Gold(III) chloride (HAuCl4·3H2O) in PEG: A new and efficient catalytic system for the synthesis of functionalized spirochromenes

Article abstract of DOI:10.1016/j.apcata.2012.02.043

Gold(III) chloride (HAuCl₄·3H₂O) in PEG 400 was found to be an efficient catalytic system for the synthesis of biologically important functionalized spirochromene derivatives via one-pot three-component reaction of isatins/acenaphthoquinone, active methylene compounds and cyclic 1,3-diketones/4-hydroxycoumarin. A new catalytic system, recyclability of reaction medium, little reaction times and excellent yields with easy workup render this protocol more attractive and economically viable.

Full text of DOI:10.1016/j.apcata.2012.02.043

Applied Catalysis A: General 425–426 (2012) 35–43
Contents lists available at SciVerse ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Gold(III) chloride (HAuCl ·3H O) in PEG: A new and efficient catalytic system for
4
2
the synthesis of functionalized spirochromenes
Mazaahir Kidwai ,1, Anwar Jahan, Neeraj Kumar Mishra
∗
Green Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi 110007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Gold(III) chloride (HAuCl ·3H O) in PEG 400 was found to be an efficient catalytic system for the syn-
4
2
Received 12 December 2011
Received in revised form 24 February 2012
Accepted 25 February 2012
Available online 5 March 2012
thesis of biologically important functionalized spirochromene derivatives via one-pot three-component
reaction of isatins/acenaphthoquinone, active methylene compounds and cyclic 1,3-diketones/4-
hydroxycoumarin. A new catalytic system, recyclability of reaction medium, little reaction times and
excellent yields with easy workup render this protocol more attractive and economically viable.
©
2012 Elsevier B.V. All rights reserved.
Keywords:
Multicomponent reaction (MCR)
Isatins or Acenaphthoquinone
Active methylene compounds
Cyclic 1,3-diketones
Gold(III) chloride (HAuCl4·3H2O)
Polyethylene glycol (PEG)
Spirochromenes
1
. Introduction
heterocyclic spirooxindole ring system is a widely distributed
structural framework of many pharmaceuticals and natural prod-
ucts [7]. For example, spirotryprostatins A, B are a natural alkaloids
isolated from the fermentation broth of Aspergillus fumigates in
which spirotryprostatins B has been shown to completely inhibit
the G2/M progression of mammalian tsFT210 cells at concentra-
tions over 12.5 ␮g/mL [8] and polycyclic alkaloids pteropodine and
isopteropodine have a long history for its medicinal applications
in modulating the function of muscarinic serotonin receptors [9]
(Fig. 1). Among them oxygen-containing heterocycles fused with
spirooxindole ring system, functionally substituted 4H-chromenes
have been received considerable attention due to a wide range
of biological properties like anticoagulant, diuretic, anticancer and
antianaphylactic activities [10].
The evaluation of eco-friendly synthetic methodologies to facili-
tate the preparation of compound libraries is a pivotal focal point of
research activity in the field of modern medicinal and combinato-
rial chemistry [1]. One approach to address this challenge involves
the development of multicomponent reactions (MCRs) in which at
least three easily accessible components react to each other to form
a single product in a one-pot reaction flask, incorporating essen-
tially all atoms of the starting materials [2]. As one-pot reaction,
MCRs show high atom-economy, high selectivity and procedural
simplicity due to the formation of C–C and C-heteroatom bonds
[
3]. The growing interest for an environmentally benign multi-
component procedure is closely related to the development for the
synthesis of combinatorial small-molecule heterocyclic libraries
which is becoming an important and promising area of current
organic synthesis [4].
Compounds containing indole moiety exhibit antibacterial
and antifungal activities [5]. Furthermore, it has been reported
that using of the indole 3-carbon in the formation of spiroin-
doline derivatives highly enhances biological activity [6]. The
There are several methods have been reported for the
synthesis of spirooxindoles with fused chromenes in which
conventional synthesis involves one-pot, three-component con-
densation of isatin with cyclic 1,3-diketones and malononitrile or
2-aminobenzothiazole [11]. Shanthi et al. has reported a three-
component reaction for the synthesis of spirooxindole derivatives
catalyzed by InCl3 with 70–90% yields [12]. This reaction was also
carried out in the presence of p-TSA within 1 h under reflux con-
ditions [13]. Other more effective procedure for the synthesis of
spirooxindoles employed quaternary cationics [14], and electro-
chemical methods [15]. Thus, each of the known procedures for the
∗ Corresponding author. Tel.: +91 11 27666235; fax: +91 11 27666235.
E-mail address: kidwai.chemistry@gmail.com (M. Kidwai).
Presently Vice-Chancellor, Jiwaji University, Gwalior, M.P., India. (On Deputation
ꢀ
1
synthesis of corresponding spiro[(4H-chromene)-4,3 -oxindole]
from Department of Chemistry, University of Delhi, Delhi 110007, India).
has its merits, however, further studies are still necessary for the
0
926-860X/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2012.02.043

3
6
M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
O
O
H
O
O
HN
HN
N
N
N
N
H
O
O
H
O
Spirotryprostatin A
Spirotryprostatin B
Me
Me
N
O
N
O
H
H
H
H
H
H
O
O
N
O
N
O
OCH3
OCH3
H
H
Pteropodine
Isopteropodine
Fig. 1. Biologically active spirooxindole containing compounds.
essence of a new facile, efficient, environmental and economical
multicomponent methodology for the synthesis of these hetero-
cyclic compounds.
to afford a series of spirooxindole derivatives in polyethylene gly-
col (PEG) as recyclable solvent media catalyzed by gold(III) chloride
◦
(HAuCl ·3H O) at 70 C.
4
2
In recent years, gold catalyzed reactions have focused not only
on the development of new processes, but also on improving
the sustainability of existing transformations such as cycload-
dition, isomerisation, hydroamination or nucleophilic cyclization
of allenes [16]. In transition metal catalysis, cationic gold(I) and
gold(III) salts are soft carbophilic Lewis acids, have shown extraor-
dinary capability of activating C–C double and triple bond for an
inter or intra molecular nucleophilic attack to form a new C–C
and C–X bond forming reactions [17]. On the other hand, the
versatility of homogeneous mixture of PEG and gold(III) chloride
2. Experimental
2.1. General Information
All of the chemicals were purchased from Sigma-Aldrich and
used without further purification. Most of the synthesized com-
pounds are reportedly known and were identified by comparison
of spectral and physical data with the literature. IR spectra were
recorded on Perkin Elmer FTIR spectrophotometer using KBr pel-
lets. IR frequency, max is measured in cm . H NMR and C NMR
(400 and 100 MHz, respectively) spectra were recorded on Jeol JNM
ECX-400P Spectrometer using TMS as an internal standard. The
chemical shift values are recorded on ␦ scale and the coupling con-
stants (J) are in hertz. Mass spectral data were recorded on a Waters
micromass LCT Mass Spectrometer. Temperature of the reaction
mixture was measured through AZ, Mini Gun Type, Non-Contact
IR thermometer, Model No. 8868. The melting points were deter-
mined on Thomas Hoover melting point apparatus. The purity of
the compounds was checked on TLC (silica gel coated aluminium
sheets, Silica gel 60 F254, E. Merck, Germany).
