An efficient synthesis of fluorescent spiro[benzopyrazoloquinoline- indoline]triones and spiro[acenaphthylenebenzopyrazolo-quinoline]triones

Article abstract of DOI:10.1007/s00706-011-0571-x

An efficient and simple synthesis of spiro[11H-benzo[g]pyrazolo[4,3-b] quinoline-11,3′-[3H]indole]-2′,5,-10(1′H)-triones and spiro[acenaphthylene-1(2H),11′-[11H]-benzo[g]pyrazolo[4,3-b]quinoline]-2, 5′,10′-triones by a three-component condensation reactio

Full text of DOI:10.1007/s00706-011-0571-x

Monatsh Chem (2012) 143:139–143
DOI 10.1007/s00706-011-0571-x
ORIGINAL PAPER
An efficient synthesis of fluorescent spiro[benzopyrazoloquinoline-
indoline]triones and spiro[acenaphthylenebenzopyrazolo-
quinoline]triones
•
Minoo Dabiri Zeinab Noroozi Tisseh
•
Ayoob Bazgir
Received: 14 August 2010 / Accepted: 12 July 2011 / Published online: 18 August 2011
Ó Springer-Verlag 2011
Abstract An efficient and simple synthesis of spiro[11H-
benzo[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-20,5,-
10(10H)-triones and spiro[acenaphthylene-1(2H),110-[11H]-
dunnione, dunniol, and dunnione) from Streptocapus dun-
nii have been isolated and characterized [7, 8]. On the other
hand, pyrazolo[3,4-b]quinolines belong to a class of highly
fluorescent compounds which emit mostly in the blue
spectral range and have been classified as promising
materials for optoelectronics [9]. Attempts have been made
to produce redshifts in their fluorescence spectra by
changing substituents [10].
benzo[g]pyrazolo[4,3-b]quinoline]-2,50,100-triones by
a
three-component condensation reaction of 2-hydroxy-1,4-
naphthoquinone, pyrazol-5-amines, and isatins or ace-
naphthylene-1,2-dione in the presence of p-TSA as an
inexpensive and available catalyst in refluxing ethanol
is reported.
Indole and indoline fragments are important moieties in
a large number of natural biologically active compounds
[11], and some indolines that are spiro-annulated with
heterocycles at the 3 position have shown high biological
activity [12–15]. The spirooxindole system is the core
structure of many pharmacological agents and natural
alkaloids [16–19]. Therefore, a number of methods have
been reported for the preparation of spirooxindoles
[20–23].
Keywords Isatin ꢀ Spirooxindole ꢀ Aminopyrazole ꢀ
Spiro[benzopyrazoloquinoline-indoline]
Introduction
Fluorescent heterocyclic compounds are of interest in
many disciplines; for example, they are used as emitters for
electroluminescence devices [1], molecular probes for
biochemical research [2], in traditional textile and polymer
fields [3], in fluorescent whitening agents [4], and in
photoconducting materials [5].
Considering the above reports, and as part of our pro-
gram aiming at the synthesis of heterocycles [24–33], we
are currently investigating the synthesis of new spiroox-
indoles containing pyrazolo[3,4-b]quinoline via a facile,
atom-economical, and one-pot condensation reaction.
Molecules with a naphthoquinone structure, due to their
biological properties, constitute one of the most interesting
classes of compounds in organic chemistry. They have also
industrial applications and can potentially be used as
intermediates in the synthesis of heterocycles [6]. A series
of related naphthoquinone pigments (streptocarpone, a-
Results and discussion
We found that a mixture of 2-hydroxy-1,4-naphthoquinone
(1), pyrazol-5-amines 2a–2d, and isatins 3a–3e in the
presence of a catalytic amount of p-TSA (15 mol%) in
refluxing ethanol for 4–5.5 h afforded spiro[11H-benzo[g]-
pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-20,5,10(10H)-
triones 4 in good yields (Scheme 1). Using this method,
some new spirooxindoles 4a–4j were selectively synthe-
sized by a three-component condensation reaction. The
results are summarized in Table 1.
M. Dabiri (&) ꢀ Z. N. Tisseh ꢀ A. Bazgir (&)
Department of Chemistry, Shahid Beheshti University,
G.C., P.O. Box 19396-4716, Tehran, Iran
e-mail: m-dabiri@sbu.ac.ir
A. Bazgir
e-mail: a_bazgir@sbu.sc.ir
123

