Sonochemical multi-component synthesis of spirooxindoles

Article abstract of DOI:10.1016/j.ultsonch.2010.12.004

New and efficient multi-component methods have been developed for the synthesis of spirooxindoles in the presence of a catalytic amount of p-TSA as an inexpensive and available catalyst in EtOH under ultrasound irradiation. The method is simple, starts fr

Full text of DOI:10.1016/j.ultsonch.2010.12.004

Ultrasonics Sonochemistry 18 (2011) 1153–1159
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Sonochemical multi-component synthesis of spirooxindoles
⇑
⇑
Minoo Dabiri , Zeinab Noroozi Tisseh, Mahboobeh Bahramnejad, Ayoob Bazgir
Department of Chemistry, 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 3 October 2010
Received in revised form 8 December 2010
Accepted 12 December 2010
Available online 21 December 2010
New and efficient multi-component methods have been developed for the synthesis of spirooxindoles in
the presence of a catalytic amount of p-TSA as an inexpensive and available catalyst in EtOH under ultra-
sound irradiation. The method is simple, starts from readily accessible commercial starting materials, and
provides biologically interesting products in good yields and short reaction times.
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Multi-component reactions
Spirooxindole
Ultrasound
Isatin
Tetronic acid
1. Introduction
is fused to a heterocyclic systems attract specific attention. Some
derivatives of such polycyclic system showed anticancer [7], anti-
Ultrasonication, based on cavitation effects leading to mass
transfer improvement, is an important technique that is widely
used today in organic synthesis and has a profound impact on
the way chemists approach organic and parallel synthesis. Reduc-
tions in reaction times, improved yields and suppression of side
products, relative to traditional thermal heating, are benefits of this
technology [1]. A large number of organic reactions can be carried
out in higher yield, shorter reaction time and under milder condi-
tions, by using ultrasonic irradiation [2]. Also, multi-component
reactions (MCRs) are a very powerful tool for the construction of
complex organic molecules by using readily available starting
materials. MCRs have been frequently used by synthetic chemists
as a facile means to generate molecular diversity from bifunctional
substrates that react sequentially in an intramolecular fashion [3].
In this context, spirooxindoles show interesting features that make
them attractive for use in MCRs under ultrasound irradiation.
The indole moiety is probably the most well-known heterocy-
cle, a common and important feature of a variety of natural prod-
ucts and medicinal agents [4]. Furthermore, it has been reported
that sharing of the indole 3-carbon atom in the formation of spiro-
indoline derivatives can highly enhance biological activity [5]. The
spirooxindole system is the core structure of many pharmacologi-
cal agents and natural alkaloids [6].
rheumatic [8], antiarrythmic [9], and enzyme inhibitory activity
[10]. In the literature, there are a number of reliable methods for
the application of tetronic acid in the synthesis of biologically active
compounds [11].
As part of our continuing efforts on the synthesis of heterocyclic
compounds [12] and sonocatalysis organic transformations [13], we
have recentlyreported the sonocatalysis synthesis of spiro[indoline-
3,40-pyrazolo[3,4-b]pyridine]-2,60(10H)-dione derivatives [13c].
Although several isatin-based reactions have been reported in the
synthesis of spirooxindoles [14], the synthesis of spiro[benzo[g]-
furo[3,4-b]quinoline-indoline]-tetraones have not been reported
yet. In this paper, we report for the first time an efficient four com-
ponent sonocatalysis synthesis of spiro[benzo[g]furo[3,4-b]quino-
line-indoline]-tetraones.
2. Experimental
2.1. Chemicals and apparatus
The chemical used in this work were obtained from Fluka and
Merck and were used without purification. Melting points were
measured on an Electrothermal 9200 apparatus. IR spectra were
recorded on a FT-IR 102 MB BOMEM apparatus. Mass spectra
were recorded on a FINNIGAN-MAT 8430 mass spectrometer oper-
ating at an ionization potential of 70 eV. 1H and 13C NMR spectra
were recorded on a BRUKER DRX-300 AVANCE spectrometer at
300.13 and 75.47 MHz. 1H and 13C NMR spectra were obtained
on solutions in DMSO-d6 using TMS. Ultrasound assisted reactions
Tetronic acid (tetrahydrofuran-2,4-dione) is a promising conve-
nient building block and compoundsin whichtetronic acid fragment
⇑
Corresponding authors. Fax: +98 21 2403041.
E-mail address: a_bazgir@sbu.ac.ir (A. Bazgir).
1350-4177/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2010.12.004

1154
M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
were carried out using a EUROSONICÒ 4D ultrasound cleaner with
a frequency of 50 kHz and a nominal power of 350 W. The reac-
tions were carried out in an open glass tube (diameter: 20 mm;
thickness: 1 mm; volume: 25 mL) at 50 °C. The reaction flasks were
immersed in every place of the cleaner in such a way that the sur-
face of reactants is slightly lower than water in the cleaner, and the
temperature of the water bath can be controlled by an electronic
temperature control system.
2.6. 10-benzyl-1H-spiro[benzo[g]furo[3,4-b]quinoline-11,30-indoline]-
1,20,5,10(3H,4H)-tetraone (5e)
Dark yellow powder; mp: 128–130 °C. IR (KBr) (vmax cmꢁ1):
3436, 2926, 1731, 1666, 1355, 1284. MS, m/z (%): 474 (M+). 1H
NMR (300.13 MHz, DMSO-d6): dH 4.45 (2H, bs, CH2), 4.85 (2H, s,
CH2), 6.68–7.97 (13H, m, H–Ar), 11.51 (1H, s, NH). Anal. Calcd.
for C29H18N2O5: C, 73.41; H, 3.82; N, 5.90%. Found: C, 73.30; H,
3.90; N, 6.00% (Due to very low solubility of the product 5e, we
cannot report the 13C NMR data for this product).