ꢀ
−1
1
13
(
HAuCl ·3H O) encouraged us to couple them together to evaluate
4
2
their utility as a novel and highly efficient catalytic system for the
synthesis of spirooxindole derivatives.
Due to increasing awareness of environmental problems for the
synthetic chemists in chemical research and industry, efforts have
been made to develop an environmentally benign chemical syn-
thesis both in academia and chemical research. In this situation,
the search for an alternative reaction media which replace toxic
and traditional volatile organic compounds (VOCs) with various
aqueous solutions have been attracted much attention in organic
synthesis and industrial research [18]. Meanwhile, water used as
environmentally benign solvent has been well documented for
organic reactions [19] but the practical utilization is limited due to
the hydrophobic nature of organic compounds and the sensitivity
of catalysts towards moisture. So we decided to use polyethylene
glycol (PEG) as the reaction media, as it may stand in comparison to
other currently favoured systems such as ionic liquids, super criti-
cal carbon dioxide and micellar systems [20]. Recently, PEGs have
been explored as a novel, powerful, eco-friendly solvent medium
and supporter for various organic transformations due to their rel-
atively inexpensive, thermal stable, recyclable and biodegradable
material [21].
2.2. General procedure for the synthesis of functionalized
spirochromenes derivatives
In a 50 mL round bottom flask, a mixture of isatin 1a–1d or
acenaphthoquinone 6 (1 mmol), active methylene compounds 2a
and 2b (1 mmol) and HAuCl ·3H O (5 mol%) in polyethylene gly-
4
2
col (PEG 400) (5 mL) were placed over a magnetic stirrer and the
contents were stirred. To this stirred mixture, cyclic 1,3-diketones
3a–3c/4-hydroxycoumarin 3d (1 mmol) was added. The reaction
◦
mixture was heated at 70 C for 30 min. The progress of the reac-
In this continuation to our ongoing endeavor and aimed to
developed an environmentally benign synthetic methods for phar-
macologically important skeletons [22]. Herein, we wish to report a
new and efficient protocol for one-pot three-component reaction of
isatins with active methylene compounds and cyclic 1,3-diketones
tion mixture was monitored by TLC using hexane-ethyl acetate
(2:1) as an eluent. After completion of the reaction, the reaction
mixture was allowed to cool in dry ice-bath to precipitate the PEG
400 and extracted with ether (PEG being insoluble in ether). The
combined ether layer was filtered in order to recover the PEG. The

M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
37
filtrate was mixed with water and dried over anhydrous sodium
sulfate (Na SO ) and concentrated under reduced pressure. The
2.63–2.66 (m, 2H, CH ), 2.18–2.22 (m, 2H, CH ), 1.89–1.92 (m, 2H,
2 2
13
CH ); C NMR (100 MHz, DMSO-d ) ı = 194.98, 176.55, 166.15,
2
4
2
6
crude product was washed with cool ethanol (3 × 10 mL) and dried.
Further, the product was purified by silica-gel column chromatog-
raphy using 20% ethylacetate and 80% hexane as an eluent to yield
the desired products. The recovered PEG 400 can be reused for
further reactions. The structures of all the products were unam-
biguously established on the basis of their spectral analysis (IR,
H NMR, C NMR and ESI-MS mass spectral data). The melting
points of the known synthesized products are identical with those
reported previously [11a,14,15a,23].
158.64, 143.60, 133.82, 128.57, 123.11, 122.49, 117.34, 111.99,
108.08, 56.82, 47.52, 37.32, 27.07, 26.23, 19.84; m/z 321.3300
(M + 1, C18H15N O requires 321.1113).
3
3
ꢀ
ꢀ
2-Amino-1 -methyl-2 ,5-dioxo-6,7-dihydro-5H-
spiro[cyclopenta[b]pyran-4,3 -indoline]-3-carbonitrile
White solid; mp: 279–280 C; IR (KBr): max = 3566, 3456, 3345,
3140, 2960, 2195, 1706, 1675, 1498, 1350, 1216, 1190, 1078,1016,
756; 1H NMR (400 MHz, DMSO-d ) ı = 7.29–7.45 (m, 3H, NH ,
ꢀ
(4f):
◦
ꢀ
1
13
6
2
ArH), 7.10 (d, J = 7.1 Hz, 1H, ArH), 7.01–7.03 (m, 2H, ArH), 3.18
(
s, 3H, CH ), 2.85 (t, J = 4.0 Hz, 2H, CH ), 2.28–2.32 (m, 2H, CH );
C NMR (100 MHz, DMSO-d ) ␦ = 199.72, 177.56, 176.15, 160.82,
6
3
2
2
1
3
2.3. Spectral data of synthesized functionalized spirochromenes
(
4a–4n, 4a–4d and 7a–7f)
142.62, 132.24, 128.23, 124.12, 122.54, 117.30, 115.26, 108.10,
6.38, 47.51, 36.30, 27.23, 26.36; m/z 307.3034 (M + 1, C17H13N O3
5
3
ꢀ
2
-Amino-7,7-dimethyl-2 ,5-dioxo-5,6,7,8-
requires 307.0957).
1 -Acetyl-2-amino-7,7-dimethyl-2 ,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4g):
White Solid; mp: 230–232 C; IR (KBr): max = 3462, 3194, 2933,
2193, 1757, 1726, 1663, 1354, 1256, 1099 cm
d , 400 MHz): ı = 8.07 (d, J = 8.1 Hz, 1H, ArH), 7.52 (br s, 2H, NH ),
ꢀ
ꢀ
ꢀ
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4a):
White solid; mp: 288–289 C; IR (KBr): max = 3377, 3314, 3142,
◦
ꢀ
ꢀ
−
1
◦
ꢀ
2
960, 2192, 1720, 1659, 1605, 1472, 1348, 1227, 1055, 924 cm
;
1
−1
1
H NMR (DMSO-d , 400 MHz): ␦ = 10.32 (s, 1H, NH), 7.14 (br s, 2H,
; H NMR (DMSO-
6
NH ), 7.06 (t, J = 7.8 Hz, 1H, ArH), 6.89 (d, J = 7.3 Hz, 1H, ArH), 6.81
2
6
2
(
t, J = 7.7 Hz, 1H, ArH), 6.70 (d, J = 7.8 Hz, 1H, ArH), 2.49 (d, J = 3.7 Hz,
7.27–7.36 (m, 1H, ArH), 7.18–7.22 (m, 2H, ArH), 2.66 (s, 3H, CH CO),
3
2
0
H, CH ), 2.12 (d, J = 16.1 Hz, 1H, CH), 2.04 (d, J = 16.1 Hz, 1H, CH),
2.55 (s, 2H, CH ), 2.48–2.49 (m, 2H, CH ), 1.03 (s, 3H, CH ), 0.99
2
2
13
2
3
13
.95 (s, 3H, CH ), 0.92 (s, 3H, CH ); C NMR (DMSO-d , 100 MHz):
(s, 3H, CH ); C NMR (DMSO-d , 100 MHz): ı = 195.41, 177.84,
3
3
6
3
6
ı = 194.91, 178.05, 164.16, 158.78, 142.06, 134.42, 128.19, 123.02,
170.24, 164.93, 158.74, 139.17, 132.71, 128.67, 125.50, 123.30,
116.93, 115.30, 110.75, 56.96, 49.47, 47.39, 39.91, 32.12, 27.53,
27.02, 25.95; m/z 377.3933 (M + 1, C21H19N O requires 377.1376).
