Ammonium salt catalyzed multicomponent transformation: simple route to functionalized spirochromenes and spiroacridines

Article abstract of DOI:10.1016/j.tet.2009.08.070

The combination of isatin or acenaphthoquinone, an activated methylene reagent, and 1,3-dicarbonyl compounds in the presence of catalytic ammonium chloride was found to be a suitable and efficient method for the synthesis of the biologically important spirooxindoles.

Full text of DOI:10.1016/j.tet.2009.08.070

Tetrahedron 65 (2009) 9443–9447
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ammonium salt catalyzed multicomponent transformation: simple route
to functionalized spirochromenes and spiroacridines
*
Minoo Dabiri , Mahboobeh Bahramnejad, Mostafa Baghbanzadeh
Department of Chemistry, Faculty of Science, Shahid Beheshti University, G. C., Tehran 1983963113, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 March 2009
Received in revised form 9 August 2009
Accepted 28 August 2009
Available online 1 September 2009
The combination of isatin or acenaphthoquinone, an activated methylene reagent, and 1,3-dicarbonyl
compounds in the presence of catalytic ammonium chloride was found to be a suitable and efficient
method for the synthesis of the biologically important spirooxindoles.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent transformation
Spirooxindoles
Ammonium chloride
Water
Heterocycle
1. Introduction
H
N
H
N
Compounds with an indole moiety exhibit antibacterial and
antifungal activities.1 Furthermore, it has been reported that spi-
roindoline derivatives have highly enhanced biological activity.2–4
The spirooxindole system is the core structure of many pharma-
cological agents and natural alkaloids.5–9 For example, cytostatic
alkaloids as spirotryprostatins A, B, and pteropodine, and iso-
pteropodine have been shown to modulate the function of mus-
carinic serotonin receptors (Fig. 1).10
O
O
O
O
N
H
N
O
O
MeO
N
N
H
H
Spirotryprostatin A
Spirotryprostatin B
Isatin and its derivatives also have interesting biological proper-
ties andare widely used as precursorsfor many naturalproducts.11–15
On the basis of biological studies, the existence of two or more dif-
ferent heterocyclic moieties in a single molecule often enhances the
biocidal activity remarkably,16–18 and we intended the synthesis of
a series of spirooxindoles with fused chromenes through a three-
component reaction of isatin or acenaphthoquinone, malononitrile
or ethylcyanoacetate, and 1,3-dicarbonyl compounds in the presence
of catalytic ammonium chloride under aqueous conditions. Fused
chromenes have received considerable attention due to their wide
range of useful biological properties, which include spasmolitic, di-
uretic, anticoagulant, anticancer, and antianaphylactic activities.19–23
There are several reports on multicomponent entries to the
synthesis of spirooxindoles. Recently, Shanthi et al. reported
Me
Me
H
N
O
N
O
H
H
H
H
H
O
O
OMe
OMe
N
H
N
H
O
O
Pteropodine
Isopteropodine
Figure 1. Illustration of spirooxindole-containing compounds.
a three-component condensation of cyclic 1,3-diketones, isatin, and
malononitrile catalyzed by 20 mol % of InCl3.24 Spirooxindoles were
also prepared by electrochemical methods25 that suffer from
technical intricacy. This reaction was carried out in the presence of
the surfactant triethylbenzylammonium chloride (TEBA) in water
* Corresponding author.
E-mail address: m-dabiri@sbu.ac.ir (M. Dabiri).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.08.070

9444
M. Dabiri et al. / Tetrahedron 65 (2009) 9443–9447
medium.26 An important disadvantage of this approach was the
generation of mixtures of pyrans and unsaturated nitriles. Shesto-
palov et al. have described a three-component Et3N-catalyzed
procedure for the combinatorial synthesis of 2-amino-spiro pyrans
under simple conditions.27 Thus, we tried to utilize a more appro-
priate and more accessible acidic catalyst, NH4Cl, and water for
these transformations. This method is very expedient and would be
useful for the synthesis of different types of spirooxindoles.