2.2. Typical procedure for the preparation of 1H-
spiro[benzo[g]furo[3,4-b]quinoline-11,30-indoline]-1,20,5,10(3H,4H)-
tetraone (5a)
2.7. 10H,2H-spiro[acenaphthylene-1,110-benzo[g]furo[3,4-
b]quinoline10,2,50,100(30H,40H)-tetraone (9)
A mixture of isatin (1 mmol), tetronic acid (1 mmol), 2-hydro-
xy-1,4-naphthoquinone (1 mmol), ammonium acetate (1.5 mmol)
and p-TSA (20% mol) in EtOH (5 mL) was sonicated at 50 °C for
1.5 h. After completion of the reaction, the reaction mixture was
filtered and the precipitate washed with diethyl ether (2 ꢀ 5 mL)
to afford the pure product 5a as Orange powder; mp: 250–
252 °C. IR (KBr) (vmax cmꢁ1): 3457, 3272, 1734, 1680, 1607. MS,
m/z: 384 (M+). 1H NMR (300.13 MHz, DMSO-d6): dH 4.46 (2H, s,
CH2), 6.84–7.88 (8H, m, H–Ar), 10.45 (1H, s, NH), 10.64 (1H, s,
NH). 13C NMR (75.47 MHz, DMSO-d6): dC 51.3, 61.6, 109.1, 110.1,
121.2, 122.1, 125.1, 125.6, 125.8, 126.0, 126.8, 129.5, 130.2,
131.3, 131.5, 134.4, 143.1, 165.3, 175.1, 190.0. Anal. Calcd. for
Yellow powder; mp: 163–165 °C. IR (KBr) (vmax cmꢁ1): 3436,
2926, 1730, 1670, 1596, 1277. MS, m/z (%): 419 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.57 (2H, s, CH2), 7.17–8.54 (10H, m,
H–Ar), 11.46 (1H, s, NH). Anal. Calcd. for C26H13NO5: C, 74.46; H,
3.12; N, 3.34%. Found: C, 74.40; H, 3.18; N, 3.40% (Due to very
low solubility of the product 7, we cannot report the 13C NMR data
for this product).
2.8. 3,3-Bis(2,5-dihydro-4-hydroxy-2-oxofuran-3-yl)indolin-2-one
(10a)
Yellow powder; mp: 168–170 °C. IR (KBr) (vmax cmꢁ1): 3263,
3012, 1732, 1664, 1618. MS, m/z (%): 329 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.56 (4H, s, 2CH2), 6.73 (1H, d, H–Ar,
J = 7.6 Hz), 6.82 (1H, t, H–Ar, J = 7.5 Hz), 7.09 (1H, t, H–Ar,
J = 7.5 Hz), 7.28 (1H, d, H–Ar, J = 7.4 Hz), 10.48 (1H, s, NH), 11.88
(2H, bs, 2OH). 13C NMR (75.47 MHz, DMSO-d6): dC 47.9, 66.5,
96.9, 109.5, 121.6, 125.2, 128.1, 132.2, 142.1, 172.7, 173.8, 176.7.
Anal. Calcd. for C16H11NO7: C, 58.36; H, 3.37; N, 4.25%. Found: C,
58.25; H, 3.47; N, 4.36%.
C22H12N2O5: C, 68.75; H, 3.15; N, 7.29%. Found: C, 68.66; H, 3.22;
N, 7.38%.
2.3. 50-methyl-1H-spiro[benzo[g]furo[3,4-b]quinoline-11,30-indoline]-
1,20,5,10(3H,4H)-tetraone (5b)
Brown powder; mp: 167–168 °C. IR (KBr) (vmax cmꢁ1): 3193,
1740, 1679, 1639. MS, m/z (%): 398 (M+).1H NMR (300.13 MHz,
DMSO-d6): dH 1.99 (3H, s, CH3), 4.58 (2H, s, CH2), 6.86–8.00 (7H,
m, H–Ar), 10.42 (1H, s, NH), 10.92 (1H, s, NH). Anal. Calcd. for
2.9. 3,3-Bis(2,5-dihydro-4-hydroxy-2-oxofuran-3-yl)-5-
methylindolin-2-one (10b)
C
23H14N2O5: C, 69.34; H, 3.54; N, 7.03%. Found: C, 69.23; H, 3.42;
N, 7.12% (Due to very low solubility of the product 5b, we cannot
Yellow powder; mp: 163–165 °C. IR (KBr) (vmax cmꢁ1): 3430,
3054, 1732, 1669, 1612. MS, m/z (%): 343 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 2.27 (3H, s, CH3), 4.56 (4H, s, 2CH2),
6.63 (1H, d, H–Ar, J = 7.7 Hz), 6.90 (1H, d, H–Ar, J = 7.6 Hz), 7.12
(1H, s, H–Ar), 10.40 (1H, s, NH), 11.79 (2H, bs, 2OH). 13C NMR
(75.47 MHz, DMSO-d6): dC 21.3, 48.1, 66.5, 96.9, 109.2, 125.9,
128.4, 130.2, 132.2, 139.7, 172.7, 173.9, 176.8. Anal. Calcd. for
report the 13C NMR data for this product).
2.4. 50-bromo-1H-spiro[benzo[g]furo[3,4-b]quinoline-11,30-indoline]-
1,20,5,10(3H,4H)-tetraone (5c)
Yellow powder; mp: 162–163 °C. IR (KBr) (vmax cmꢁ1): 3449,
1715, 1620. MS, m/z (%): 463 (M+), 461 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.55 (2H, s, CH2), 6.76–7.98 (7H, m,
H–Ar), 10.88 (1H, s, NH), 11.44 (1H, s, NH). 13C NMR (75.47 MHz,
DMSO-d6): dC 50.5, 66.3, 98.4, 109.2, 121.5, 125.8, 125.9, 126.0,
126.4, 126.5, 128.2, 129.8, 131.2, 133.6, 134.0, 134.9, 135.2,
143.0, 171.9, 176.9, 181.3, 184.2. Anal. Calcd. for C22H11BrN2O5:
C, 57.04; H, 2.39; N, 6.05%. Found: C, 56.98; H, 2.45; N, 6.11%.
C17H13NO7: C, 59.48; H, 3.82; N, 4.08%. Found: C, 59.41; H, 3.89;
N, 4.15%.