1
2
21.70, 117.34, 110.79, 109.26, 57.52, 50.01, 46.83, 31.95, 27.61,
7.04; m/z 335.3566 (M + 1, C19H17N O requires 335.1270).
3
3
3
4
ꢀ
ꢀ
ꢀ
ꢀ
2
-Amino-2 ,5-dioxo-5,6,7,8-tetrahydrospiro[chromene-4,3 -
1 -Acetyl-2-amino-2 ,5-dioxo-5,6,7,8-
◦
ꢀ
indoline]-3-carbonitrile (4b): White solid; mp: > 300 C; IR (KBr):
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4h):
ꢀ
◦
ꢀ
max = 3462, 3291, 3169, 2933, 2194, 1714, 1666,1612, 1468,
White Solid; mp: 253–255 C; IR (KBr): max = 3462, 3326, 2933,
−1 1
; H NMR (DMSO-d , 400 MHz):
6
2194, 1756, 1725, 1667, 1336, 1256, 1166, 1064; 1H NMR (DMSO-
1
392, 1214, 1064, 1012, 931 cm
ı = 10.37 (s, 1H, NH), 7.17 (br s, 2H, NH ), 7.08 (t, J = 8.6 Hz, 1H,
d , 400 MHz): ı = 8.01 (d, J = 8.0 Hz, 1H, ArH), 7.44 (br s, 2H, NH ),
6 2
2
ArH), 6.94 (d, J = 7.8 Hz, 1H, ArH), 6.83 (t, J = 7.3 Hz, 1H, ArH), 6.74
7.23–7.26 (m, 1H, ArH), 7.03–7.16 (m, 2H, ArH), 2.54–2.64 (m,
2H, CH ), 2.24–2.39 (m, 2H, CH ), 2.49 (s, 3H, CH CO), 2.13–2.21
(
d, J = 7.3 Hz, 1H, ArH), 2.43–2.60 (m, 2H, CH ), 2.18–2.24 (m, 2H,
2
2
2
3
13
13
CH ), 1.85–1.90 (m, 2H, CH );
C NMR (DMSO-d , 100 MHz):
(m, 2H, CH ); C NMR (DMSO-d , 100 MHz): ı = 195.44, 178.08,
2
2
6
2
6
ı = 194.74, 178.34, 166.38, 158.60, 141.92, 134.41, 128.17, 123.99,
21.67, 117.45, 111.61, 109.18, 57.68, 47.84, 36.28, 26.82, 19.31;
m/z 307.3034 (M + 1, C17H13N O requires 307.0957).
170.25, 166.66, 158.52, 139.12, 133.02, 128.64, 125.51, 123.48,
117.06, 115.03, 111.74, 56.98, 47.44, 35.91, 26.60, 25.95, 19.70;
m/z 349.1063 (M + 1, C H15N O requires 349.0880).
1
3
3
19
3
4
ꢀ
ꢀ
ꢀ
2
-Amino-2 ,5-dioxo-6,7-dihydro-5H-
1 -Acetyl-2-amino-2 ,5-dioxo-6,7-dihydro-5H-
ꢀ
ꢀ
spiro[cyclopenta[b]pyran-4,3 -indoline]-3-carbonitrile
White solid; mp: > 300 C; IR (KBr): max = 3352, 3240, 3165,
(4c):
spiro[cyclopenta[b]pyran-4,3 -indoline]-3-carbonitrile
(4i):
◦
ꢀ
◦
ꢀ
White Solid; mp: 282–284 C; IR (KBr): max = 3463, 3324, 2919,
2198, 1752, 1721, 1665, 1324, 1253, 1168, 1071, 910, 757; H NMR
1
2
6
917, 2223, 1713, 1649, 1592, 1469, 1337, 1214, 1013, 907, 749,
−1 1
20 cm ; H NMR (DMSO-d , 400 MHz): ı = 10.54 (s, 1H, NH), 7.47
(DMSO-d , 400 MHz): ı = 8.02 (d, J = 8.1 Hz, 1H, ArH), 7.70 (br s,
6
6
(
br s, 2H, NH ), 7.18 (t, J = 7.6 Hz, 1H, ArH), 7.04 (d, J = 6.6 Hz, 1H,
2H, NH ), 7.27–7.31 (m, 1H, ArH), 7.13–7.20 (m, 2H, ArH), 2.77 (t,
2
2
ArH), 6.91 (t, J = 7.3 Hz, 1H, ArH), 6.80 (d, J = 7.3 Hz, 1H, ArH), 2.79
J = 4.7 Hz, 2H, CH ), 2.49 (s, 3H, CH CO), 2.31 (t, J = 5.0 Hz, 2H, CH );
C NMR (DMSO-d , 100 MHz): ı = 200.13, 177.98, 170.32, 163.15,
6
2
3
2
13
13
(
t, J = 4.0 Hz, 2H, CH ), 2.33–2.35 (m, 2H, CH ); C NMR (DMSO-d6,
2
2
1
1
2
00 MHz): ı = 199.79, 177.57, 176.56, 160.57, 141.97, 132.12,
28.83, 124.08, 122.87, 117.55, 114.83, 109.51, 56.45, 46.58, 33.19,
160.50, 139.44, 130.51, 129.39, 125.85, 124.53, 117.33, 115.57,
112.96, 56.03, 47.44, 34.62, 26.12, 25.18; m/z 335.3135 (M + 1,
C18H13N O requires 335.0906).
4.85; m/z 293.0800 (M + 1, C16
H
N O requires 293.2768).
