

Article abstract of DOI:10.1080/00397911003587507

A clean, simple, one-pot, three-component synthesis of some important spirooxindole derivatives in the presence of tetrabutylammonium bromide (TBAB) was carried out under green and environmentally benign conditions.

Full text of DOI:10.1080/00397911003587507

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Simple and Efficient Method for Three-
Component Synthesis of Spirooxindoles
in Aqueous and Solvent-Free Media
a
a
Akbar Mobinikhaledi , Naser Foroughifar & Mohammad Ali Bodaghi
a
Fard
a
Faculty of Sciences, Department of Chemistry, Arak University,
Arak, Iran
Version of record first published: 13 Jan 2011.
To cite this article: Akbar Mobinikhaledi, Naser Foroughifar & Mohammad Ali Bodaghi Fard (2011):
Simple and Efficient Method for Three-Component Synthesis of Spirooxindoles in Aqueous and
Solvent-Free Media, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:3, 441-450
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1
Synthetic Communications , 41: 441–450, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003587507
SIMPLE AND EFFICIENT METHOD
FOR THREE-COMPONENT SYNTHESIS OF
SPIROOXINDOLES IN AQUEOUS AND
SOLVENT-FREE MEDIA
Akbar Mobinikhaledi, Naser Foroughifar, and
Mohammad Ali Bodaghi Fard
Faculty of Sciences, Department of Chemistry, Arak University, Arak, Iran
A clean, simple, one-pot, three-component synthesis of some important spirooxindole deri-
vatives in the presence of tetrabutylammonium bromide (TBAB) was carried out under
green and environmentally benign conditions.
Keywords: Aqueous; multicomponent; spirooxindole; TBAB
INTRODUCTION
Multicomponent reactions (MCRs) have attracted the attention of synthetic
organic chemists for building highly functionalized organic molecules and pharma-
[
1,2]
cologically important heterocyclic compounds.
in a wide variety of pharmacologically and biologically active compounds.
Furthermore, it has been reported that sharing the indole 3-carbon atom in the
The indole framework is common
[
3]
[
4,5]
formation of spiroindoline derivatives highly enhances the biological activity.
The spirooxindole system is the core structure of some pharmacological agents
and natural alkaloids.
Organic reactions in water without using harmful organic solvents being
focused on today, especially in our environmentally conscious society. To the
best of our knowledge, there have been a few reports about the synthesis of
[6–9]
[
10–13]
[14–18]
spirooxindole derivatives in an aqueous medium. As a consequence of our interest
in the aqueous organic syntheses and our continued work on the synthesis of hetero-
[19–21]
cyclic compounds,
guided by the observation that the presence of two or more
different heterocyclic moieties in a single molecule often enhances the biological pro-
file remarkably, we investigated a three-component reaction of isatin, molononitrile
or ethyl cyanoacetate, and CH- acids (1,3-dicarbonyl compounds) to afford a series
of spirooxindole derivatives in water or solvent-free conditions mediated by the
TBAB (tetrabutyl ammonium bromide). In recent years, TBAB has been used as
[
22–25]
an extremely useful catalyst in various organic transformations.
TBAB is also
Received September 14, 2009.
Address correspondence to Akbar Mobinikhaledi, Faculty of Sciences, Department of Chemistry,
Arak University, Arak 38156879, Iran. E-mail: akbar_mobini@yahoo.com
4
41

442
A. MOBINIKHALEDI, N. FOROUGHIFAR, AND M. A. B. FARD
an inexpensive, available catalyst and has inherent properties such as environmental
compatibility, greater selectivity, operational simplicity, noncorrosive nature, and
ease of reusability.
RESULTS AND DISCUSSION
In our initial study, the evaluation of various conditions was studied for
the synthesis of spirooxindole derivatives. After some preliminary experiments, it
was found that a mixture of isatin, malononitrile, and dimedone in water in the pres-
ence of a catalytic amount of TBAB could afford 2-amino-5-oxo-7,7-dimethyl
0
0
0
0
spiro[(4H)-5,6,7,8-tetrahydrochromene-4,3 -(3 H)-indol]-(1 H)-2 -one-carbonitrile in
excellent yield (4a, Scheme 1). The procedure was simple and easy to operate. We
have also investigated the synthesis of our target compounds under solvent-free neat
conditions. Interestingly, the reaction was carried out for 40 min, and 90% of pure
compound was obtained.
This method works with a wide variety of substrates. A series of substituted
isatin and different CH- acids were used in this reaction (Schemes 1 and 2).