Water plays an important role in the formation of the so-called
‘chemistry of life’. Its importance in chemistry has decreased in the
last century because of the introduction of organic solvents as more
convenient reaction media for the preparation of new organic
molecules. However, the demands of recent decades for sustainable
and ecologically friendlier procedures have again put water at the
frontier of organic chemistry.28,29 Breslow et al. used water in
combination with antihydrophobic additives as a mechanistic tool
for obtaining information about the nature and structure of tran-
sition states in transformations of molecules that are almost com-
pletely soluble in water.30,31 Mayr et al. have recently found an
important influence of water on the reactivity of organic molecules,
enabling alkylation of aromatic molecules with benzyl halides in
a water–acetonitrile mixture without the use of a Friedel–Crafts
catalyst.32,33 Very recently, Sharpless et al.34 reported the impor-
tant observation that some organic molecules can react on the
surface of water, and in some cases, a very strong enhancement in
reaction rates was noticed in comparison to reactions without the
solvent. The authors also suggested that water could be a useful
reaction medium for reactions where no acceleration of rate was
observed, especially in cases of exothermic reactions because of the
high heat capacity of water.
2. Results and discussion
In the course of our research and evaluation of different cata-
lysts and various solvent systems, we have found that ammonium
chloride has a unique capability to enhance the reaction rate in
aqueous medium. The results are summarized in Tables 1 and 2.
While, in some work, we observed that ammonium chloride and
other ammonium salts have been used as ammonia generator
Table 1
Solvent effects on the reaction of dimedone (1a), isatin (2a), and malononitrile (3a)
in the presence of 20 mol % ammonium chloride
Entry
Solventa
Time (min)
Yield of 4ab (%)
1
2
3
4
5
6
7
8
9
CH3OHc
C2H5OHc
CH3CNc
DMSOc
DMFc
480
360
600
600
600
600
600
600
10
60
75
20
Trace
Trace
Trace
Trace
Trace
92
CH3Clc
c
CH2Cl2
Solvent-freed
H2Od
a
Solvent (5 mL) was used.
Isolated yield.
The reaction was run under reflux condition.
The reaction was run at 80 ꢀC.
b
c
d
Table 2
Synthesis of spirooxindoles using various ammonium salt catalysts
Entry
Ammonium salt
Yield of 4aa (%)
1
2
3
4
5
6
NH4OAc
60
57
55
50
50
92
(NH4)2CO3
(NH4)2SO4
(NH4)2C2O4
(NH4)2S
In continuation of our investigations into the synthesis of novel
heterocyclic compounds under aqueous conditions,35–37 herein, we
wish to report an efficient and green protocol for the three-com-
ponent synthesis of some chromene derivatives at ambient tem-
perature in excellent yields (Schemes 1 and 2).
NH4Cl
a
Isolated yield based on 1,3-diketones.
R1
H2N
X
O
R1
O
O
R2
R2
R1
R1
NH4Cl (20 mol%)
+
O
NC
X
+
O
O
H2O, 80 °C,
10 min
N
O
N
H
H
4a-g
1a, b
3a, b
a R1=Me, R2=H, X=CN
2a, b
a R1=Me
b R1=H
a X=CN
b X=CO2Et
a R2=H
b R2=F
b R1=Me, R2=H, X=CO2Et
c R1=Me, R2=F, X=CN
d R1=Me, R2=F, X=CO2Et
e R1=H, R2=H, X=CN
f
R1=H, R2=H, X=CO2Et
g R1=H, R2=F, X=CO2Et
Scheme 1. Synthesis of spirooxindoles via three-component reaction.
R1
H2N
O
R1
O
O
O
X
O
NH4Cl (20 mol%)
O
R1
R1
+
+
NC
X
H2O, 80 °C,
10 min
O
3a, b
6a-d
1a, b
5
a X=CN
b X=CO2Et
a R1=Me, X=CN
a R1=Me
b R1=H
b R1=Me, X=CO2Et
c R1=H, X=CN
d R1=H, X=CO2Et
Scheme 2.