11 3 3
3
4
ꢀ
ꢀ
ꢀ
ꢀ
2
-Amino-1 ,7,7-trimethyl-2 5-dioxo-5,6,7,8-
2-Amino-5 -chloro-2 ,5-dioxo-7,7-dimethyl-5,6,7,8-
ꢀ
ꢀ
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4d):
White solid; mp: 254–255 C; IR (KBr): max = 3459, 3234, 3139,
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4j):
◦
ꢀ
◦
ꢀ
White solid; mp: 288–290 C; IR (KBr): max = 3445, 3285, 3146,
2932, 2194, 1725, 1663, 1605, 1479, 1392, 1256, 1164, 1063,
2
933, 2193, 1708, 1667, 1605, 1496, 1391, 1256, 1142, 1063,
−1
1
−1
; H NMR (DMSO-d , 400 MHz): ı = 10.39 (s, 1H, NH),
6
1
9
12 cm
;
H NMR (DMSO-d , 400 MHz): ı = 7.21–7.26 (m, 3H,
905 cm
7.24 (br s, 2H, NH ), 7.12 (d, J = 8.0 Hz, 1H, ArH), 7.02 (s, 1H, ArH),
6
NH , ArH), 7.05 (d, J = 7.8 Hz, 1H, ArH), 7.00–6.96 (m, 2H, ArH),
2
2
3
1
.35 (s, 3H, CH ), 2.49–2.56 (m, 2H, CH ), 2.04–2.16 (m, 2H, CH ),
6.71 (d, J = 8.8 Hz, 1H, ArH), 2.41–2.53 (m, 2H, CH ), 2.03–2.11 (m,
3
2
2
2
13
13
.01 (s, 3H, CH ), 0.97 (s, 3H, CH ); C NMR (DMSO-d , 100 MHz):
2H, CH ), 0.94 (s, 3H, CH ), 0.90 (s, 3H, CH ); C NMR (DMSO-d6,
3
3
6
2
3
3
ı = 195.06, 176.69, 164.26, 158.93, 143.53, 133.56, 128.54, 122.88,
100 MHz): ␦ = 195.01, 177.77, 164.51, 158.86, 141.02, 136.43,
1
22.27, 117.24, 110.67, 108.31, 57.53, 50.43, 46.82, 32.09, 27.08,
128.15, 125.72, 123.18, 117.14, 110.70, 110.12, 56.33, 50.48, 46.80,
2
7.09, 25.97; m/z 349.3832 (M + 1, C20H19N O requires 349.1426).
32.00, 27.52, 27.23; m/z 369.8016 (M + 1, C19H16ClN O3 requires
3
3
3
ꢀ
ꢀ
2
-Amino-1 -methyl-2 ,5-dioxo-5,6,7,8-
369.0880).
ꢀ
ꢀ
ꢀ
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4e):
White solid; mp: 248–249 C; IR (KBr): max = 3565, 3466, 3355,
2-Amino-5 -chloro-2 ,5-dioxo-5,6,7,8-
tetrahydrospiro[chromene-4,3 -indoline]-3-carbonitrile (4k):
◦
ꢀ
ꢀ
◦
ꢀ
3
145, 2962, 2195, 1702, 1676, 1331, 1216, 1196, 1075,1013, 757;
White solid; mp: 293–295 C; IR (KBr): max = 3468, 3287, 3142,
2932, 2116, 1722, 1668,1608, 1497, 1391, 1256, 1162, 1063,
1
H NMR (400 MHz, DMSO-d ) ı = 7.19–7.24 (m, 3H, NH , ArH), 7.06
6
2
−
1
1
(
d, J = 7.6 Hz, 1H, ArH), 6.94–6.98 (m, 2H, ArH), 3.20 (s, 3H, CH ),
908 cm
;
HNMR (DMSO-d , 400 MHz): ı = 10.49 (s, 1H, NH),
3
6

3
8
M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
7
6
2
.26 (br s, 2H, NH ), 7.15 (d, J = 7.9 Hz, 1H, ArH), 7.10 (s, 1H, ArH),
2 -Amino-1-methyl-2,5 -dioxo-5 H-spiro[indoline-3,4 -
2
.74 (d, J = 8.0 Hz, 1H, ArH), 2.45–2.60 (m, 2H, CH ), 2.00–2.20 (m,
pyrano[3,2-c]chromene]-3 -carbonitrile (5c): White solid; mp:
283–285 C; IR (KBr): max = 3456, 3291, 3168, 2915, 2227,
1719,1664, 1607, 1465, 1373, 1223, 1127, 1099, 949 cm
NMR (DMSO-d , 400 MHz): ␦ = 7.91 (d, J = 7.8 Hz, 1H, ArH), 7.64 (t,
2
13
◦
ꢀ
H, CH ), 1.85–1.91 (m, 2H, CH ); C NMR (DMSO-d , 100 MHz):
2
2
6
−
1
1
ı = 195.24, 177.97, 166.66, 158.78, 140.96, 136.53, 128.02, 125.58,
23.42, 117.17, 111.29, 110.48, 56.79, 47.06, 32.01, 26.86, 19.56;
;
H
1
6
m/z 341.7485 (M + 1, C1
H
ClN O3 requires 341.0567).
J = 8.5 Hz, 1H, ArH), 7.57 (br s, 2H, NH ), 7.53 (t, J = 7.8 Hz, 1H, ArH),
7
12
3
2
ꢀ
ꢀ
2
-Amino-5 -chloro-2 ,5-dioxo-6,7-dihydro-5H-
7.33 (d, J = 8.0 Hz, 1H, ArH), 7.31 (t, J = 7.8 Hz, 1H, ArH), 7.29 (d,
J = 6.6 Hz, 1H, ArH), 7.05 (d, J = 7.8 Hz, 1H, ArH), 7.0 (t, J = 6.6 Hz, 1H,
ꢀ
spiro[cyclopenta[b]pyran-4,3 -indoline]-3-carbonitrile
(4l):
◦
ꢀ
13
White solid; mp: > 300 C; IR (KBr): max = 3465, 3282, 3135, 2915,
ArH), 3.14 (s, 3H, CH ); C NMR (DMSO-d , 100 MHz): ı = 171.75,
3
6
−
1
2
191, 1720, 1671, 1466, 1213, 1158, 1098, 1010, 912, 753 cm
;
162.38, 158.62, 155.69, 149.78, 147.31, 137.63, 132.28, 128.56,
125.54, 124.25, 123.45, 118.05, 117.96, 112.95, 111.58, 110.53,
1
H NMR (DMSO-d , 400 MHz): ı = 10.70 (s, 1H, NH), 7.57 (br s,
6
2
2
H, NH ), 7.20–7.24 (m, 2H, ArH), 6.84 (d, J = 7.8 Hz, 1H, ArH),
57.12, 47.62, 26.11; m/z 371.3456 (M + 1, C21H13N O requires
2
3 4
13
.78–2.80 (m, 2H, CH ), 2.36–2.49 (m, 2H, CH ); C NMR (DMSO-
371.0906).
2
2
ꢀ
ꢀ
ꢀ
ꢀ
d6, 100 MHz): ␦ = 199.95, 178.00, 176.57, 160.73, 141.73, 136.94,
2 -Amino-5-chloro-2,5 -dioxo-5 H-spiro[indoline-3,4 -
ꢀ
1
34.09, 128.81, 124.52, 117.43, 114.22, 110.98, 55.88, 46.79, 33.20,
pyrano[3,2-c]chromene]-3 -carbonitrile (5d): White solid; mp:
◦
ꢀ
2
5.01; m/z 327.7219 (M + 1, C16H10ClN O3 requires 327.0413).