2.10. 5-Bromo-3,3-bis(2,5-dihydro-4-hydroxy-2-oxofuran-3-
yl)indolin-2-one (10c)
Yellow powder; mp: 181–183 °C. IR (KBr) (vmax cmꢁ1): 3222,
3134, 1733, 1672, 1622. MS, m/z (%): 408 (M+), 406 (M+). 1H
NMR (300.13 MHz, DMSO-d6): dH 4.59 (4H, s, 2CH2), 6.71–7.49
(3H, m, H–Ar), 10.59 (1H, s, NH), 12.01 (2H, bs, 2OH). 13C NMR
(75.47 MHz, DMSO-d6): dC 47.9, 66.7, 99.3, 111.5, 125.9, 128.6,
130.8, 134.7, 138.4, 172.8, 174.1, 175.8. Anal. Calcd. for
2.5. 50-nitro-1H-spiro[benzo[g]furo[3,4-b]quinoline-11,30-indoline]-
1,20,5,10(3H,4H)-tetraone (5d)
C
16H10BrNO7: C, 47.08; H, 2.47; N, 3.43%. Found: C, 46.98; H,
Yellow powder; mp: 153–155 °C. IR (KBr) (vmax cmꢁ1): 3300,
1738, 1681, 1630, 1520, 1335. MS, m/z (%): 429 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.58 (2H, s, CH2), 7.78–8.16 (7H, m,
H–Ar), 10.96 (1H, s, NH), 11.16 (1H, s, NH). 13C NMR (75.47 MHz,
DMSO-d6): dC 50.1, 66.5, 97.1, 109.3, 120.5, 121.2, 125.9, 126.1,
126.4, 129.9, 132.3, 133.0, 132.3, 133.7, 135.2, 142.1, 149.7,
172.9, 177.0, 181.2. Anal. Calcd. for C22H11N3O7: C, 61.54; H,
2.58; N, 9.79%. Found: C, 61.50; H, 2.63; N, 9.85%.
2.56; N, 3.54%.
2.11. 3,3-Bis(2,5-dihydro-4-hydroxy-2-oxofuran-3-yl)-5-nitroindolin-
2-one (10d)
Yellow powder; mp: 178–180 °C. IR (KBr) (vmax cmꢁ1): 3255,
3067, 1733, 1667, 1617. MS, m/z (%): 374 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.61 (2H, s, CH2), 6.96 (1H, d, H–Ar,

M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
1155
J = 8.3 Hz), 8.11 (2H, d, H–Ar, J = 9.3 Hz), 11.14 (1H, s, NH), 12.45
2.17. 50-bromo-1-(4-bromophenyl)-10-ethyl-3-phenyl-7,8-
dihydrospiro[furo[3,4-b]pyrazolo [4,3-e]pyridine-4,30-indoline]-
20,5(1H)-dione (13d)
(2H, bs, 2OH). 13C NMR (75.47 MHz, DMSO-d6): dC 47.5, 66.9,
95.7, 109.6, 120.0, 125.8, 133.4, 142.2, 148.9, 172.8, 174.8, 176.3.
Anal. Calcd. for C16H10N2O9: C, 51.35; H, 2.69; N, 7.49%. Found: C,
51.31; H, 2.73; N, 7.53%.
Cream powder, m.p. > 300 °C; IR (KBr) (
1670; 1H NMR (DMSO-d6): dH 0.88 (3H, bs, CH3), 3.35 (2H, bs, CH2),
4.94 (2H, s, CH2), 6.78–7.76 (13H, m, Arom), 10.83 (1H, s, NH); 13
m
max, cmꢁ1): 3185, 1768,
C
2.12. 1-Benzyl-3,3-bis(2,5-dihydro-4-hydroxy-2-oxofuran-3-yl)
indolin-2-one (10e)
NMR (DMSO-d6): 12.4, 35.0, 52.3, 66.1, 99.6, 103.3, 111.7, 115.8,
124.3, 128.1, 128.3, 128.5, 130.0, 131.5, 132.9, 136.4, 137.0,
139.5, 142.8, 149.6, 159.6, 159.9, 160.8, 170.0, 175.8. MS (m/z)
632 (M+); Anal. Calcd for C29H20Br2N4O3: C, 55.09; H, 3.19; N,
8.86%. Found: C, 54.98; H, 3.24; N, 8.77%.
Yellow powder; mp: 168–170 °C. IR (KBr) (vmax cmꢁ1): 3390,
2923, 1716, 1671, 1610. MS, m/z (%): 419 (M+). 1H NMR
(300.13 MHz, DMSO-d6): dH 4.44 (4H, s, 2CH2), 4.96 (2H, s, CH2),
6.69–7.69 (9H, m, H–Ar), 8.19 (2H, bs, 2OH). Anal. Calcd. for
2.18. 1-(4-methoxyphenyl)-50-nitro-3-phenyl-7,8-dihydrospiro
[furo[3,4-b]pyrazolo[4,3-e]pyridine-4,30-indoline]-20,5(1H)-dione
(13e)
C23H17NO7: C, 65.87; H, 4.09; N, 3.34%. Found: C, 65.81; H, 4.26;
N, 3.41% (Due to very low solubility of the product 10e, we cannot
report the 13C NMR data for this product).
white powder, m.p. 275–277 °C; IR (KBr) (m
max, cmꢁ1): 3305,
3067, 1738, 1705; 1H NMR (DMSO-d6): dH 3.86 (3H, s, OCH3),
4.98 (2H, s, CH2), 6.65–8.47 (12H, m, Arom), 10.33 (1H, s, NH),
10.94 (1H, s, NH); 13C NMR (DMSO-d6): 47.5, 65.9, 99.1, 102.2,
109.8, 122.3, 124, 125.1, 125.6, 128.1, 128.3, 128.8, 129.1, 132.4,
135.7, 140, 142.1, 142.8, 146.2, 151.5, 159.3, 169.9, 177.9. Anal.
Calcd for C28H19N5O6: C, 64.49; H, 3.67; N, 13.43%. Found: C,
64.57; H, 3.60; N, 13.50%.
2.13. 3,30-(2-oxo-1,2- dihydroacenaphthylene-1,1-diyl)bis(4-hydroxy
furan-2(5H)-one) (11)
Yellow powder; mp: 188–190 °C. IR (KBr) (vmax cmꢁ1): 3244,
1736, 1673, 1618. MS, m/z (%): 364 (M+). 1H NMR (300.13 MHz,
DMSO-d6): dH 4.58 (4H, s, 2CH2), 7.11–7.61 (2H, m, H–Ar), 7.77
(1H, t, H–Ar, J = 7.7 Hz), 7.89 (2H, m, H–Ar), 8.21 (1H, d, H–Ar,
J = 7.9 Hz), 11.81 (2H, bs, 2OH). Anal. Calcd. for C20H12O7: C,
65.94; H, 3.32%. Found: C, 65.87; H, 3.39% (Due to very low solubil-
ity of the product 11, we cannot report the 13C NMR data for this
product).