M. Dabiri et al. / Tetrahedron 65 (2009) 9443–9447
9445
agents,38–40 in the present exploration, the reaction of 1,3-dicar-
bonyl compounds (1a,b), isatin (2a,b), and activated methylene
reagents (3a,b) in a molar ratio of 1:1:1 in the presence of catalytic
ammonium chloride and water at 80 ꢀC for 10 min (Scheme 1)
furnished spirooxindoles in moderate yields (Table 3).
reaction and under similar conditions, not only a highly prolonged
time was required, but the products were different. The spectro-
scopic data of the products confirmed that these structures belong
to spiroacridine derivatives (Scheme 3, entries 12 and 13, Table 3).
3. Conclusion
Table 3
Synthesis of compounds 4, 6, 7, and 8 in water by the reaction of 1,3-diketones (1),
isatins (2) or acenaphthenequinone (5), and activated methylene compounds in the
presence of ammonium chloride
In conclusion, we have developed a clean and simple one-pot
three-component reaction for the synthesis of a series of spiro-
chromene derivatives catalyzed by ammonium chloride in water.
The utility of the described methodology in MCRs is highly prom-
ising as it allows for the combination of the synthetic virtues of the
conventional MCR strategy with the ecological benefits and con-
venience of the procedure.
Entry
Product
Time (min)
Yielda (%)
Mp (ꢀC)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
6a
6b
6c
6d
7
10
15
10
10
10
15
15
10
15
15
10
240
240
92
87
85
80
94
83
85
90
83
75
87
65
60
268–27026
257–258
270–273
240–242
251–25226
263–265
273–274
260–262
261–263
245–247
225–227
95–98
4. Experimental
4.1. General
9
10
11
12
13
Melting points were measured on an Electrothermal 9100 appa-
ratus. IR spectra were recorded on a FT-IR 10MB BOMEM spectrom-
eter. Mass spectra were documented on a FINNIGAN-MAT8430 mass
spectrometer operating at an ionization potential of 70 eV. The ele-
mental analysis was performed with an Elementar Analysensysteme
GmbH VarioEL CHNS mode. 1H and 13C NMR spectra were recorded
on a BRUKER DRX-300 AVANCE spectrometer at 300.13 and
75.47 MHz. NMR spectra were obtained in solutions of CDCl3 and
DMSO-d6 using TMS as internal standard. The chemicals used in this
work were purchased from Merck and Fluka Chemical Companies.
8
244–245
a
Isolated yield based on 1,3-diketones. The reactions were run at 80 ꢀC in the
presence of 20 mol % NH4Cl.
We examined this reaction in the absence and presence of
ammonium salts. It was observed that the reaction did not occur
without any catalyst. We also evaluated the amount of catalyst
required for this transformation. It was found that using 20 mol %
ammonium chloride in water is sufficient to push the reaction
forward. More amount of the catalyst did not increase the yield. In
order to evaluate the efficiency of this methodology, dimedone,
isatin, and malononitrile were further subjected to reaction using
20 mol % of a diverse type of ammonium salts such as ammonium
acetate, ammonium sulfate, ammonium carbonate, ammonium
oxalate, and ammonium sulfide as well as ammonium chloride
under identical conditions. As seen from Table 2, rate enhancement
of the reaction was observed when 20 mol % of ammonium chloride
was used. However, use of amount 20 mol % of other ammonium
salts led to lower yields (50–60%) after 10 min reaction time.