>300 C; IR (KBr): max = 3459, 3322, 3210, 2932, 2196,1713,1667,
3
ꢀ
−1
1
Ethyl
2-Amino-7,7-dimethyl-2 ,5-dioxo-5,6,7,8-
1605, 1440, 1391, 1256, 1171, 1098, 971 cm
; H NMR (DMSO-
ꢀ
tetrahydrospiro[chromene-4,3 -indoline]-3-carboxylate (4m):
White solid; mp: 256–257 C, IR (KBr): max = 3429, 2997, 2128,
d6, 400 MHz): ı = 10.80 (s, 1H, NH), 7.93 (d, J = 7.6 Hz, 1H, ArH),
◦
ꢀ
7.72–7.77 (m, 3H, ArH, NH ), 7.53 (t, J = 7.3 Hz, 1H, ArH), 7.47 (d,
2
−
1 1
1
4
4
2
3
686, 1620, 1473, 1222, 1027, 952, 762 cm
;
H NMR (DMSO-d6,
J = 8.1 Hz, 1H, ArH), 7.41 (s, 1H, ArH), 7.26 (d, J = 8.1 Hz, 1H, ArH), 6.84
00 MHz): ı = 10.24 (s, 1H, NH), 7.72 (br s, 2H, NH ), 6.71–7.08 (m,
(d, J = 7.3 Hz, 1H, ArH); 13C NMR (DMSO-d , 100 MHz): ı = 176.91,
2
6
H, ArH), 3.64 (q, J = 5.1 Hz, 2H, CH ), 2.51 (d, J = 3.5 Hz, 2H, CH ),
.13 (d, J = 15.2 Hz, 1H, CH), 2.06 (d, J = 15.2 Hz, 1H, CH), 1.03 (s,
H, CH ), 0.94 (s, 3H, CH ), 0.82 (t, J = 6.6 Hz, 3H, CH ); C NMR
159.02, 158.39, 155.43, 152.30, 141.01, 134.92, 133.71, 128.74,
126.10, 124.97, 124.50, 122.65, 116.88, 116.64, 112.71,110.79,
2
2
13
100.69, 56.36, 47.85; m/z 391.7641 (M + 1, C20H10ClN O4 requires
3
3
3
3
(
1
5
DMSO-d6, 100 MHz): ı = 195.18, 179.80, 168.23, 162.81, 159.65,
43.32, 134.12, 127.41, 123.01, 121.62, 114.36, 109.12, 78.58,
9.61, 52.32, 46.85, 34.09, 27.39, 27.11, 13.65; m/z 382.4098 (M + 1,
391.0360).
ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ ꢀ
2 -Amino-7 ,7 -dimethyl-2,5 -dioxo-5 ,6 ,7 ,8 -tetrahydro-
ꢀ ꢀ
2H-spiro[acenaphthylene-1,4 -chromene]-3 -carbonitrile (7a):
Light yellow solid; mp: 261–263 C; IR (KBr): max = 3468, 3186,
2932, 2192, 1718, 1663, 1497, 1256, 1098 cm
d6, 400 MHz): ı = 8.41–8.44 (m, 1H. ArH), 8.24 (d, J = 7.4 Hz, 1H,
ArH), 8.17 (d, J = 7.6 Hz, 1H, ArH), 7.91–8.01 (m, 3H, ArH), 7.31 (br s,
◦
ꢀ
C21H22N O5 requires 382.1529).
2
ꢀ
−1
1
Ethyl
2-Amino-2 ,5-dioxo-5,6,7,8-
; H NMR (DMSO-
ꢀ
tetrahydrospiro[chromene-4,3 -indoline]-3-carboxylate (4n):
White solid; mp: 262–263 C; IR (KBr): max = 3465, 3289, 2932,
1
◦
ꢀ
−
1
1
656, 1642, 1532, 1469, 1212, 1065, 1015, 934, 740 cm
;
H
2H, NH ), 2.47–2.49 (m, 2H, CH ), 2.11 (d, J = 16.1 Hz, 1H, CH), 2.06
2
2
13
NMR (DMSO-d , 400 MHz): ı = 10.37 (s, 1H, NH), 7.69 (br s,
(d, J = 16.0 Hz, 1H, CH), 1.02 (s, 3H, CH ), 1.4 (s, 3H, CH ); C NMR
6
3
3
2
1
H, NH ), 7.02–7.43 (m, 4H, ArH), 3.66 (q, J = 5.8 Hz, 2H, CH ),
(DMSO-d , 100 MHz): ı = 203.61, 195.34, 164.62, 158.65, 143.20,
140.48, 132.17, 131.52, 130.14, 129.84, 128.93, 124.51, 121.40,
119.84, 117.45, 112.05, 57.92, 51.04, 49.73, 32.09, 27.52, 27.20;
2
2
6
13
.95–2.83 (m, 6H, CH ), 0.76 (t, J = 6.9 Hz, 3H, CH );
C NMR
2
3
(
DMSO-d , 100 MHz): ␦ = 195.40, 178.43, 169.65, 165.12, 159.56,
6
1
5
C19
41.93, 134.42, 127.18, 123.94, 121.65, 115.84, 108.46, 77.95,
9.17, 47.36, 38.22, 27.62, 19.30, 13.51; m/z 354.3566 (M + 1,
m/z 370.4006 (M + 1, C23H N O requires 370.1317).
18
ꢀ
2
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2 -Amino-2,5 -dioxo-5 ,6 ,7 ,8 -tetrahydro-2H-
ꢀ
ꢀ
H
2
N O5requires 354.1216).
spiro[acenaphthylene-1,4 -chromene]-3 -carbonitrile
(7b):
18
2
ꢀ
ꢀ
ꢀ
ꢀ
◦
ꢀ
-Amino-2,5 -dioxo-5 H-spiro[indoline-3,4 -pyrano[3,2-
Orange solid; mp: 244–246 C; IR (KBr): max = 3490, 3072, 2931,
2116, 1720, 1672, 1498, 1389, 1256, 1064 cm
ꢀ
◦
−1
1
c]chromene]-3 -carbonitrile (5a): White solid; mp: 284–286 C;
IR (KBr): max = 3467, 3294, 3197, 2932, 2275, 1727, 1660, 1602,
1
4
; H NMR (DMSO-
ꢀ
d6, 400 MHz): ı = 8.40–8.44 (t, J = 8.0 Hz, 1H, ArH), 8.25 (d, J = 7.3 Hz,
1H, ArH), 8.18 (d, J = 7.3 Hz, 1H, ArH), 7.93–8.01 (m, 3H, ArH), 7.29
(br s, 2H, NH ), 2.48–2.49 (m, 2H, CH ) 2.13–2.18 (m, 2H, CH ),
−
1 1
543, 1496, 1391, 1256, 1172, 1099, 970 cm ; H NMR (DMSO-d ,
6
00 MHz): ␦ = 10.68 (s, 1H, NH), 7.94 (d, J = 7.8 Hz, 1H, ArH), 7.75
2
2
2
13
(
t, J = 7.3 Hz, 1H, ArH), 7.66 (br s, 2H, NH ), 7.40 (t, J = 7.8 Hz, 1H,
1.89–1.95 (m, 2H, CH ); CNMR (DMSO-d , 100 MHz): ı = 203.72,
2
2
6
ArH), 7.34 (d, J = 8.7 Hz, 1H, ArH), 7.20 (t, J = 7.8 Hz, 2H, ArH),
.92 (t, J = 7.8 Hz, 1H, ArH), 6.85 (d, J = 7.4 Hz, 1H, ArH); 13C NMR
DMSO-d , 100 MHz): ␦ = 177.26, 159.66, 158.49, 155.24, 152.13,
198.34, 168.30, 156.06, 143.39, 140.79, 132.20, 130.13, 129.43,
128.54, 123.66, 123.15, 122.86, 117.35, 113.19, 57.25, 51.30, 36.81,
27.14, 21.32; m/z 342.3475 (M + 1, C21H14N O requires 342.1004).