2.19. 50-methyl-1,3-diphenyl-4,5-dihydrospiro[furo[3,4-e]
pyrazolo[4,3-b]pyridine-8,30-indoline]-20,7(1H)-dione (13f)
White powder, m.p. 279–281 °C; IR (KBr) (m
max, cmꢁ1): 3222,
3161, 1744, 1705; 1H NMR (DMSO-d6): dH 2.21 (3H, s, CH3), 4.93
(2H, s, CH2), 6.57–7.66 (13H, m, Arom), 10.21 (1H, s, NH), 10.71
(1H, s, NH); 13C NMR (DMSO-d6): 21.0, 47.7, 65.8, 98.8, 101.1,
109.5, 124.1, 125.5, 128.0, 128.3, 128.4, 129.2, 130.2, 131.2,
133.1, 136.2, 137.8, 139.5, 139.7, 149.8, 159.2, 170.1, 178. MS
(m/z) 460 (M+); Anal. Calcd for C28H20N4O3: C, 73.03; H, 4.38; N,
12.17%. Found: C, 72.92; H, 4.43; N, 12.06%.
2.14. 1,3-diphenyl-7,8-dihydrospiro[furo[3,4-b]pyrazolo[4,3-e]
pyridine-4,30-indoline]-20,5(1H)-dione (13a)
Yellow powder, m.p. 258–261 °C; IR (KBr) (m
max, cmꢁ1): 3383,
3205, 1721; 1669; 1H NMR (DMSO-d6): dH 4.98 (2H, s, CH2),
6.81–8.32 (14H, m, Arom), 10.94 (1H, s, NH), 11.07 (1H, s, NH);
13C NMR (DMSO-d6): 46.9, 66.4, 96.1, 96.7, 100.3, 108.8, 120.3,
124.3, 126.3, 128.2, 128.4, 128.6, 130.1, 132.4, 135.4, 137.6,
139.5, 143.4, 149, 149.8, 160.6, 170.2, 177.4. MS (m/z) 446 (M+);
Anal. Calcd for C27H18N4O3: C, 72.64; H, 4.06; N, 12.55%. Found:
C, 72.58; H, 4.01; N, 12.49%.
2.20. 1,3-diphenylspiro[benzo[g]pyrazolo[3,4-b]quinoline-4,30-
indoline]-20,5,10(1H,11H)-trione (15a)
Red powder, m.p. 268–270 °C; IR (KBr) (m
max, cmꢁ1): 3426,
3343, 1755, 1727, 1678; 1H NMR (DMSO-d6): dH 6.61–8.57 (18H,
m, Arom), 10.46 (1H, s, NH), 11.47 (1H, s, NH); 13C NMR (DMSO-
d6): 51.4, 105.6, 109.9, 114.8, 120.9, 122.5, 123.3, 124.0, 125.9,
126.2, 127.5, 128.0, 128.6, 128.9, 129.5, 129.7, 131.8, 132.7,
133.2, 134.3, 134.7, 138.8, 143.9, 149.2, 152.4, 153.5, 176.3,
179.3, 181.0. MS (m/z) 520 (M+); Anal. Calcd for C33H20N4O3: C,
76.14; H, 3.87; N, 10.76% Found: C, 76.07; H, 3.81; N, 10.68.
2.15. 1-(4-nitrophenyl)-3-phenyl-7,8-dihydrospiro[furo[3,4-b]
pyrazolo[4,3-e]pyridine-4,30-indoline]-20,5(1H)-dione (13b)
White powder, m.p. 270–272 °C; IR (KBr) (m
max, cmꢁ1): 3383,
3077, 1755, 1700; 1H NMR (DMSO-d6): dH 4.94 (2H, s, CH2),
6.60–8.32 (13H, m, Arom), 10.47 (1H, s, NH), 10.81 (1H, s, NH).
MS (m/z) 491 (M+); Anal. Calcd for C27H17N5O5: C, 65.99; H, 3.49;
N, 14.25%. Found: C, 65.90; H, 3.42; N, 14.17% (Due to very low sol-
ubility of the product 13b, we cannot report the 13C NMR data for
this product).
2.21. 1-(4-methoxyphenyl)-3-phenylspiro[benzo[g]pyrazolo[3,4-b]
quinoline-4,30-indoline]-20,5,10(1H,11H)-trione (15b)
Dark red powder, m.p. 260–262 °C; IR (KBr) (m
max, cmꢁ1): 3343,
3200, 1745, 1650, 1615; 1H NMR (DMSO-d6): dH .3.86 (1H, s, OCH3),
6.66–8.07 (17H, m, Arom), 9.90 (1H, s, NH), 10.09 (1H, s, NH); MS
(m/z) 550 (M+); Anal. Calcd for C34H22N4O4: C, 74.17; H, 4.03; N,
10.18% Found: C, 74.06; H, 4.08; N, 10.24 (Due to very low solubil-
ity of the product 15b, we can not report the 13C NMR data for this
product).
2.16. 50-bromo-10-ethyl-1,3-diphdihydrospiro[furo[3,4-b]
pyrazolo[4,3-e]pyridine-4,30-indoline]-20,5(1H)-dione (13c)
Cream powder, m.p. > 300 °C; IR (KBr) (m
max, cmꢁ1): 3179, 1763,
1669; 1H NMR (DMSO-d6): dH 0.82 (3H, s, CH3), 3.32 (2H, s, CH2),
4.93 (2H, s, CH2), 6.75–7.66 (13H, m, Arom), 10.79 (1H, s, NH);
13C NMR (DMSO-d6): 12.1, 34.7, 52.1, 66.1, 99.3, 100.3, 110.7,
114.6, 124.2, 127.8, 128.2, 128.5, 130.1, 131.8, 132.8, 137.4,
137.7, 139.6, 141.9, 149.7, 158.8, 159.1, 160.5, 170, 175.6. MS
(m/z) 554 (M+), 552 (M+); Anal. Calcd for C29H21BrN4O3: C, 62.94;
H, 3.82; N, 10.12%. Found: C, 62.86; H, 3.88; N, 10.04%.
2.22. 1-(4-nitrophenyl)-3-phenylspiro[benzo[g]pyrazolo[3,4-b]
quinoline-4,30-indoline]-20,5,10(1H,11H)-trione (15c)
Red powder, m.p. > 300 °C; IR (KBr) (
1715, 1676, 1644; 1H NMR (DMSO-d6): dH 8.57–8.86 (17H, m,
m
max, cmꢁ1): 3210, 3061,

1156
M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
Arom), 10.05 (1H, s, NH), 10.18 (1H, s, NH); 13C NMR (DMSO-d6):
50.6, 101.0, 101.2, 111.4, 113.5, 118.0, 123.8, 125.2, 126.4, 126.8,
127.3, 127.9, 128.0, 128.2, 128.6, 129, 130.0, 130.3, 131.2, 133.8,
135.7, 136.9, 138.5, 140.3, 141.7, 178.9, 181.0. MS (m/z) 565
(M+); Anal. Calcd for C33H19N5O5: C, 70.08; H, 3.39; N, 12.38%
Found: C, 70.02; H, 3.34; N, 12.30.2.2.3.