As shown in Table 3 it was found that this procedure works with
a wide variety of substrates. Two types of substituted isatins and 1,3-
cyclohexanediones were used in this reaction (Scheme 1). Also the
reaction with malononitrile or ethylcyanoacetate worked well. The
most probable mechanism of this reaction includes a fast Knoeve-
nagel condensation between isatin and CH-acidic cyanoacetic ester
derivatives in the presence of ammonium chloride in water in the
first step and a Michael addition of diketones to the unsaturated
nitrile, the product of Knovenagel condensation, in the second stage
and then the cycloaddition of the hydroxyl group to the cyano
moiety to form the desired product.26 To further expand the scope of
this approach, we examined one-pot reactions involving acenaph-
thoquinone (5), instead of isatin. Under these conditions, a variety of
desired spirochromenes were also produced in excellent yields
(Scheme 2, Table 3). On the other hand, when benzyl cyanide was
treated as a substitute for malononitrile or ethylcyanoacetate in this
4.2. Typical procedure for preparation of 2-amino-7,7-
dimethyl-20,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-4,30-
indoline]-3-carbonitrile (4a)
A mixture of isatin (1 mmol, 0.147 g), malononitrile (1 mmol,
0.066 g), 5,5-dimethyl-1,3-cyclohexanedione (1 mmol, 0.141 g),
and NH4Cl (0.2 mmol, 0.01 g) in H2O (5 mL) was stirred at 80 ꢀC for
10 min. Upon completion, monitored by TLC (n-hexane/ethyl ace-
tate:2/1), the reaction mixture was allowed to cool to room tem-
perature. The solid was filtered off and washed with water and cool
ethanol to give the desired products. The crude product was
recrystallized from EtOH to yield 2-amino-7,7-dimethyl-20,5-dioxo-
5,6,7,8-tetrahydrospiro[chromene-4,30-indoline]-3-carbonitrile 4a:
white solid (0.31 g, 92%). Mp 268–270 ꢀC, IR (KBr) (nmax, cmꢁ1):
3378, 3314, 2906, 2191, 1722, 1658, 1221. MS, m/z (%): 335 (Mþ, 50),
251 (100), 210 (25), 83 (23), 66 (23), 39 (35). 1H NMR (300.13 MHz,
DMSO-d6): dH (ppm) 0.99 (3H, s, CH3), 1.02 (3H, s, CH3), 2.08 (1H, d,
J¼16.1 Hz, CHAHB), 2.17 (1H, d, J¼15.9 Hz, CHAHB), 2.52 (2H, m, CH2),
6.76–7.15 (4H, m, ArH), 7.22 (2H, s, NH2), 10.40 (1H, s, NH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 27.46 (CH3), 28.06 (CH3), 32.40,
47.25 (CH2), 50.44 (CH2), 57.89, 109.69, 111.22, 117.81 (CN), 122.14,
123.47, 128.63, 134.87, 142.49, 159.22, 164.61, 178.50 (C]O amide),
195.37 (C]O). Anal. Calcd for C19H17N3O3: C, 68.05; H, 5.11; N,
12.53%. Found: C, 67.94; H, 5.23; N, 12.64%.
H
N
H
N
NH4Cl (20 mol%)
2a
1a
or
O
+
Ph
CN
+
O
O
H2O, 80 °C,
4 h
O
O
or
O
NH
5
65%
60%
7
8
Scheme 3.

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M. Dabiri et al. / Tetrahedron 65 (2009) 9443–9447
4.3. Ethyl-2-amino-7,7-dimethyl-20,5-dioxo-5,6,7,8-
281 (100), 253 (25), 55 (30), 39 (30). 1H NMR (300.13 MHz, DMSO-
d6): dH (ppm) 0.78 (3H, t, J¼7.1 Hz, CH3), 1.86 (2H, m, CH2), 2.15 (2H,
m, CH2), 2.63 (2H, m, CH2), 3.72 (2H, q, J¼6.1 Hz, CH2), 6.64–7.06
(4H, m, ArH), 7.85 (2H, s, NH2), 10.15 (1H, s, NH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 13.55 (CH3), 20.11 (CH2), 27.39
(CH2), 37.55 (CH2), 47.16, 59.29, 76.80,108.48,114.66, 120.98,122.89,
127.58, 136.55, 144.47, 159.44, 164.68, 168.11 (C]O, ester), 180.36
(C]O, amide), 195.29 (C]O). Anal. Calcd for C19H18N2O5: C, 64.40;
H, 5.12; N, 7.91%. Found: C, 64.08; H, 5.44; N, 8.23%.