6
(
6
2
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1
1
42.19, 133.69, 132.91, 129.92, 125.05, 124.13, 123.09, 122.71,
17.11, 117.05, 112.57, 109.78, 101.51, 56.91, 47.63; m/z 357.3190
2 -Amino-2,5 -dioxo-6 ,7 -dihydro-2H,5 H-
ꢀ
ꢀ
spiro[acenaphthylene-1,4 -cyclopenta[b]pyran]-3 -carbonitrile
◦
ꢀ
(
M + 1, C20H11N O requires 357.0750).
(7c): Orange solid; mp: > 300 C; IR (KBr): max = 3440, 3072, 2933,
3
4
ꢀ
ꢀ
ꢀ
ꢀ
−1
1
Ethyl
2 -Amino-2,5 -dioxo-5 H-spiro[indoline-3,4 -
2117, 1722, 1613, 1495, 1385, 1223, 1026, 983, 780 cm
;
H
ꢀ
pyrano[3,2-c]chromene]-3 -carboxylate (5b): White Solid;
mp: 252–253 C; IR (KBr): max = 3455, 3282, 3015, 2920, 1725,
NMR (DMSO-d , 400 MHz): ı = 8.43 (t, J = 8.8 Hz, 1H, ArH), 8.34
6
◦
ꢀ
(d, J = 7.4 Hz, 1H, ArH), 8.17 (d, J = 7.4 Hz, 1H, ArH), 7.92–8.01 (m,
−
1
1
658, 1563, 1473, 1434, 1315, 1274, 1184, 1027, 949, 754 cm
;
3H, ArH), 7.57 (br s, 2H, NH ), 2.86–2.87 (m, 2H, CH ) 2.47–2.49
2
2
1
13
H NMR (DMSO-d , 400 MHz): ı = 10.40 (s, 1H, NH), 9.80 (br s, 2H,
(m, 2H, CH ); C NMR (DMSO-d , 100 MHz): ı = 203.09, 200.16,
6
2
6
NH ), 7.50–7.41 (m, 2H, ArH), 7.34 (t, J = 8.1 Hz, 1H, ArH), 7.26 (d,
177.84, 155.98, 141.31, 140.73, 132.33, 129.40, 129.09, 128.74,
125.08, 123.27, 122.05, 121.08, 117.70, 111.72, 56.99, 50.92, 33.10,
2
J = 8.04 Hz, 1H, ArH), 7.01–7.10 ((m, 2H, ArH), 6.77–6.83 (m, 2H,
13
ArH), 3.69–3.75 (m, 2H, CH O), 0.81 (t, J = 6.9 Hz, 3H, CH ); CNMR
25.06; m/z 328.3209 (M + 1, C
H
N O requires 328.0848).
2
3
20 12
2
3
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
(
DMSO-d , 100 MHz): ı = 170.24, 167.98, 166.06, 163.21, 159.85,
Ethyl
2 -Amino-7 ,7 -dimethyl-2,5 -dioxo-5 ,6 ,7 ,8 -
6
ꢀ
ꢀ
1
1
52.10, 142.43, 131.86, 128.57, 127.73, 126.86, 126.21, 125.35,
tetrahydro-2H-spiro[acenaphthylene-1,4 -chromene]-3 -
24.99, 124.23, 121.87, 120.29, 77.38, 59.62, 48.60, 13.85; 13CNMR
carboxylate (7d): White solid; mp: 263–264 C; IR (KBr):
◦
ꢀ
−1
;
(
DMSO-d , 100 MHz): ı = 177.28, 159.68, 158.53, 155.29, 152.17,
max = 3421, 3185, 2939, 2182, 1717, 1602, 1487, 1277, 1014 cm
6
1
1
1
42.16, 133.68, 132.986, 129.95, 125.08, 124.16, 123.15, 122.75,
17.18, 117.10, 112.58, 109.72, 101.49, 62.34, 56.95, 47.64, 14.45;
H NMR (DMSO-d , 400 MHz): ı = 7.52–8.41 (m, 6H. ArH), 7.90
6
(s, 2H, NH ), 4.48 (q, J = 6.1 Hz, 2H, CH ), 2.48–2.49 (m, 2H, CH ),
2
2
2
m/z 404.3722 (M + 1, C22H16N O requires 404.1008).
1.35–1.38 (m, 2H, CH ), 1.09 (s, 3H, CH ), 1.07 (s, 3H, CH ), 0.45
2
6
2 3 3

M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
39
Table 1
Table 2
Optimization of reaction conditions.a
Screening of solvent and temperature.
a
Yield (%)b
Entry
Solvent
Temp ( C)
◦
Time (min)
Yield (%)b
Entry
Catalyst
Amount (mol%)
Time (min)
1
2
3
4
5
6
7
8
9
–
–
5
5
5
5
5
5
5
5
600
210
360
120
450
270
300
180
180
30
24
43
38
73
25
47
50
30
30
93
96
95
1
2
3
4
5
6
7
8
C2H5OH
CH3CN
H2O
DMSO
DMF
Solvent-free
PEG 200
PEG 400
PEG 600
PEG 400
PEG 400
PEG 400
Reflux
Reflux
Reflux
Reflux
Reflux
70
70
70
70
80
355
240
240
650
650
650
30
30
30
30
120
120
76
ZnCl2
BiCl3
InCl3
FeCl3·6H2O
SnCl2·2H2O
p-TSA
<35
<35
Trace
Trace
Trace
94
96
96
96
60
AuCl
Ph3PAuCl
HAuCl4·3H2O
HAuCl4·3H2O
HAuCl4·3H2O
9
10
11
12
3
5
10
10
11
12
30
30
rt
40
70
a
a
Reaction conditions: Isatin 1a (1 mmol), malononitrile 2a (1 mmol), dimedone
Reaction conditions: isatin 1a (1 mmol), malononitrile 2a (1 mmol) dimedone 3a
(1 mmol); catalyst: gold(III) chloride (5 mol%); different solvents: (5 mL); at different
temperature.
3
7
a (1 mmol); solvent: PEG 400 (5 mL); different catalysts (5 mol%); temperature:
◦
0
C.
b
b
Isolated yields.
Isolated yields.