Additionally, the reaction with malononitrile or ethyl cyanoacetate also pro-
ceeded smoothly. Thereafter, different substituted spirooxindole derivatives were
prepared successfully in water and under solvent-free neat conditions. Some of these
derivatives are novel. The results are listed in Table 1. In this study, the products
1
13
were characterized by melting point, infrared (IR), H NMR, and C NMR (some
selected products) spectral data; as well as by elemental analyses.
Scheme 1. Synthesis of spirooxindoles from 1,3-dicarbonyl compounds promoted by TBAB.
Scheme 2. TBAB-catalyzed synthesis of spirooxindoles from CH- acids.

SYNTHESIS OF SPIROOXINDOLES
443
Table 1. Synthesis of spirooxindole derivatives in aqueous and solvent-free media
Method A
Method B
Time (min) Yield (%)
a
a
Entry
R
R
1
X
Y
Product Time (min) Yield (%)
1
2
3
4
5
6
7
8
9
H
H
H
CN
—
—
—
—
—
O
4a
4b
30
40
25
45
45
35
40
40
40
60
50
75
60
60
55
75
60
90
90
90
92
89
93
87
88
90
89
88
90
87
91
88
86
83
85
82
85
80
81
80
40
45
40
45
50
50
50
—
60
60
60
75
75
75
90
90
90
100
100
100
90
83
90
83
85
84
85
5-Br
H
CN
CN
CH
CH
H
3
4c
4d
H
2
Ph CN
H
CO
CN
2
Et
Et
4e
6a
H
H
H
H
CO
CN
2
O
6b
6c
b
H
H
S
—
88
82
83
79
80
78
81
80
85
78
77
78
H
H
CN
CN
—
—
—
—
—
—
—
—
—
—
—
—
8a
8b
1
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
8
9
0
5-Br
H
H
CH
CH
H
3
CN
Ph CN
8c
8d
H
2
H
CO
CO
2
Et
Et
8e
8f
H
CH
H
3
2
H
CN
CN
10a
10b
10c
10d
10e
10f
5-Br
H
H
CH
CH
H
3
CN
Ph CN
H
2
H
5-Br
CO
CO
2
Et
Et
H
2
a
b
Isolated yields.
A complex product was obtained.
The proposed mechanism for the synthesis of spirooxindol derivative 8a is
described in Scheme 3. In this process, the isatin 1 first condenses with malononitrile
to afford isatylidene malononitrile derivative 12 in the presence of TBAB. This step
2
is regarded as a fast Knoevenagel condensation. Then, 12 is attacked via Michael
addition of CH- acids such as 4-hydroxy coumarine 7 to give the intermediate 13 fol-
lowed by the cycloaddition of hydroxyl group to the cyano moiety to form the
desired product 8a (Scheme 3).
CONCLUSION
In conclusion, we have described a simple and efficient three-component reac-
tion involving isatin, activated methylene reagent, and CH- acids (1,3-dicarbonyl
compounds) for the synthesis of a series of spirooxindole derivatives, some of which
are novel, in water and solvent-free conditions. Further merits of this method are
its generality, short reaction times, good yields, simple operation, environmental
compatibility, and easy workup.
EXPERIMENTAL
Melting points were obtained in open capillaries on an Electrothermal 5000
digital apparatus and are not corrected. IR spectra were recorded on a Galaxy series
Fourier transform FT–IR 5000 spectrometer. NMR spectra were recorded on a

444
A. MOBINIKHALEDI, N. FOROUGHIFAR, AND M. A. B. FARD
Scheme 3. The plausible mechanism for the synthesis of spirooxindoles.
Brucker-300-MHz spectrometer in dimethylsulfoxide (DMSO-d ) with tetramethylsi-
6
lane (TMS) as an internal standard. Microanalyses were performed on an elemental
analyzer (Elemental, Vario EL III). Progress of the reactions was followed by
thin-layer chromatography (TLC) using n-hexane=EtOAc (3:1 v=v) as an eluent.
Typical Procedure for the Synthesis of Spirooxindols
Method A (in water). In a typical reaction, a mixture of isatin (1 mmol), mal-
ononitrile, or ethyl cyanoacetate (1 mmol): dimedone or other CH- acids (1 mmol):
and TBAB (10 mol%) in refluxing water (5 ml) was stirred for an appropriate time.
After completion, monitored by TLC, the reaction mixture was allowed to cool to
room temperature. The solid was filtered off, washed with water (2 ꢀ 10 ml), and
recrystallized from EtOH=H O (3:1) to afford the product.
2
Method B (solvent-free). In this procedure, the components as mentioned
ꢁ
previously were mixed thoroughly and heated in an oil bath maintained at 100 C
for the appropriate time. The reaction mixture was then cooled to room temperature.
The mixture was washed with water (2 ꢀ 10 ml) and recrystallized from EtOH=H O
2
(3:1) to afford the pure product.