tetrahydrospiro[chromene-4,30-indoline]-3-carboxylate (4b)
White solid (0.33 g, 87%). Mp 257–258 ꢀC, IR (KBr) (nmax, cmꢁ1):
3367, 3189, 2925, 1668, 1611, 1221. MS, m/z (%): 382(Mþ, 90), 309
(100), 281 (25), 83 (25), 41 (23). 1H NMR (300.13 MHz, DMSO-d6): dH
(ppm) 0.78 (3H, t, J¼6.57 Hz, CH3), 0.93 (3H, s, CH3),1.01 (3H, s, CH3),
2.00 (1H, d, J¼15.7 Hz, CHAHB), 2.14 (1H, d, J¼15.7 Hz, CHAHB), 2.55
(2H, m, CH2), 3.69 (2H, q, J¼5.2 Hz, CH2), 6.65–7.03 (4H, m, ArH),
7.86 (2H, s, NH2), 10.14 (1H, s, NH). 13C NMR (75.47 MHz, DMSO-d6):
dC (ppm) 13.55 (CH3), 27.12 (CH3), 28.25 (CH3), 32.0, 47.06 (CH2),
51.09 (CH2), 59.3 (CH2), 76.76, 108.58, 113.54, 120.99, 122.69, 127.63,
136.44, 144.49, 159.56, 162.86, 168.10 (C]O, ester), 180.26 (C]O,
amide), 195.11 (C]O). Anal. Calcd for C21H22N2O5: C, 65.96; H, 5.80;
N, 7.33%. Found: C, 65.72; H, 6.03; N, 7.57%.
4.8. Ethyl-2-amino-50-fluoro-20,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,30-indoline]-3-carboxylate (4g)
White solid (0.32 g, 85%). Mp 273–274 ꢀC, IR (KBr) (nmax, cmꢁ1):
3596, 3368, 3161, 1716, 1694, 1656, 1522, 1294. MS, m/z (%): 372
(Mþ, 65), 299 (100), 271 (25), 42 (45). 1H NMR (300.13 MHz, DMSO-
d6): dH (ppm) 0.8 (3H, t, J¼7.1 Hz, CH3), 1.87 (2H, m, CH2), 2.18 (2H,
m, CH2), 2.62 (2H, m, CH2), 3.71 (2H, q, J¼6.5 Hz, CH2), 6.63–6.88
(3H, m, ArH), 7.91 (2H, s, NH2), 10.19 (1H, s, NH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 13.57 (CH3), 20.04 (CH2), 27.43
(CH2), 37.5 (CH2), 47.71 (CH2), 59.36, 76.31,108.71,111,113.52,114.11,
138.31, 140.82, 156.60, 159.65, 165.06, 167.99 (C]O, ester), 180.34
(C]O, amide), 195.39 (C]O). Anal. Calcd for C19H17FN2O5: C, 61.29;
H, 4.60; N, 7.52%. Found: C, 61.12; H, 4.77; N, 7.69%.
4.4. 2-Amino-50-fluoro-7,7-dimethyl-20,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,30-indoline]-3-carbonitrile (4c)
Light pink solid (0.30 g, 85%). Mp 270–273 ꢀC, IR (KBr) (nmax
,
cmꢁ1): 3359, 3299, 3161, 2963, 2190,1726,1647,1345,1223. MS, m/z
(%): 353 (Mþ, 30), 269 (100), 227 (55), 42 (75). 1H NMR
(300.13 MHz, DMSO-d6): dH (ppm) 1.00 (3H, s, CH3), 1.04 (3H, s,
CH3), 2.07 (1H, d, J¼15.9 Hz, CHAHB), 2.15 (1H, d, J¼16.0 Hz, CHAHB),
2.51 (2H, m, CH2), 6.62–6.78 (3H, m, ArH), 7.70 (2H, s, NH2), 10.24
(1H, s, NH). 13C NMR (75.47 MHz, DMSO-d6): dC (ppm) 27.35 (CH3),
28.11 (CH3), 33.12, 47.35 (CH2), 51.2 (CH2), 59.12, 110.15, 112.28,
117.81 (CN), 123.09, 124.45, 129.58, 133.81, 144.52, 160.01, 167.52,
179.45 (C]O, amide),196.25 (C]O). Anal. Calcd for C19H16FN3O3: C,
64.58; H, 4.56; N, 11.89%. Found: C, 64.27; H, 4.87; N, 12.14%.