3. Results and discussion
In a pilot experiment, a mixture of isatin 1a, teronic acid 2,
2-hydroxy-1,4-naphthoquinone 3 and ammonium acetate 4 in
the presence of a catalytic amount of p-TSA was sonicated at
50 °C for 1.5 h. After completion of the reaction (monitored by
TLC), the crude product was separated from the reaction mixture
by filtration and washed with diethyl ether (2 ꢀ 5 mL) to afford
product 5a in 90% yield (Scheme 1).
2.23. 50-bromo-10-ethyl-1,3-diphenylspiro[benzo[g]pyrazolo[3,4-b]
quinoline-4,30-indoline]-20,5,10(1H,11H)-trione (15d)
To search for the optimal reaction solvent, this reaction was
examined in H2O, CH2Cl2, CH3CN and EtOH at 50 °C under ultra-
sonic irradiation. As shown in Table 1, the reaction using ethanol
as solvent resulted in higher yields and short reaction time (Table
1, entry 3). To study the effect of amount of the catalyst, the reac-
tions were carried out at different amount of p-TSA ranging from
10–30 mol%. It was found that when increasing the amount of
the p-TSA from 10 to 20, and 30 mol%, the yields increased from
71 to 90 and 91%, respectively (Table 1, entries 2–4). It was found
that 20 mol% p-TSA in ethanol is sufficient to push this reaction for-
ward (Table 1, entry 3). More amounts of the additive did not im-
prove the yields. When this reaction was carried out without p-TSA
the yield of the expected product was very low (Table 1, Entry 1).
To optimize the reaction temperature, we also performed several
experiments at 25, 35, 40 and 50 °C under ultrasonic irradiation.
It was found that the most suitable reaction temperature is 50 °C
under ultrasonic irradiation (Entry 3). The effect of ultrasound irra-
diation on the reaction was also observed. As shown in Table 1, un-
der silent condition by using stirring for 6 h, the model reaction
gave 5a in <30% yield (Table 1, Entry 11). In was found that the
use of ultrasound irradiation leads to a higher yield in shorter reac-
tion time.
Red powder, m.p. 269–271 °C; IR (KBr) (m
max, cmꢁ1): 3255, 1722,
1705, 1677; H NMR (DMSO-d6): dH 0.83 (3H, bs, CH3), 3.15 (2H, bs,
CH2), 6.63–8.05 (17H, m, Arom), 9.98 (1H, s, NH); 13C NMR (DMSO-
d6): 11.8, 34.7, 50.0, 110.4, 123.8, 126.5, 127.4, 128.0, 128.2, 128.6,
128.9, 130.0, 130.4, 131.4, 132.2, 132.6, 133.0, 133.8, 135.6, 138.5,
139.5, 142.2, 143.0, 149.7, 151.0, 152.6, 178.9, 181.0. MS (m/z) 628
(M+), 626 (M+); Anal. Calcd for C35H23BrN4O3: C, 66.99; H, 3.69; N,
8.93% Found: C, 66.90; H, 3.74; N, 9.01.
2.24. 50-nitro-1,3-diphenylspiro[benzo[g]pyrazolo[3,4-b]quinoline-
4,30-indoline]-20,5,10(1H,11H)-trione (15e)
Dark red powder, m.p. 271–273 °C; IR (KBr) (m
max, cmꢁ1): 3426,
3327, 1705, 1672, 1650; 1H NMR (DMSO-d6): dH 6.68–8.52 (17H, m,
Arom), 10.84 (1H, s, NH), 11.16 (1H, s, NH); 13C NMR (DMSO-d6):
51.3, 83.2, 97.8, 108.9, 117.2, 118.5, 120.1, 121.3, 122.2, 124.1,
126.5, 126.8, 128.5, 129.9, 131.9, 133.2, 134.2, 135.9, 136.0,
143.5, 146.4, 150.7, 151.5, 152.4, 157.2, 160.2, 179.4, 181.7. MS
(m/z) 565 (M+); Anal. Calcd for C33H19N5O5: C, 70.08; H, 3.39; N,
12.38% Found: C, 70.13; H, 3.32; N, 12.31.
Then, to delineate this approach, particularly in regard to library
construction, this methodology was evaluated by using different
isatins 1a–e. Corresponding spiro[benzo[g]furo[3,4-b]quinoline-
11,30-indoline]-tetraones 5a–e were selectively synthesized by
the four-component condensation of isatins 1, teronic acid 2, 2-hy-
droxy-1,4-naphthoquinone 3 and ammonium acetate 4 in good
yields under ultrasound irradiation at 50 °C in the presence of
2.25. 50-nitro-1-(4-nitrophenyl)-3-phenylspiro[benzo[g]pyrazolo[3,4-
b]quinoline-4,30-indoline]-20,5,10(1H,11H)-trione (15f)
Dark red powder, m.p. > 300 °C; IR (KBr) (m
max, cmꢁ1): 3418,
3329, 1711, 1670, 1653; 1H NMR (DMSO-d6): dH 6.49–8.58 (16H,
m, Arom), 10.28 (1H, s, NH), 10.59 (1H, s, NH); MS (m/z) 610
(M+); Anal. Calcd for C33H18N6O7: C, 64.92; H, 2.97; N, 13.77%
Found: C, 64.84; H, 2.93; N, 13.85 (Due to very low solubility of
the product 15f, we can not report the 13C NMR data for this
product).
Table 1
Optimization of conditionsa.