SYNTHESIS OF SPIROOXINDOLES
445
Physical and Spectroscopic Data for Selected Compounds
2
-Amino-5-oxo-7,7-dimethyl-spiro[(4H)-5,6,7,8-tetrahydrochromene-
ꢁ
4
,3’-(3’H)-indol]-(1’H)-2’-one-carbonitrile (4a). Mp 296–298 C; IR (KBr) (nmax):
3
6
311, 3144, 2960, 2193, 1724, 1682, 1656, 1604, 1471, 1348, 1222, 1055, 764,
ꢂ1
1
15 cm ; H NMR (300 MHz, DMSO-d ): dH: 10.43 (s, 1H, NH), 7.26 (br s, 2H,
6
NH ), 7.18 (t, 1H, J ¼ 7.6 Hz, ArH), 7.01 (d, 1H, J ¼ 6.7 Hz, ArH), 6.92 (t, 1H,
2
J ¼ 6.8 Hz, ArH), 6.82 (d, 1 Hz, J ¼ 7.6 Hz, ArH), 2.52–2.65 (m, 2H, CH ), 2.21
2
(
d, 1H, J ¼ 16.0 Hz, CH), 2.12 (d, 1H, J ¼ 16.0 Hz, CH), 1.06 (s, 3H, CH ), 1.02
3
1
3
(s, 3H, CH ) ppm; C NMR (75 MHz, DMSO-d ): dC 195.4, 178.5, 164.3, 159.2,
3
6
1
42.4, 134.8, 128.6, 123.4, 122.1, 117.8, 111.2, 109.7, 57.9, 50.4, 47.2, 32.4, 28.0,
7.4, 26.7 ppm. Anal. calcd. for C H N O : C, 68.05; H, 5.11; N, 12.53%. Found:
2
C, 68.48; H, 5.27; N, 12.71%.
1
9
17
3
3
2-Amino-5-oxo-7,7-dimethyl-spiro[(4H)-5,6,7,8-tetrahydrochromene-
ꢁ
,3’-(3’H)-5’-bromo-indol]-(1’H)-2’-one-carbonitrile (4b). Mp >300 C; IR
4
(
1
KBr) (nmax): 3367, 3288, 3159, 2958, 2195, 1728, 1680, 1655, 1602, 1475, 1350,
222, 1057, 810, 619 cm ; H NMR (300 MHz, DMSO-d ): dH 10.59 (s, 1H,
6
ꢂ1
1
NH), 7.37 (s, 2H, NH ), 7.24–7.34 (m, 2H, ArH), 6.79 (d, 1H, J ¼ 8.1 Hz, ArH),
2
2
CH ) ppm; Anal. calcd. for C H BrN O : C, 55.09; H, 3.89; N, 10.14%. Found:
.53–2.66 (m, 2H, CH ), 2.12–2.24 (m, 2H, CH ), 1.05 (s, 3H, CH ), 1.02 (s, 3H,
2 2 3
3
19 16
3
3
C, 55.31; H, 3.98; N, 10.36%.
2-Amino-5-oxo-7,7-dimethyl-spiro[(4H)-5,6,7,8-tetrahydrochromene-4,3’-
3’H)-1’-methyl-indol]-(1’H)-2’-one-carbonitrile (4c). Mp 258–260 C (254–
ꢁ
(
ꢁ
[18]
2
1
7
56 C);
IR (KBr) (n ): 3375, 3286, 3144, 2960, 2193, 1714, 1666, 1602, 1467,
1
max
ꢂ1
350, 1221, 740 cm ; H NMR (300 MHz, DMSO-d ): dH 7.34 (s, 2H, NH ),
.26–7.31 (m, 2H, ArH), 6.98–7.09 (m, 3H, ArH), 3.16 (s, 3H, CH ), 2.53–2.65
3
6
2
(
m, 2H, CH ), 2.19 (d, 1H, J ¼ 16.0 Hz, CH), 2.11 (d, 1H, J ¼ 16.0 Hz, CH), 1.05
2
1
3
(s, 3H, CH ), 1.02 (s, 3H, CH ) ppm; C NMR (75 MHz, DMSO-d ): dC 195.3,
3 3 6
1
5
5
77.0, 164.7, 159.3, 144.01, 134.0, 128.8, 123.2, 122.9, 117.0, 111.1, 108.6, 57.4,
0.3, 46.9, 32.4, 28.0, 27.5, 26.8 ppm. Anal. calcd. for C H N O : C, 68.75; H,
.48; N, 12.03%. Found: C, 69.17; H, 5.47; N, 12.05%.