4.9. 20-Amino-70,70-dimethyl-2,50-dioxo-50,60,70,80-tetrahydro-
2H-spiro[acenaphthylene-1,40-chromene]-30-carbonitrile (6a)
Light yellow solid (0.33 g, 90%). Mp 260–262 ꢀC, IR (KBr) (nmax
,
cmꢁ1): 3369, 3186, 2953, 2192, 1718, 1667, 1598, 1215. MS, m/z (%):
370 (Mþ, 75), 286 (100), 259 (45), 83 (25), 39 (30). 1H NMR
(300.13 MHz, DMSO-d6): dH (ppm) 1.01 (3H, s, CH3), 1.03 (3H, s,
CH3), 2.05 (1H, d, J¼16.6 Hz, CHAHB), 2.12 (1H, d, J¼16.5 Hz, CHAHB),
2.62 (2H, m, CH2), 7.33 (2H, s, NH2), 7.37–8.28 (6H, m, ArH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 27.64 (CH3), 27.93 (CH3), 32.51,
50.16 (CH2), 51.42 (CH2), 58.47, 112.48, 117.97 (CN), 120.29, 121.87,
124.99, 128.93, 129.35,130.26, 131.91, 132.64, 140.98, 143.66, 159.23,
165.02, 195.77 (C]O), 204.05 (C]O). Anal. Calcd for C23H18N2O3: C,
74.58; H, 4.90; N, 7.56%. Found: C, 74.45; H, 5.15; N, 7.31%.
4.5. Ethyl-2-amino-50-fluoro-7,7-dimethyl-20,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,30-indoline]-3-carboxylate (4d)
White solid (0.32 g, 80%). Mp 240–242 ꢀC, IR (KBr) (nmax, cmꢁ1):
3396, 3350, 2953, 1705, 1688, 1665, 1488, 1170. MS, m/z (%): 400
(Mþ, 25), 327 (100), 299 (22), 83 (25), 41 (45). 1H NMR (300.13 MHz,
DMSO-d6): dH (ppm) 0.77 (3H, t, J¼6.5 Hz, CH3), 0.95 (3H, s, CH3),
1.00 (3H, s, CH3), 2.04 (1H, d, J¼16.6 Hz, CHAHB), 2.13 (1H, d,
J¼15.7 Hz, CHAHB), 2.55 (2H, m, CH2), 3.71 (2H, q, J¼6.5 Hz, CH2),
6.63–6.85 (3H, m, ArH), 7.91 (2H, s, NH2), 10.17 (1H, s, NH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 13.58 (CH3), 27.39 (CH3), 28.05
(CH3), 31.99, 47.61 (CH2), 51.07 (CH2), 59.36, 76.26, 108.85, 110.65,
113.39, 116.66, 138.23, 140.86, 159.62, 163.21, 167.98 (C]O, ester),
180.23 (C]O, amide), 195.22 (C]O). Anal. Calcd for C21H21FN2O5:
C, 62.99; H, 5.29; N, 7.00%. Found: C, 62.74; H, 5.54; N, 7.25%.
4.10. Ethyl-20-amino-70,70-dimethyl-2,50-dioxo-50,60,70,80-
tetrahydro-2H-spiro[acenaphthylene-1,40-chromene]-30-
carboxylate (6b)
White solid (0.35 g, 83%). Mp 261–263 ꢀC, IR (KBr) (nmax, cmꢁ1):
3380, 3269, 2953, 1718, 1687, 1519, 1222. MS, m/z (%): 418 (Mþþ1,
25), 344 (100), 271 (30), 83 (25). 1H NMR (300.13 MHz, DMSO-d6):
dH (ppm) 0.53 (3H, t, J¼7.0 Hz, CH3), 0.93 (3H, s, CH3), 1.01 (3H, s,
CH3), 1.92 (1H, d, J¼15.9 Hz, CHAHB), 2.07 (1H, d, J¼16.0 Hz, CHAHB),
2.62 (2H, m, CH2), 7.22–8.12 (6H, m, ArH), 7.94 (2H, s, NH). 13C NMR
(75.47 MHz, DMSO-d6): dC (ppm) 12.66 (CH3), 27.17 (CH3), 28.23
(CH3), 32.15, 50.48 (CH2), 51.16 (CH2), 58.86 (CH2), 77.67, 115.32,
119.46, 119.58, 124.23, 128.17, 128.68, 129.71, 129.89, 136.45, 141.09,
145.76, 159.85, 163.41, 167.91 (C]O, ester), 195.73 (C]O), 205.65
(C]O). Anal. Calcd for C25H23NO5: C, 71.93; H, 5.55; N, 3.36%.