Entry
Conditions
p-TSA (mol%)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
EtOH/50 °C/ultrasound
EtOH/50 °C/ultrasound
EtOH/50 °C/ultrasound
EtOH/50 °C/ultrasound
EtOH/40 °C/ultrasound
EtOH/35 °C/ultrasound
EtOH/25 °C/ultrasound
H2O/50 °C/ultrasound
CH2Cl2/50 °C/ultrasound
CH3CN/50 °C/ultrasound
EtOH/50 °C/Silent
None
10
20
30
20
20
20
20
20
20
20
5
3
<30
71
90
91
78
63
55
<30
45
55
2.26. 50-methyl-1,3-diphenylspiro[benzo[g]pyrazolo[3,4-b]quinoline-
1.5
1.5
1.5
1.5
1.5
5
5
5
6
4,30-indoline]-20,5,10(1H,11H)-trione (15g)
Red powder, m.p. > 300 °C; IR (KBr) (m
max, cmꢁ1): 3194, 3056,
1716, 1678; 1H NMR (DMSO-d6): 2.17 (3H, S, CH3), 6.49–8.05
(17H, m, Arom), 10.02 (1H, s, NH), 10.07 (1H, s, NH); MS (m/z)
534 (M+); Anal. Calcd for C34H22N4O3: C, 76.39; H, 4.15; N,
10.48% Found: C, 76.30; H, 4.21; N, 10.53 (Due to very low solubil-
ity of the product 15g, we can not report the 13C NMR data for this
product).
10
11
<30
a
Isatin 1a (1 mmol), teronic acid 2 (1 mmol), 2-hydroxy-1,4-naphthoquinone 3
(1 mmol), and ammonium acetate 4 (1.5 mmol).
O
H
EtOH/ 50 oC
O
O
N
O
OH
))))))
O
O
O
NH4OAc
O
N
O
O
O
H
p-TSA (20% mol)
1.5h
O
N
H
1a
2
3
4
5a
Scheme 1.

M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
1157
Table 2
Synthesis of spiro[benzofuroquinoline-indoline]-tetraone 5.
O
H
N
O
O
EtOH/ 50 o
))))))
C
O
X
OH
O
O
O
NH4OAc
N
O
p-TSA (20% mol)
O
X
R
O
O
O
N
R
1a-e
2
3
4
5a-e
Entry
X
R
Ultrasound time (h)/yield (%)
Conventional heating yield (%)a
a
b
c
H
Me
Br
H
H
H
1.5/90
1.5/87
2/89
<30
<30
<30
d
e
NO2
H
H
CH2Ph
2/78
1.5/73
Trace
Trace
a
Reaction time = 4 h, 50 °C in EtOH, p-TSA (20% mol).
O
O
O
O
OH
HO
HO
H
O
O
O
N
O
O
H
H N
2
OH
O
N
H
H
1
3
O
5
6
- H2O
- H2O
O
O
O
NH
O
H
NH4OAc
O
O
H2N
2
7
Scheme 2.
O
H
N
O
O
O
EtOH/ 50 oC
))))))
O
O
O
O
OH
O
NH4OAC
O
O
p-TSA (20% mol)
1.5h
O
90%
8
3
4
2
9
Scheme 3.
Table 3
Synthesis of oxindoles 10.
OH
OH
O
O
EtOH/ 50 oC
O
O
O
O
O
X
))))))
X
2
O
O
N
p-TSA (20% mol)
R
O
N
R
1 h
1
X
2
10a-e
Entry
R
Time (h)
Yield (%)
a
b
c
d
e
H
Me
Br
NO2
H
H
H
H
H
1
1.5
2
1
2
93
91
83
80
81
CH2Ph

1158
M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
p-TSA for 1.5–2 h. The reaction can be represented as in Table 2. On
the other hand, when comparing the results obtained using con-
ventional heating with ultrasound-assisted method, we can con-
clude that the main advantages of ultrasound are the significant
decrease of reaction times and improvement of yields (Table 2).
To the best of our knowledge, this new procedure provides the
first example of an efficient method for the synthesis of spiro[ben-
zo[g]furo[3,4-b]quinoline-11,30-indoline]-tetraones. This method,
based on four-component p-TSA-catalyzed reaction under ultra-
sonic irradiation, is the most simple and convenient and would
be applicable for the synthesis of different types of spiro[benzof-
uroquinoline-indoline]-tetraones. Moreover, it is worth noting that
two C–C and two C–N bonds were formed with concomitant
creation of a spirooxindole fused benzofuroquinoline in this one-
pot, four-component process.
We have not established a detailed mechanism for the forma-
tion of 5, however, a reasonable possibility is shown in Scheme
2. The formation of products 5 can be rationalized by initial forma-
tion of intermediate 6 via condensation of 1 and 3. Subsequent
addition of enamine 7 (formed in situ by reaction of 2 with ammo-
nium acetate), to the intermediate 6 followed by cyclization affor-
ded product 5 (Scheme 2).
As expected, when the isatin 1 was replaced by acenaphthyl-
ene-1,2-dione 8 (Scheme 3), spiro[acenaphthylene-benzo[g]furo-
quinoline] 9 was obtained in 90% yield under the same reaction
conditions.
During our investigation on the synthesis of spirooxindole fused
benzofuroquinolines, we found that in the absence of ammonium
acetate and 2-hydroxy-1,4-naphthoquinone 3, isatins 1 and tetron-
ic acid 2 using similar conditions gave 3,30-(2-oxoindoline-3,3-
diyl)bis(4-hydroxyfuran-2(5H)-one) derivatives 10a–f in 78–93%
yields (Table 3). Reaction of acenaphthylene-1,2-dione 6 with
tetronic acid 2 resulted in the formation of 3,30-(2-oxo-1,2-
dihydroacenaphthylene-1,1-diyl)bis(4-hydroxyfuran-2(5H)-one)
11 in 91% yield (Scheme 4).
OH
OH
O
O
O
EtOH/ 50 o
))))))
C
O
O
O
O
2
O
O
O
p-TSA (20% mol)
1h
91%
8
2
11
To further explore the potential of this protocol for spirooxindole
synthesis, we investigated the three-component reaction of
Scheme 4.
Table 4
Synthesis of spirooxindoles 13.
H
Ph
N
O
O
O
O
Ph
EtOH/ 50 o
))))))
C
N
X
N
O
O
O
N
X
NH2
N
Ar
N
O
p-TSA (20% mol)
R
Ar
N
R
1
2
12
13
Product 9
Ar
X
R
Time (h)
Yield (%)
a
b
c
d
e
f
C6H5
4-NO2–C6H4
C6H5
4-Br–C6H4
4-MeO–C6H4
C6H5
H
H
Br
Br
NO2
Me
H
H
Et
Et
H
H
3
91
92
83
79
84
83
2.5
4.5
4
4
3.5
Table 5
Synthesis of spirooxindoles 15.