2
0
19
3
3
2-Amino-5-oxo-7,7-dimethyl-spiro[(4H)-5,6,7,8-tetrahydrochromene-4,3’-
3’H)-1’-benzyl-indol]-(1’H)-2’-one-carbonitrile (4d). Mp 271–273 C (269–
ꢁ
(
ꢁ
[18]
2
71 C);
IR (KBr) (nmax): 3385, 3321, 3205, 2962, 2197, 1716, 1660, 1601, 1467,
ꢂ1
1
1
352, 1219, 1051, 750 cm ; H NMR (300 MHz, DMSO-d ): dH 7.52 (d, 2H,
6
J ¼ 7.1 Hz, ArH), 7.38 (s, 2H, NH ), 7.26–7.34 (m, 2H, ArH), 7.11–7.19 (m, 2H,
2
ArH), 6.99 (t, 1H, J ¼ 7.4 Hz, ArH), 6.72 (d, 1H, J ¼ 7.8 Hz, ArH), 4.97 (d, 1H,
J ¼ 16.2 Hz, CH Ph), 4.90 (d, 1H, J ¼ 16.2 Hz, CH Ph), 2.57–2.70 (m, 2H, CH ),
2
2
2
2
1
.25 (d, 1H, J ¼ 16.0 Hz, CH), 2.16 (d, 1H, J ¼ 16.0 Hz, CH), 1.08 (s, 3H, CH )
3
.04 (s, 3H, CH ) ppm. Anal. calcd. for C H N O : C, 73.39; H, 5.45; N, 9.88%.
3
26 23
3
3
Found: C, 73.67; H, 5.58; N, 9.93%.
Ethyl 2-amino-5-oxo-7,7-dimethyl-spiro[(4H)-5,6,7,8-tetrahydrochromene-
ꢁ
4
3
,3’-(3’H)-indol]-(1’H)-2’-one-carboxylate (4e). Mp 232–235 C; IR (KBr) (n ):
max
ꢂ1
1
371, 3180, 3113, 2960, 1714, 1689, 1650, 1601, 1741, 1348, 1226, 754 cm ; H
NMR (300 MHz, DMSO-d ): dH 10.18 (s, 1H, NH), 7.90 (s, 2H, NH ), 7.10
6
2

446
A. MOBINIKHALEDI, N. FOROUGHIFAR, AND M. A. B. FARD
(
6
2
t, 1H, J ¼ 7.5 Hz, ArH), 6.97 (d, 1H, J ¼ 7.2 Hz, ArH), 6.87 (t, 1H, J ¼ 7.2 Hz, ArH),
.72 (d, 1H, J ¼ 7.5 Hz, ArH), 3.64 (q, 2H, J ¼ 7.8 Hz, CH ), 2.45–2.58 (m, 2H, CH ),
2 3 3
2
2
.06–2.36 (m, 2H, CH ), 1.07 (s, 3H, CH ), 1.03 (s, 3H, CH ), 0.99 (t, 3H, J ¼ 7.8 Hz,
CH ) ppm. Anal. calcd. for C H N O : C, 65.96; H, 5.80; N, 7.33%. Found: C,
3
21 22
2
5
6
6.19; H, 5.89; N, 7.47%.
2
-Amino-5,7-dioxo-spiro[(3’H)-indol-3’,4,4(H)-5,6,7,8-tetrahydropyrano
ꢁ
(
2
1
2,3-d)pyrimidine]-(1’H)-2’-one-3-carbonitrile
75–276 C);
531, 1392, 1330, 1111, 754 cm ; H NMR (300 MHz, DMSO-d ): dH 12.32 (br
(6a). Mp
273–275 C
(lit.
ꢁ
[18]
IR (KBr) (nmax): 3404, 3337, 3306, 3146, 2202, 1724,1672, 1620,
ꢂ1
1
6
s, 1H, NH), 11.15 (s, 1H, NH), 10.51 (s, 1H, NH), 7.40 (s, 2H, NH ), 7.15–7.22
2
(
m, 2H, ArH), 6.94 (t, 1H, J ¼ 7.5 Hz, ArH), 6.82 (d, 1H, J ¼ 7.5 Hz, ArH) ppm.
Anal. calcd. for C H N O : C, 55.73; H, 2.81; N, 21.66%. Found: C, 55.37; H,
4
1
5
9
5
2
.85; N, 21.32%.