Found: C, 71.78; H, 5.70; N, 3.95%.
4.6. 2-Amino-20,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-
4,30-indoline]-3-carbonitrile (4e)
White solid (0.29 g, 94%). Mp 251–252 ꢀC, IR (KBr) (nmax, cmꢁ1):
3365, 3284, 3161, 2194, 1722, 1653, 1349, 1213. MS, m/z (%): 307
(Mþ, 50), 251 (100), 209 (50), 140 (55), 39 (30). 1H NMR
(300.13 MHz, DMSO-d6): d (ppm) 1.90 (2H, br s, CH2), 2.20 (2H, br s,
CH2), 2.64 (2H, br s, CH2), 6.75–7.12 (4H, m, ArH), 7.21 (2H, s, NH2),
10.39 (1H, s, NH). 13C NMR (75.47 MHz, DMSO-d6): dC (ppm) 20.24
(CH2), 27.17 (CH2), 36.81 (CH2), 47.31, 57.93, 109.58, 112.31 (CN),
122.1, 123.64, 128.57, 134.98, 142.43, 159.06, 166.48, 178.58 (C]O,
amide), 195.47 (C]O). Anal. Calcd for C17H13N3O3: C, 66.44; H, 4.26;
N, 13.67%. Found: C, 66.31; H, 4.43; N, 13.84%.
4.11. 20-Amino-2,50-dioxo-50,60,70,80-tetrahydro-2H-
spiro[acenaphthylene-1,40-chromene]-30-carbonitrile (6c)
Orange solid (0.26 g, 75%). Mp 245–247 ꢀC, IR (KBr) (nmax
,
4.7. Ethyl-2-amino-20,5-dioxo-5,6,7,8-tetrahydrospiro-
[chromene-4,30-indoline]-3-carboxylate (4f)
cmꢁ1): 3372, 3189, 2192, 1718, 1672, 1595, 1344, 1205. MS, m/z (%):
342 (Mþ, 23), 230 (70), 202 (50), 175 (40), 84 (30), 42 (100). 1H
NMR (300.13 MHz, DMSO-d6): dH (ppm) 1.92 (2H, m, CH2), 2.15
(2H, m, CH2), 2.71 (2H, m, CH2), 7.32–8.66 (6H, m, ArH), 7.92 (2H, s,
NH2). 13C NMR (75.47 MHz, DMSO-d6): dC (ppm) 20.27 (CH2), 27.17
White solid (0.29 g, 83%). Mp 263–265 ꢀC, IR (KBr) (nmax, cmꢁ1):
3368, 3245, 3161, 1696, 1649, 1522, 1298. MS, m/z (%): 354 (Mþ, 40),

M. Dabiri et al. / Tetrahedron 65 (2009) 9443–9447
9447
(CH2), 36.50, 51.46, 58.50, 113.55, 117.99 (CN), 120.47, 121.81, 124.95,
Supplementary data
128.90, 129.33, 130.19, 131.86, 132.67, 140.87, 143.82, 159.10, 166.93,
195.87 (C]O), 204.06 (C]O). Anal. Calcd for C21H14N2O3: C, 73.68;
H, 4.12; N, 8.18%. Found: C, 73.54; H, 4.28; N, 8.34%.
Copy of 1H NMR and 13C NMR spectra for some compounds is
available. Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2009.08.070.
4.12. Ethyl-20-amino-2,50-dioxo-50,60,70,80-tetrahydro-2H-
spiro[acenaphthylene-1,40-chromene]-30-carboxylate (6d)
References and notes
Yellow solid (0.34 g, 87%). Mp 225–227 ꢀC, IR (KBr) (nmax, cmꢁ1):
3400, 3295, 2989, 1726, 1677, 1520, 1354. MS, m/z (%): 389 (Mþ, 20),
316 (100), 176 (80), 149 (40), 55 (25). 1H NMR (300.13 MHz, CDCl3):
dH (ppm) 0.04 (3H, t, J¼7.1 Hz, CH3), 1.47 (2H, m, CH2), 2.65 (2H, t,
J¼6.2 Hz, CH2), 3.45 (2H, q, J¼7.1 Hz, CH2), 4.52 (2H, t, J¼7.1 Hz,
CH2), 6.58 (2H, s, NH2), 7.22–8.48 (6H, m, ArH). 13C NMR
(75.47 MHz, CDCl3): dC (ppm) 12.25 (CH3), 27.43 (CH2), 36.82 (CH2),
59.43 (CH2), 63.40 (CH2), 75.09, 119.40, 119.90, 122.78, 124.21,
127.80, 127.99, 128.72, 128.83, 129.50, 129.61, 129.71, 132.21, 136.02,
141.23, 164.17 (C]O, ester), 168.32 (C]O), 195.60 (C]O). Anal.