O
H
N
O
EtOH/ 50 o
))))))
C
O
Ph
Ph
OH
X
O
N
N
O
NH2
N
Ar
N
Ar
X
N
R
p-TSA (20% mol)
O
O
N
R
14
Ar
10
1
15
Product 13
X
R
Time (h)
Yield (%)
a
b
c
d
e
f
C6H5
H
H
H
Br
NO2
NO2
Me
H
H
H
Et
H
H
H
2
2.5
2
2.5
1.5
2
91
85
92
83
84
80
82
4-MeO–C6H4
4-NO2–C6H4
C6H5
C6H4
4-NO2–C6H4
C6H5
g
3

M. Dabiri et al. / Ultrasonics Sonochemistry 18 (2011) 1153–1159
1159
[8] B. Atsuo, O. Tsuneo, T. Shigehisa, N. Kohei, N. Atsushi, M. Haruhiko, S. Takashi,
Studies on disease-modifying antirheumatic drugs. III. Bone resorption
inhibitory effects of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-
triazol-1-ylmethyl)quinoline-3-carboxylate (TAK-603) and related compounds,
Chem. Pharm. Bull. 47 (1999) 369.
[9] I.P. Skrastin’sh, R.O. Vitolin’ya, V.V. Kastron, G.M. Avakumova, G.Y. Dubur,
Cardiovascular activity of difuropyridines, Pharm. Chem. J. 26 (1992) 416.
[10] A. Iida, M. Kano, Y. Kubota, K. Koga, K. Tomioka, Targeting DNA topoisomerase
II with podophyllotoxin aza-analogue, Bioorg. Med. Chem. Lett. 20 (1997)
2565.
pyrazoles-5-amines 12 and isatins 1 with teronic acid 2 and ob-
tained
spiro[furo[3,4-b]pyrazolo[4,3-e]pyridine-4,30-indoline]-
diones 13 in good yields under the same reaction conditions (Table
4).
When the 2-hydroxy-1,4-naphthoquinone 14 was selected as
active b-dicarbonyl compounds in the three-component reaction
(Table 5), the desired spiro[benzo[g]pyrazolo[3,4-b]quinoline-
11,30-indoline]-20,5,10(1H,4H)-triones 15 were obtained in good
yields.
[11] (a) J.P. Hehn, D. Gamba-Sánchez, M. Kemmler, M. Fleck, B. Basler, T. Bach,
[2+2]-Photocycloaddition reactions of tetronic acid esters and amides,
Synthesis (2010) 2308;
(b) Y. Bourdreux, E. Bodio, C. Willis, C. Billaud, T.L. Gall, C. Mioskowski,
Synthesis of vulpinic and pulvinic acids from tetronic acid, Tetrahedron 64
(2008) 8930;
4. Conclusion
(c) N.G. Kozlov, S.L. Bondarev, A.P. Kadutskii, L.I. Basalaeva, F.S. Pashkovskii,
Tetronic acid in reaction with aromatic aldehydes 2-naphthylamine.
Investigation of fluorescent nonlinear-optical characteristics of compounds
obtained, Russ. J. Org. Chem. 44 (2008) 1031;
In conclusion, we have developed one-pot and efficient multi-
component procedures for a convenient and mild synthesis of var-
ious spirooxindoles. Prominent among the advantages of these
new methods are operational simplicity, good yields in short reac-
tion times and easy work-up procedures employed.
(d) A.P. Kadutskii, N.G. Kozlov, F.S. Pashkovskii, Synthesis of benzo[f]quinoline
derivatives by three-component condensation of tetronic acid with
naphthalen-2-amine and formaldehyde, Russ. J. Org. Chem. 45 (2009) 399;
(e) A. Shaabani, E. Soleimani, A. Sarvary, A.H. Rezayan, A simple and efficient
approach to the synthesis of 4H-furo[3,4-b]pyrans via a three-component
reaction of isocyanides, Bioorg. Med. Chem. Lett. 18 (2008) 3968;
(f) A. Shaabani, A. Sarvary, S. Keshipour, A.H. Rezayan, R. Ghadari, Unexpected
Knoevenagel self-condensation reaction of tetronic acid: Synthesis of a new
class of organic heterocyclic salts, Tetrahedron 66 (2010) 1911.
[12] (a) R. Ghahremanzadeh, T. Amanpour, A. Bazgir, Pseudo four-component
synthesis of benzopyranopyrimidines, Tetrahedron Lett. 51 (2010) 4202;
(b) R. Ghahremanzadeh, S. Ahadi, G. Imani Shakibaei, A. Bazgir, Grindstone
chemistry: One-pot synthesis of spiro[diindenopyridine-indoline triones and
spiro[acenaphthylene-diindenopyridine]triones, Tetrahedron Lett. 51 (2010)
499;
References
[1] (a) G. Cravotto, P. Cintas, Power ultrasound in organic synthesis: Moving
cavitational chemistry from academia to innovative and large-scale
applications, Chem. Soc. Rev. 35 (2006) 180;
(b) T.J. Mason, J.P. Lorimer, Applied Sonochemistry, The Uses of Power
Ultrasound in Chemistry and Processing, Wiley VCH, Verlag GmbH, 2002.
[2] (a) M. Nikpassand, M. Mamaghani, F. Shirini, Kh. Tabatabaeian, A convenient
ultrasound-promoted regioselective synthesis of fused polycyclic 4-aryl-3-
methyl-4,7-dihdro-1H-pyrazolo[3,4-b]pyridines, Ultrason. Sonochem. 17
(2010) 301;
(c) R. Ghahremanzadeh, G. Imani Shakibaei, S. Ahadi, A. Bazgir, One-pot,
pseudo four-component synthesis of a spiro[diindeno[1,2-b:20,10-e]pyridine-
11,30-indoline]-trione library, J. Comb. Chem. 12 (2010) 191;
(d) G. Imani Shakibaei, S. Samadi, R. Ghahremanzadeh, A. Bazgir, Simple and
catalyst-free synthesis of oxoindolin-3-yl phosphonates, J. Comb. Chem. 12
(2010) 295.
(b) T.J. Mason, Sonochemistry and the environment – Providing a ‘‘green’’ link
between chemistry, physics and engineering, Ultrason. Sonochem. 14 (2007)
476;
(c) E. Kimmel, Cavitation bioeffects, Crit. Rev. Biomed. Eng. 34 (2006) 05;
(d) N.M.A. Rahman, T.S. Saleh, M.F. Mady, Ultrasound assisted synthesis of
some new 1,3,4-thiadiazole and bi(1,3,4-thiadiazole) derivatives incorporating
pyrazolone moiety, Ultrason. Sonochem. 16 (2009) 70;
(e) E.K. Goharshadi, Y. Ding, N.M. Jorabachi, P. Nancarrow, Ultrasound-assisted
green synthesis of nanocrystalline ZnO in the ionic liquid [hmim][NTf2],
Ultrason. Sonochem. 16 (2009) 120;
(f) J.L. Luche, Synthetic Organic Sonochemistry, Plenum, New York, 1998 (and
the references cited therein).