Ethyl 2-amino-5,7-dioxo-spiro[(3’H)-indol-3’,4,4(H)-5,6,7,8-tetrahydro-
ꢁ
pyrano(2,3-d)pyrimidine]-(1’H)-2’-one-3-carboxylate (6b). Mp 207–209 C. IR
(
1
1
KBr) (nmax): 3618, 3495, 3321, 3202, 2980, 1720, 1695, 1682, 1616, 1471, 1327,
ꢂ1
m
1
253, 1118, 752 c ; H NMR (300 MHz, DMSO-d ): dH 12.20 (br s, 1H, NH),
6
1.00 (s, 1H, NH), 10.27 (s, 1H, NH), 7.98 (s, 2H, NH ), 7.09 (t, 1H, J ¼ 7.5 Hz,
2
ArH), 6.97 (d, 1H, J ¼ 7.0 Hz, ArH), 6.80 (t, 1H, J ¼ 7.0 Hz, ArH), 6.70 (d, 1H,
J ¼ 7.5 Hz, ArH), 3.37 (q, 2H, J ¼ 7.0 Hz, CH ), 0.80 (t, 3H, J ¼ 7.0 Hz, CH )
2
3
1
3
ppm; C NMR (75 MHz, DMSO-d ): dC 179.7, 167.9, 161.6, 159.0, 152.6, 149.5,
6
1
44.4, 135.7, 127.8, 123.2, 121.1, 108.6, 89.6, 76.6, 59.5, 46.6, 13.4 ppm. Anal. calcd.
for C H N O : C, 55.14; H, 3.81; N, 15.13%. Found: C, 55.02; H, 3.85; N, 15.25%.
1
7
14
4
6
2
pyrano(2,3-d)pyrimidine]-(1’H)-2’-one-3-carbonitrile (6c). Mp 243–245 C (lit.
-Amino-5-oxo-7-thioxo-spiro[(3’H)-indol-3’,4,4(H)-5,6,7,8-tetrahydro-
ꢁ
ꢁ
[18]
2
1
1
2
38–242 C);
IR (KBr) (nmax): 3520, 3427, 3317, 3159, 2202, 1693, 1656, 1616,
ꢂ1
1
570, 1400, 1342, 1132, 767 cm ; H NMR (300 MHz, DMSO-d ): dH 13.7 (br s,
6
H, NH), 12.55 (s, 1H, NH), 10.58 (s, 1H, NH), 7.46 (s, 2H, NH ), 7.14–7.31 (m,
H, ArH), 6.94 (t, 1H, J ¼ 7.5 Hz, ArH), 6.82 (d, 1H, J ¼ 7.6 Hz, ArH) ppm. Anal.
2
calcd. for C H N O S: C, 53.09; H, 2.67; N, 20.64; S, 9.45%. Found: C, 53.22;
9
15
5
3
H, 2.72; N, 20.51; S, 9.68%.
2
-Amino-5-oxo-spiro[(3’H)-indol-3’,4,4(H)-pyrano(2,3-c)chromen]-(1’H)-
[18]
ꢁ
ꢁ
2
3
7
’-one-3-carbonitrile (8a). Mp 293–295 C (lit. 292–294 C);
IR (KBr) (nmax):
358, 3298, 3198, 3043, 2206, 1712, 1674, 1602, 1471, 1357, 1219, 1082, 976,
ꢂ1
1
38 cm ; H NMR (300 MHz, DMSO-d ): dH: 10.72 (s, 1H, NH), 7.98 (d, 1H,
6
J ¼ 6.8 Hz, ArH), 7.87 (t, 1H, J ¼ 6.9 Hz, ArH), 7.71 (s, 2H, NH ), 7.5 (m, 2H,
2
ArH), 7.24 (d, 2H, J ¼ 6.2 Hz, ArH), 6.97 (t, 1H, J ¼ 7.5, ArH), 6.89 (d, 1H,
1
3
J ¼ 7.8 Hz, ArH) ppm; C NMR (75 MHz, DMSO-d ): dC 177.6, 158.9, 158.7,
6
1
1
3
55.5, 152.5, 142.6, 134.1, 133.5, 129.4, 125.5, 124.6, 123.1, 122.5, 117.4, 117.1,
12.9, 109.9, 101.8, 57.4, 48.1 ppm. Anal. calcd. for C H N O : C, 67.23; H,
.10; N, 11.76%. Found: C, 67.05; H, 3.23; N, 11.90%.
2
0
11
3
4
2
-Amino-5-oxo-spiro[(3’H)-5’-bromo-indol-3’,4,4(H)-pyrano(2,3-c)chromen]-
ꢁ
(
2
1’H)-2’-one-3-carbonitrile (8b). Mp > 300 C. IR (KBr) (n ): 3323, 3246, 3205,
max
ꢂ1
1
200, 1739, 1710, 1670, 1606 1473, 1359, 1221, 1085, 763 cm ; H NMR (300 MHz,

SYNTHESIS OF SPIROOXINDOLES
447
DMSO-d ): dH: 10.88 (s, 1H, NH), 7.97 (d, 1H, J ¼ 7.8 Hz, ArH), 7.78 (s, 2H, NH ),
6
2
7
.72–7.89 (m, 1H, ArH), 7.52–7.60 (m, 3H, ArH), 7.42 (d, 1H, J ¼ 7.3 Hz, ArH), 6.86
20 10 3 4
(d, 1H, J ¼ 8.2 Hz, ArH) ppm. Anal. calcd. for C H BrN O : C, 55.07; H, 2.31; N,
9
.63%. Found: C, 55.39; H, 2.43; N, 9.65%.