Calcd for C23H19NO5: C, 70.94; H, 4.92; N, 3.60%. Found: C, 70.75; H,
5.12; N, 3.78%.
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4.13. 3,3,6,6-Tetramethyl-3,4,6,7-tetrahydro-1H-spiro-
[acridine-9,30-indoline]-1,20,8(2H,5H,10H)-trione (7)
Yellow solid (0.25 g, 65%). Mp 95–98 ꢀC, IR (KBr) (nmax, cmꢁ1):
3351, 2859, 1720, 1685, 1612, 1368, 1230, 975. MS, m/z (%): 391
(Mþþ1, 100), 307 (70), 270 (60), 83 (85), 41 (80). 1H NMR
(300.13 MHz, DMSO-d6): dH (ppm) 0.90–1.04 (12H, 4s, 4CH3), 1.86–
2.54 (8H, m, 4CH2), 4.11 (1H, s, NH), 6.67–7.42 (4H, m, ArH), 10.99
(1H, s, NH). 13C NMR (75.47 MHz, DMSO-d6): dC (ppm) 26.42 (CH3),
27.27 (CH3), 29.13 (CH3), 31.55 (CH3), 32.78, 33.68, 42.65 (CH2),
46.86 (CH2), 47.25 (CH2), 50.60 (CH2), 54.19, 59.08, 101.37, 109.80,
111.67, 121.63, 121.95, 127.97, 133.52, 144.72, 168.65, 182.26 (C]O,
amide), 194.66 (C]O), 203.90 (C]O). Anal. Calcd for C24H26N2O3:
C, 73.82; H, 6.71; N, 7.17%. Found: C, 73.64; H, 6.89; N, 7.35%.
4.14. 30,30,60,60-Tetramethyl-30,40,60,70-tetrahydro-10H,2H-spiro-
[acenaphthylene-1,90-acridine]-10,2,80(20H,50H,100H)-trione (8)
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White solid (0.25 g, 60%). Mp 244–245 ꢀC, IR (KBr) (nmax, cmꢁ1):
3255, 2959, 1718, 1688, 1658, 1612, 1230, 781. MS, m/z (%): 425 (Mþ,
20), 343 (100), 317 (30), 261 (45), 150 (65), 83 (95), 41 (85). 1H NMR
(300.13 MHz, CDCl3): dH (ppm) 1.06 (3H, s, CH3), 1.07 (3H, s, CH3),
1.11 (3H, s, CH3), 1.14 (3H, s, CH3), 2.00–2.52 (8H, m, 4CH2), 3.86 (1H,
s, NH), 7.12–8.16 (6H, m, ArH). 13C NMR (75.47 MHz, CDCl3): dC
(ppm) 26.92 (CH3), 26.98 (CH3), 29.27 (CH3), 31.50 (CH3), 33.14,
33.88, 43.10 (CH2), 47.80 (CH2), 50.15 (CH2), 51.40 (CH2), 54.21,
63.32, 100.68, 114.25, 117.34, 121.02, 125.02, 127.83, 128.23, 130.08,
131.04, 134.81, 141.96, 142.58, 168.51, 195.25 (C]O), 202.70 (C]O),
209.36 (C]O). Anal. Calcd for C28H27NO3: C, 79.03; H, 6.40; N,
3.29%. Found: C, 78.76; H, 6.67; N, 3.56%.
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2008, 9, 785–788.
38. Barthakur, M. G. Synlett 2007, 1475–1476.
Acknowledgements
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2006, 36, 2287–2292.
The authors would like to acknowledge financial support from
the Research Council of Shahid Beheshti University.