[13] (a) M.
R Nabid, S.J. Tabatabaei Rezaei, R. Ghahremanzadeh, A. Bazgir,
Ultrasound-assisted one-pot, three-component synthesis of 1H-pyrazolo[1,2-
b]phthalazine-5,10-diones, Ultrason. Sonochem. 17 (2010) 159;
(b) A. Rajabi Khorami, F. Faraji, A. Bazgir, Ultrasound-assisted three-component
synthesis of 3-(5-amino-1H-pyrazol-4-yl)-3-(2-hydroxy-4,4-dimethyl-6-oxocy-
clohex-1-en yl)indolin-2-ones in water, Ultrason. Sonochem. 17 (2010) 587;
(c) R. Ghahremanzadeh, F. Fereshtehnejad, P. Mirzaei, A. Bazgir, Ultrasound-
assisted synthesis of 2,20-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione)
derivatives, Ultrason. Sonochem. 18 (2011) 415;
[3] (a) A. Dömling, I. Ugi, Multicomponent reactions with isocyanides, Angew.
Chem. Int. Edit. 39 (2000) 3168;
(d) A. Bazgir, S. Ahadi, R. Ghahremanzadeh, H.R. Khavasi, P. Mirzaei, Ultrasound-
assistedone-pot, three-componentsynthesisofspiro[indoline-3,40-pyrazolo[3,4-
b]pyridine]-2,60(10H)-diones in water, Ultrason. Sonochem. 17 (2010) 447.
[14] (a) S.-L. Zhu, S.-J. Jia, Y. Zhang, A simple and clean procedure for three-
component synthesis of spirooxindoles in aqueous medium, Tetrahedron 63
(2007) 9365;
(b) A. Dömling, Recent developments in isocyanide based multicomponent
reactions in applied chemistry, Chem. Rev. 106 (2006) 17;
(c) C.I. Herrerias, X. Yao, Z. Li, C. Li, Reactions of C–H bonds in water, Chem.
Rev. 107 (2007) 2546.
[4] R.J. Sundberg, The Chemistry of Indoles, Academic, New York, NY, 1996.
[5] (a) K.C. Joshi, P. Chand, Biologically active indole derivatives, Pharmazie 37
(1982);
(b) R.S. Kumar, S. Perumal, Novel three-component tandem reactions of cyclic
mono ketones, isatin and sarcosine: Formation of dispiropyrrolidines,
Tetrahedron Lett. 48 (2007) 7164;
[b] J.F.M. Da-Silva, S.J. Garden, A.C. Pinto, The chemistry of isatins: A review
from 1975 to 1999, J. Braz. Chem. Soc. 12 (2001) 273;
(c) R.Gr. Redkin, L.A. Shemchuk, V.P. Chernykh, O.V. Shishkin, S.V. Shishkina,
Synthesis and molecular structure of spirocyclic 2-oxindole derivatives of 2-
amino-4H-pyran condensed with the pyrazolic nucleus, Tetrahedron 63
(2007) 11444;
(c) A.H. Abdel-Rahman, E.M. Keshk, M.A. Hanna, Sh.M. El-Bady, Synthesis and
evaluation of some new spiro indoline-based heterocycles as potentially active
antimicrobial agents, Bioorg. Med. Chem. 12 (2006) 2483;
(d) S.-L. Zhu, S.-J. Ji, Z. Yong,
A simple and clean procedure for three-
(d) G. Shanthi, G. Subbulakshmi, P.T. Perumal, A new InCl3-catalyzed, facile
and efficient method for the synthesis of spirooxindoles under conventional
and solvent-free microwave conditions, Tetrahedron 63 (2007) 2057;
(e) A.A. Esmaeili, M. Darbanian, Reaction between alkyl isocyanides and
dialkyl acetylenedicarboxylates in the presence of N-alkyl isatins: Convenient
component synthesis of spirooxindoles in aqueous medium, Tetrahedron 63
(2007) 9365.
[6] (a) T.-H. Kang, K. Matsumoto, Y. Murakami, H. Takayama, M. Kitajima, N. Aimi,
H. Watanabe, Pteropodine and isopteropodine positively modulate the
function of rat muscarinic M1 and 5-HT2 receptors expressed in Xenopus
oocyte, Eur. J. Pharmacol. 444 (2002) 39;
synthesis of c-spiro-iminolactones, Tetrahedron 59 (2003) 5545;
(f) A.A. Mohammadi, M. Dabiri, H. Qaraat, A regioselective three-component
reaction for synthesis of novel 10H-spiro[isoindoline-1,20-quinazoline]-
3,40(30H)-dione derivatives, Tetrahedron 65 (2009) 3804;
(g) A.H. Abdel-Rahman, E.M. Keshk, M.A. Hanna, Sh.M. El-Bady, Synthesis and
evaluation of some new spiro indoline-based heterocycles as potentially active
antimicrobial agents, Bioorg. Med. Chem. 12 (2004) 2483;
(h) L.-M. Wang, N. Jiao, J. Qiu, J.-J. Yu, J.-G. Liu, F.-L. Guo, Y. Liu, Sodium
stearate-catalyzed multicomponent reactions for efficient synthesis of
spirooxindoles in aqueous micellar media, Tetrahedron 66 (2010) 339.
(b) J. Ma, S.M. Hecht, Javaniside, a novel DNA cleavage agent from Alangium
javanicum having an unusual oxindole skeleton, Chem. Commun. (2004) 1190;
(c) T. Usui, M. Kondoh, C.-B. Cui, T. Mayumi, H. Osada, Tryprostatin A, a specific
and novel inhibitor of microtubule assembly, Biochem. J. 333 (1998) 543;
(d) M.M. Khafagy, A.H.F.A. El-Wahas, F.A. Eid, A.M. El-Agrody, Synthesis of
halogen derivatives of benzo[h]chromene and benzo[a]anthracene with
promising antimicrobial activities, Farmaco 57 (2002) 715.
[7] L. Jurd, New anti-tumor agents. 1. Heterocyclic benzodioxole lactones, J.
Heterocycl. Chem. 33 (1996) 1227.