2
-Amino-5-oxo-spiro[(3’H)-1’-methyl-indol-3’,4,4(H)-pyrano(2,3-c)chromen]-
[18]
ꢁ
ꢁ
(
1’H)-2’-one-3-carbonitrile (8c). Mp 283–285 C (lit. 287–288 C);
IR (KBr)
(
7
(
7
nmax): 3599, 3470, 3288, 3169, 2210, 1710, 1676, 1606, 1471, 1356, 1099, 966,
ꢂ1
1
58 cm ; H NMR (300 MHz, DMSO-d ): dH 7.98 (d, 1H, J ¼ 7.9 Hz, ArH), 7.80
6
m, 3H, NH and ArH), 7.52–7.61 (m, 2H, ArH), 7.31–7.39 (m, 2H, ArH),
2
1
3
.03–7.12 (m, 2H, ArH), 3.24 (s, 3H, N-CH ) ppm; C NMR (75 MHz, DMSO-d6):
3
dC 176.1, 159.0, 158.7, 155.6, 152.5, 144.0, 134.2, 132.6, 129.5, 125.5, 124.3, 123.2,
23.1, 117.2, 117.1, 112.9, 108.9, 101.7, 57.0, 47.6, 27.0 ppm. Anal. calcd. for
C H N O : C, 67.92; H, 3.53; N, 11.32%. Found: C, 68.12; H, 3.71; N, 11.38%.
1
2
1
13
3
4
2-Amino-5-oxo-spiro[(3’H)-1’-benzyl-indol-3’,4,4(H)-pyrano(2,3-c)chromen]-
1’H)-2’-one-3-carbonitrile (8d). Mp 282–283 C (lit. 277–279 C) ; IR (KBr)
ꢁ
ꢁ
[18]
(
(
7
nmax): 3408, 3340, 3190, 3061, 2198, 1709, 1670, 1608, 1465, 1354, 1167, 964,
ꢂ1
1
54 cm ; H NMR (300 MHz, DMSO-d ): dH 7.99 (d, 1H, J ¼ 7.9 Hz, ArH), 7.82
6
(s, 2H, NH ), 7.79–7.85 (m, 1H, ArH), 7.50–7.62 (m, 4H, ArH), 7.22–7.38 (m, 5H,
2
ArH), 7.03 (t, 1H, J ¼ 7.4 Hz, ArH), 6.84 (d, 1H, J ¼ 7.8 Hz, ArH), 5.05 (d, 1H,
J ¼ 16.0 Hz, CH Ph), 4.97 (d, 1H, J ¼ 16.0 Hz, CH Ph) ppm. Anal. calcd. for
2
2
C H N O : C, 72.48; H, 3.83; N, 9.39%. Found: C, 72.77; H, 3.65; N, 9.42%.
4
2
7
17
3
Ethyl 2-amino-5-oxo-spiro[(3’H)-indol-3’,4,4(H)-pyrano(2,3-c)chromen]-
[17]
ꢁ
ꢁ
(
1’H)-2’-one-3-carboxylate (8e). Mp 214–215 C (lit. 210 C); IR (KBr) (nmax):
3
7
8
477, 3385, 3277, 3144, 3082, 1720, 1687, 1650, 1614, 1489, 1354, 1276, 1107, 1022,
ꢂ1 1
58 cm ; H NMR (300 MHz, DMSO-d ): dH 10.46 (s, 1H, NH), 8.18 (s, 2H, NH ),
6
2
.05 (d, 1H, J ¼ 7.9 Hz, ArH), 7.77 (t, 1H, J ¼ 8.4 Hz, ArH), 7.585 (t, 1H, J ¼ 7.6,
ArH), 7.48 (d, 1H, J ¼ 8.4 Hz, ArH), 7.15 (t, 1H, J ¼ 7.6 Hz, ArH), 7.05 (d, 1H,
J ¼ 7.3 Hz, ArH), 6.83 (t, 1H, J ¼ 7.6 Hz, ArH), 6.77 (d, 1H, J ¼ 7.6 Hz, ArH),
3
C H N O : C, 65.34; H, 3.99; N, 6.93%. Found: C, 65.73; H, 4.08; N, 6.85%.