(
t, J = 6.8 Hz, 3H, CH ); 13C NMR (DMSO-d , 100 MHz): ı = 196.42,
3 6
95.25, 167.60, 164.98, 159.73, 145.26, 134.18, 132.41, 130.63,
29.79, 128.35, 128.09, 124.45, 121.66, 118.70, 114.30, 78.01,
8.61, 51.13, 50.15, 35.29, 29.22, 28.85, 13.56; m/z 418.2110 (M + 1,
such as ZnCl , BiCl , InCl , FeCl ·3H O, SnCl ·2H O, p-TSA, AuCl,
2
3
3
3
2
2
2
1
1
5
Ph PAuCl and HAuCl ·3H O, among them HAuCl ·3H O was found
3
4
2
4
2
to be best choice for this multicomponent reaction (MCRs) (Table 1,
Entry 11). On the basis of above observations, we choose gold(III)
chloride (HAuCl ·3H O) as a potential catalyst for the synthesis of
C25H23NO5 requires 417.1576).
4
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Ethyl
2 -Amino-2,5 -dioxo-5 ,6 ,7 ,8 -tetrahydro-2H-
spirooxindole derivatives under similar conditions.
ꢀ
ꢀ
spiro[acenaphthylene-1,4 -chromene]-3 -carboxylate
Yellow solid; mp: 224–226 C; IR (KBr): max = 3486, 3280, 2986,
1
4
J = 7.3 Hz, 2H, CH ), 2.30–2.31 (m, 2H, CH ) 1.35–1.37 (m, 2H,
CH ), 1.20–1.22 (m, 2H, CH ), 0.34 (t, J = 6.8 Hz, 3H, CH );
NMR (DMSO-d , 100 MHz): ı = 196.88, 195.41, 168.16, 165.43,
1
1
3
(7e):
A screening of solvents was also carried out under similar reac-
◦
ꢀ
tion conditions. There are several solvents such as C H5OH, CH CN,
2
3
−1 1
717, 1675, 1586, 1362, 1276, 1013, 755 cm
00 MHz): ı = 7.86–8.59 (m, 6H, ArH), 7.32 (s, 2H, NH ), 4.48 (q,
; HNMR (DMSO-d6,
H O, DMSO, DMF and PEGs were used and it turned out that PEG
2
2
4
00 was found to be a best choice as a solvent for this reaction with
2
2
excellent yield of product and less reaction time (Table 2, Entry 8).
PEG 400 is well known solvent which may increase the solubility
of the substrates and other reagents. Moreover, PEG 400 is able
to extract the hydrogen atom from active methylene groups (mal-
ononitrile or 1,3-dicarbonyl compounds) and is also able to retain
it by chelation through several lone pairs of electrons in its oxy-
gen containing chain. This may be due to the attraction between
the PEG hydroxyl group oxygen and hydrogen of the methylene
13
C
2
2
3
6
44.10, 132.30, 129.22, 128.62, 128.32, 128.16, 127.98, 124.34,
21.23, 116.11, 78.79, 62.41, 59.32, 39.70, 33.14, 27.84, 13.82; m/z
89.1263 (M + 1, C23H19NO5 requires 389.4007).
ꢀ
ꢀ
ꢀ
ꢀ
2
-Amino-2,5 -dioxo-2H,5 H-spiro[acenaphthylene-1,4 -
ꢀ
pyran[3,2-c]chromene]-3 -carbonitrile (7f): Brown solid; mp:
2
1
◦
ꢀ
55–256 C; IR (KBr): max = 3414, 3062, 2129, 1725, 1659,
(
CH ) of malononitrile. That makes the C–H bond weaker, enhanc-
2
−1
1
486, 1379, 1230, 1026 cm
;
H NMR (DMSO-d , 400 MHz):
6
ing the nucleophilicity of the carbon and the catalytic activity of
PEG 400 as a solvent was increased. Lower molecular weight PEG
ı = 8.32–8.39 (m, 2H, ArH), 8.13 (d, J = 7.3 Hz, 1H, ArH), 7.82–8.00
13
(m, 3H, ArH), 7.77 (br s, 2H, NH ), 7.42–7.66 (m, 4H); C NMR
2
2
00 was also tested as solvent, to give the low yield of product
(
DMSO-d , 100 MHz): ı = 195.35, 176.87, 158.49, 156.11, 152.24,
6
under same reaction conditions. These results showed that PEG
not only acted as recyclable solvent but could also accelerate the
three component reaction. In addition, when the reaction was per-
formed under solvent-free conditions to give only trace amount of
product (Table 2, Entry 6). The results show that the catalytic per-
formance is strongly affected by the type of solvent but a direct
correlation between solvent properties and their efficiency could
not be established in any case as summarized in Table 2.
1
1
5
42.11, 133.84, 132.34, 131.38, 129.97, 129.36, 128.87, 128.56,
27.85, 127.11, 126.43, 125.28, 123.75, 121.21, 117.26, 100.25,
7.75, 55.36; m/z 392.7026 (M + 1, C24H12N O requires 392.0797).
2
4
3
. Results and discussion
Initially, the synthesis of spirooxindole via one-pot three-
component reaction was carried out using 1 equiv. each of isatin,
malononitrile and dimedone as a model substrate (Scheme 1). The
reaction mixture was stirred at 70 C in PEG (5 mL). During the
The effect of temperature was also studied. The reaction was
carried out at different temperature, increasing from room tem-
perature to 80 C. We observed that the yield of product was
◦
◦
reaction, it was observed that the yield of product was 93% in the
improved and the reaction time was shortened as the tempera-
ture was increased from room temperature to 70 C. The product
◦
presence of 3 mol% of HAuCl ·3H O after 30 min (Table 1, Entry 10).
4
2
In contrast to this, the yield of product was very low in absence of
catalyst even after longer reaction time (Table 1, Entry 1).
yields plateaued when temperature was further increased up to
◦
◦
80 C (Table 2, Entry 10). Consequently, 70 C was found to be the
most suitable reaction temperature for an optimum yield of desired
product (Table 2, Entry 8).
The effect of catalyst loading for this transformation was also
studied. Interestingly, when increasing the amount of gold(III) chlo-
ride could improve the product yields significantly. Inspired by the
result, when we increased the concentration of catalyst from 3 mol%
to 10 mol%, increased the yield of product from 93% to 96%, respec-
tively (Table 1, Entries 10–12). It shows that using 5 mol% of gold(III)
chloride in PEG 400 is sufficient to push this reaction forward. More
amount of catalyst did not improve the product yields.
In order to prove that the use of polyethylene glycol as environ-
mentally benign solvent is also practical, it must be conveniently
recycled with minimum loss and decomposition. The reaction mix-
ture was cooled in dry ice-bath to precipitate the PEG 400 and
extracted with ether (PEG being insoluble in ether) and the retained
PEG phase may be reused. The recycled PEG does not change in its
reactivity but approximately 5% weight loss of PEG was observed
from cycle to cycle (Table 3). Therefore, we also examined the
To evaluate the catalytic activity of catalyst, the same reaction
was carried out in the presence of various Lewis acid catalysts

4
0
M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
H N
2
O
O
HAuCl .3H O
NC
4
2
(
5 mol%)
+
O
NC
CN
+
o
N
H
PEG 400, 70 C
O
O
N
H
4a
O
O
1
a
2a
3a
Scheme 1. HAuCl4·3H2O catalyzed Model reaction.