.80 (q, 2H, J ¼ 7.1 Hz, CH ), 0.86 (t, 3H, J ¼ 7.1 Hz, CH ) ppm. Anal. calcd. for
22 16 2 6
2
3
Ethyl 2-amino-5-oxo-spiro[(3’H)-1’-methyl-indol-3’,4,4(H)-pyrano(2,3-c)
[17]
ꢁ
ꢁ
chromen]-(1’H)-2’-one-3-carboxylate (8f). Mp 253–255 C (lit. 244 C);
IR
(
1
KBr) (nmax): 3367, 3281, 3209, 2982, 1730, 1685, 1662, 1610, 1491, 1346, 1278,
103, 1022, 754 cm ; H NMR (300 MHz, DMSO-d ): dH 8.22 (s, 2H, NH ),
6 2
ꢂ1
1
8
.07 (d, 1H, J ¼ 7.8 Hz, ArH), 7.46–7.63 (m, 3H, ArH), 7.26 (t, 1H, J ¼ 7.6 Hz,
ArH), 7.12 (d, 1H, J ¼ 7 Hz, ArH), 6.90–6.98 (m, 2H, ArH), 3.75 (q, 2H, J ¼ 7.1 Hz,
Hz, CH ), 3.20 (s, 2H, N-CH ), 0.79 (t, 3H, J ¼ 7.1 Hz, CH ) ppm. Anal. calcd. for
2
3
3
C H N O : C, 66.02; H, 4.34; N, 6.70%. Found: C, 66.48; H, 4.51; N, 6.77%.
2
2
3
18
6
2
-Amino-5,10-dioxo-spiro[(3’H)-indol-3’,4,4(H)-benzo(g)chromen]-(1’H)-
ꢁ
2
2
’-one-3-carbonitrile (10a). Mp 250 C (dec.). IR (KBr) (nmax): 3447, 3346, 3067,
ꢂ1
1
206, 1732, 1668, 1593, 1469, 1411, 1342, 1201, 983, 754, 719 cm ; H NMR
(
7
300 MHz, DMSO-d ): dH 10.74 (s, 1H, NH), 8.11 (d, 1H, J ¼ 6.8 Hz, ArH),
6
.83–7.93 (m, 3H, ArH), 7.63 (br s, 2H, NH ), 7.21–7.27 (m, 2H, ArH), 6.90–6.98
2

448
A. MOBINIKHALEDI, N. FOROUGHIFAR, AND M. A. B. FARD
(m, 2H, ArH) ppm. Anal. calcd. for C H N O : C, 68.29; H, 3.00; N, 11.38%.
Found: C, 68.87; H, 3.11; N, 11.57%.
21 11 3 4
2
-Amino-5,10-dioxo-spiro[(3’H)-5’-bromo-indol-3’,4,4(H)-benzo(g)chromen]-
ꢁ
(
3
1’H)-2’-one-3-carbonitrile (10b). Mp > 300 C. IR (KBr) (nmax): 3456, 3379,
ꢂ1
1
171, 2218, 1741, 1674, 1595, 1473, 1336, 1205, 721 cm ; H NMR (300 MHz,
DMSO-d ): dH 10.88 (s, 1H, NH), 8.12 (dd, 1H, J ¼ 5.7, 2.6 Hz, ArH), 7.86–7.91
6
(
m, 3H, ArH), 7.72 (s, 2H, NH ), 7.56 (d, 1H, J ¼ 2.1 Hz, ArH), 7.42 (dd, 1H,
2
J ¼ 8.2, 2.1 Hz, ArH), 6.88 (d, 1H, J ¼ 8.2 Hz, ArH) ppm. Anal. calcd. for
C H BrN O : C, 56.27; H, 2.25; N, 9.37%. Found: C, 56.43; H, 2.36; N, 9.29%.
3
2
1
10
4
2
-Amino-5,10-dioxo-spiro[(3’H)-1’-methyl-indol-3’,4,4(H)-benzo(g)chromen]-
ꢁ
(
3
1’H)-2’-one-3-carbonitrile (10c). Mp 280–282 C; IR (KBr) (nmax): 3460, 3350,
ꢂ1
1
163, 2200, 1722, 1668, 1591, 1467, 1340, 1203, 763 cm ; H NMR (300 MHz,
DMSO-d ): dH: 8.11 (d, 1H, J ¼ 7.5 Hz, ArH), 7.81–7.90 (m, 3H, ArH), 7.68 (s,
6
2
1
1
1
H, NH ), 7.34 (d, 2H, J ¼ 8.3 Hz, ArH), 7.14 (d, 1H, J ¼ 7.6 Hz, ArH), 7.03 (t,
3 6
2
1
3
H, J ¼ 7.5 Hz, ArH), 3.28 (s, 3H, CH ) ppm; C NMR (75 MHz, DMSO-d ): dC
82.2, 176.7, 176.5, 159.1, 150.9, 143.6, 135.2, 134.9, 134.0, 130.9, 130.7, 129.5,
26.7, 126.4, 124.4, 123.1, 119.6, 117.3, 109.0, 56.9, 48.0, 27.0 ppm. Anal. calcd.
for C H N O : C, 68.93; H, 3.42; N, 10.96%. Found: C, 68.47; H, 3.59; N, 11.17%.
2
2
13
3
4
2
-Amino-5,10-dioxo-spiro[(3’H)-1’-benzyl-indol-3’,4,4(H)-benzo(g)chromen]-
ꢁ
(
3
1’H)-2’-one-3-carbonitrile (10d). Mp 192–195 C. IR (KBr) (nmax): 3431, 3323,
ꢂ1
1
211, 2197, 1718, 1664, 1563, 1465, 1334, 1205, 752 cm ; H NMR (300 MHz,
DMSO-d ): dH 10.76 (s, 1H, NH), 8.10 (d, 1H, J ¼ 7.2 Hz, ArH), 7.73 (s, 2H,
6
NH ), 7.85–7.90 (m, 3H, ArH), 7.57 (d, 1H, J ¼ 7.5 Hz, ArH), 7.24–7.40 (m, 5H,
2
ArH), 7.01 (t, 1H, J ¼ 7.8 Hz, ArH), 6.87 (d, 1H, J ¼ 7.8 Hz, ArH), 5.11 (d, 1H,
J ¼ 16.0 Hz, CH Ph), 4.97 (d, 1H, J ¼ 16.0 Hz, CH Ph) ppm. Anal. calcd. for
2
2
C H N O : C, 73.20; H, 3.73; N, 9.15%. Found: C, 73.67.; H, 3.88; N, 9.23%.
2
8
17
3
4
Ethyl 2-amino-5,10-dioxo-spiro[(3’H)-indol-3’,4,4(H)-benzo(g)chromen]-
ꢁ
(
1’H)-2’-one-3-carboxylate (10e). Mp 270 C (dec.); IR (KBr) (nmax): 3445,
ꢂ1
3
404, 3306, 2984, 1734, 1680, 1654, 1614, 1508, 1352, 1271, 1211, 1072, 721 cm
;
1
H NMR (300 MHz, DMSO-d ): dH 10.49 (s, 1H, NH), 8.20 (s, 2H, NH ), 8.06
6
2
(
d, 1H, J ¼ 8.4 Hz, ArH), 7.82–7.90 (m, 3H, ArH), 7.16 (t, 1H, J ¼ 7.6 Hz, ArH),
.10 (d, 1H, J ¼ 7.2 Hz, ArH), 6.79–6.83 (m, 2H, ArH), 3.79 (q, 2H, J ¼ 7.0 Hz,
CH ), 0.88 (t, 3H, J ¼ 7.0 Hz, CH ) ppm. Anal. calcd. for C H N O : C, 66.34;
7
2
3
23 16
2
6
H, 3.87; N, 6.73%. Found: C, 66.59; H, 4.01; N, 6.85%.
Ethyl 2-amino-5,10-dioxo-spiro[(3’H)-5’-bromo-indol-3’,4,4(H)-benzo(g)
ꢁ
chromen]-(1’H)-2’-one-3-carboxylate (10f). Mp 200–202 C. IR (KBr) (n ):
max
ꢂ1
3
396, 3144, 3068, 1714, 1682, 1645, 1614, 1469, 1303, 1271, 1213, 723, 530 cm
;
1
H NMR (300 MHz, DMSO-d ): dH 10.60 (s, 1H, NH), 8.02 (d, 1H, J ¼ 7.8 Hz,
6
ArH), 7.78–7.90 (m, 3H, NH and ArH), 7.41–7.48 (m, 2H, ArH), 6.86 (d, 1H,
2
J ¼ 8.2 Hz, ArH), 3.47 (q, 2H, J ¼ 7.0 Hz, CH ), 1.08 (t, 3H, J ¼ 7.0 Hz, CH )
2
3
ppm. Anal. calcd. for C H BrN O : C, 55.78; H, 3.05; N, 5.66%. Found: C,
2
3
15
2
6
5
5.47; H, 3.17; N, 5.59%.

SYNTHESIS OF SPIROOXINDOLES
449
ACKNOWLEDGMENT
We gratefully acknowledge the financial support from the Research Council of
Arak University.
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