O
O
H N
2
O
O
X
3
a-c
R
N
O
HAuCl .3H O
4
2
R1 4a-n
O
O
(
5 mol%)
OH
R
+
NC
X
o
PEG 400, 70 C
H N
2
N
O
1a-d
R1
2a-b
O
X
O
3
d
R
O
N
O O
R1 5a-d
Scheme 2. HAuCl4·3H2O catalyzed one-pot three-component reaction of isatins, active methylene compounds and cyclic 1,3-diketones or 4-hydroxycoumarin.
H N
2
O
O
O
X
O
O
3
a-c
O
O
O
HAuCl .3H O
4
2
7
a-e
(
5 mol%)
OH
O
+
NC
X
o
H N
2
PEG 400, 70 C
2
a-b
O
X
O
6
3
d
O
O
7
f
Scheme 3. HAuCl4·3H2O catalyzed one-pot three-component reaction of acenaphthoquinone, active methylene compounds and cyclic 1,3-diketones or 4-hydroxycoumarin.
recyclability of the catalyst after the extraction of product with an
organic solvent (diethyl ether) was accompanied by considering
leaching of the catalyst, so the recyclability of the gold(III) chloride
is not possible.
5a–5d (Scheme 2 and Table 4). We used several types of isatins
including either electron withdrawing or electron donating groups,
malononitrile 2a or cyanoacetic ester 2b and cyclic 1,3-diketones
3a–3c or 4-hydroxycoumarin 3d were used in this reaction. It was
observed that all these cyclic 1,3-diketones or 4-hydroxycoumarin
as well as active methylene compounds were suitable for this reac-
tion which gives a satisfactory yield of desired products.
After optimization of reaction conditions, to delineate this
approach, especially in regard to library construction, this method-
ology was evaluated by using different isatins, active methylene
compounds and cyclic 1,3-diketones for the synthesis of a series
Encouraged by these remarkable results, further to extend this
protocol and in order to explore the scope of the HAuCl ·3H O cat-
ꢀ
of tetrahydrospiro[chromene-4,3 -indoline] derivatives 4a–4n and
4
2
alyst, we also examined one-pot three-component reaction using
another reactant acenaphthoquinone 6 inplace of isatins under
similar reaction conditions. We first used the optimized reaction
conditions of Entry 11, Table 1 and Entry 8, Table 2 to convert the
model reactant acenaphthoquinone 6, malononitrile 2a and dime-
done 3a in to the corresponding product spiro acenaphthyleneones
Table 3
Recyclability of PEG 400.
a
No. of cyclesa
Fresh
Run 1
Run 2
Run 3
Yield (%)b
Time (min)
96
30
94
30
93
30
90
30
7a. After apply the same reaction conditions, we were prepared a
variety of spiro acenaphthyleneone derivatives 7a–7f with excel-
lent yields (Scheme 3 and Table 5).
Mechanistically, we have proposed two plausible pathways [24]
for the synthesis of spirooxindole derivatives, Scheme 4 (path A and
a
Reaction conditions: isatin 1a (1 mmol), malononitrile 2a (1 mmol); dimedone
a (1 mmol), catalyst: gold(III) chloride (5 mol%); solvent: PEG 400 (5 mL); temper-
3
◦
ature: 70 C.
b
Isolated yields.

M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
41
Table 4
Synthesis of spirooxindole derivatives (4a–4n and 5a–5d).a
Entry
R
R1
Active methylene compounds
Cyclic 1,3-diketones/4-hydroxycoumarin
Product
Yield (%)b
O
CN
CN (2a)
CN
O
(3a)
1
H
H
4a
96
O
O
O
O
CN
CN
O
O
O
O
(3b)
2
3
H
H
H
H
4b
4c
94
92
O
O
CN
(3c)
O
O
O
O
CN
CN
CN
O
4
H
CH3
4d
93
CN
CN
5
6
H
H
CH3
CH3
4e
4f
94
90
O
O
O
O
CN
CN
CN
CN
O
7
H
COCH3
4g
91
CN
CN
8
9
H
H
COCH3
COCH3
4h
4i
88
83
O
CN
CN
CN
CN
O
1
0
5-Cl
H
4j
92
CN
CN
1
1
1
2
5-Cl
5-Cl
H
H
4k
4l
85
92
O
CN
CN
CN
O
1
3
H
H
4m
88

4
2
M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
Table 4 (Continued)
Entry
R
R1
Active methylene compounds
Cyclic 1,3-diketones/4-hydroxycoumarin
Product
Yield (%)b
O
CN
COOEt (2b)
O
1
1
1
1
4
5
6
7
8
H
H
4n
84
OH
CN
CN
O
O
O
O
O
(3d)
H
H
5a
5b
5c
5d
94
84
92
93
OH
CN
COOEt
O
H
H
OH
CN
CN
O
H
CH3
OH
CN
CN
O
1
5-Cl
H
a
Reaction conditions: isatins 1a–1d (1 mmol), active methylene compounds 2a and 2b (1 mmol); cyclic 1,3-diketones 3a–3c or 4-hydroxycoumarin 3d (1 mmol); catalyst:
◦
gold(III) chloride (5 mol%); solvent: PEG 400 (5 mL); temperature: 70 C.
b
Isolated yields.
CN
H
O
O
HAuCl4
HO
Cl AuH
4
NC H
CN
C
N
O
H
O
Cl AuH
H
O
2a
4
O
HAuCl4
Path A
O
3a
O
O
O
Path B
O
N
N
H
H
N
1a
H 10
Path B
HAuCl4
NC
HAu(H O)Cl
HAu(OH)Cl4
2
4
O
CN
O
HO
H
O
O
O
NC
NC
O
O
H
N
H
H
N
8
O
O
H 11
N
N
C
C
NC
NC
H
NC
O
HAu(OH)Cl4
O
NC
H
2a
O
O
N
N
NC
NC
H
H
9 H
HAu(H O)Cl
2
4
HN
NC
O
H N
O
2
NC
O
O
O
O
N
H
N
H 4a
Scheme 4. Plausible mechanism for the synthesis of spirooxindole 4a via path A and path B.

M. Kidwai et al. / Applied Catalysis A: General 425–426 (2012) 35–43
43
Table 5
Synthesis of spiro acenaphthyleneone derivatives (7a–7f).a
Appendix A. Supplementary data
Entry
Active methylene
compounds
Cyclic 1,3-diketones/4-
hydroxycoumarin
Product
Yield (%)b
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.apcata.2012.02.043.
1
2
3
4
5
6
2a
2a
2a
2b
2b
2a
3a
3b
3c
3a
3b
3d
7a
7b
7c
7d
7e
7f
91
76
85
82
88
90
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