140
M. Dabiri et al.
Scheme 1
O
H
O
O
N
Ph
O
Ph
p-TSA
(15 mol%)
OH
X
N
O
O
N
NH2
N
X
N
Ar
N
EtOH, reflux
R
Ar
O
N
R
1
2a-2d
3a-3e
4a-4j
elemental analysis. Electronic absorption and fluorescence
spectra of 5 9 10-5 M solutions of the selected products 4
and 6 in methanol were measured, and the results are
shown in Table 2. A fluorescence excitation (kex) wave-
length of 465 nm was used for compounds 4 and 6.
Figures 1, and 2 show the visible and emission spectra of
the selected products. From Fig. 2, it can be observed that
the products are fluorescent in solution. The kem values are
presented in Table 2.
Table 1 Synthesis of spiro[indoline-benzopyrazoloquinoline] deriv-
atives 4a–j
Derivative
Ar
X
R
Yield/%a
4a
4b
4c
4d
4e
4f
C6H5
H
H
94
87
83
90
80
81
80
73
81
85
4-MeO–C6H4
4-Br–C6H4
4-NO2–C6H4
C6H5
H
H
H
H
H
H
Br
Br
NO2
NO2
Me
H
Et
Et
H
4-MeO–C6H4
C6H5
In conclusion, we have described a facile three-com-
ponent method for the synthesis of spiro[11H-benzo[g]-
pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-20,5,10(10H)-
triones and spiro[acenaphthylene-1(2H),110-[11H]benzo[g]-
pyrazolo[4,3-b]quinoline]-2,50,100-triones in ethanol using
readily available starting materials. Prominent among the
advantages of this new method are operational simplicity,
good yields in short reaction times, and the easy work-up
procedures employed.
4g
4h
4i
4-NO2–C6H4
C6H5
H
H
4j
4-Br–C6H4
PhCH2
a
Isolated yields
To the best of our knowledge, this new procedure provides
the first example of a synthesis of spirooxindole-annulated
benzopyrazoloquinolines. The reactions in ethanol are
relatively safe, nontoxic, environmentally friendly, and
inexpensive. This method is most simple and convenient,
and would be applicable for the synthesis of different typesof
spiro[benzopyrazoloquinoline-indoline] derivatives. In
addition, the workup for these very clean reactions involves
only a filtration and a simple washing step with EtOH.
We have not established an exact mechanism for the
formation of product 4, but a reasonable possibility is
shown in Scheme 2.
Experimental
Melting points were measured on an Electrothermal 9100
apparatus. IR spectra were recorded on a Shimadzu IR-470
1
spectrometer. H NMR spectra were recorded on a Bruker
DRX-300 Avance spectrometer at 300.13 MHz. MS spectra
were recorded on a Shimadzu QP 1100EX mass spec-
trometer operating at an ionization potential of 70 eV.
Elemental analyses were performed using a Heraeus CHN-O-
Rapid analyzer, and results agreed favorably with calcu-
lated values. Absorption spectra were recorded on a
Shimadzu UV-2100 spectrophotometer. Fluorescence
spectra were recorded using a PerkinElmer LS45 spectro-
fluorophotometer. Chemicals were purchased from Fluka
or Merck and used as received.
As expected, when the isatin 3 was replaced by
acenaphthylene-1,2-dione (5), the spiro[acenaphthylene-
1(2H),110-[11H]benzo[g]pyrazolo[4,3-b]quinoline]-2,50,100-
triones 6 were obtained in good yields under the same
reaction conditions (Scheme 3).
Compounds 4 and 6 are stable solids whose structures
were established by IR and 1H NMR spectroscopy and
Scheme 2
Ph
N
N
O
O
O
Ph
N
H2N
NH
O
OH
O
OH
Ar
HO
HO
O
H
H2N
-H2O
N
O
N
H
4
Ar
O
-H2O
O
O
N
H
123

Synthesis of spiro[benzopyrazoloquinoline-indoline]triones
141
Scheme 3
O
H
N
Ph
O
O
O
Ph
p-TSA (15 mol%)
N
OH
O
N
N
NH2
EtOH, reflux
4h
N
Ar
Ar
O
O
1
2a-2c
5
Ar= C6H5
Ar= 4-MeO-C6H4
Ar= 4-Br-C6H4
93%
88%
85%
6a
6b
6c
Table 2 UV-vis and fluorescence emission data for compounds 4 and
6 in methanol
Entry
Product
k
abs/nm
log e
kem/nm
1
4a
4b
4c
4d
4e
4f
462
475
471
471
473
476
477
463
470
477
478
477
484
3.44
3.55
3.41
3.39
3.60
3.58
3.45
3.60
3.74
3.54
3.70
3.49
3.67
628
626
629
630
631
626
635
619
628
633
626
633
648
2
3
4
5
6
7
4g
4h
4i
8
9
Fig. 2 The emission spectra of the selected compounds 4 and 6
(5 9 10-5 M in methanol)
10
11
12
13
4j
6a
6b
6c
refluxing EtOH was stirred for 4 h. After the reaction had
completed, as confirmed by TLC (eluent: EtOAc/n-hexane
1:3), the reaction mixture was filtered and the precipitate
washed with water and then 5 cm3 EtOH to afford the pure
products. Due to the very low solubility of the products, we
are unable to report the 13C NMR data for these products.
1,4-Dihydro-1,3-diphenylspiro[11H-benzo[g]pyrazolo-
[4,3-b]quinoline-11,30-[3H]indole]-20,5,10(10H)-trione
(4a, C33H20N4O3)
ꢀ
Red powder; m.p.: 267–270 °C; IR (KBr): m = 3,426,
1
3,343, 1,755, 1,727, 1,678 cm-1; H NMR (DMSO-d6):
d = 6.61–8.57 (18H, m, arom), 10.46 (1H, s, NH), 11.47
(1H, s, NH) ppm; MS: m/z = 520 (M?).
1,4-Dihydro-1-(4-methoxyphenyl)-3-phenylspiro[11H-
benzo[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-
20,5,10(10H)-trione (4b, C34H22N4O4)
Fig. 1 The visible spectra of the selected compounds 4 and 6
(5 9 10-5 M in methanol)
Typical procedure for the preparation of compounds 4
and 6
Dark red powder; m.p.: 260–262 °C; IR (KBr): ꢀm = 3,343,
1
3,200, 1,745, 1,650, 1,615 cm-1; H NMR (DMSO-d6):
d = 3.86 (1H, s, OCH3), 6.67 (3H, d, J = 4.6 Hz, arom),
7.15–7.39 (8H, m, arom), 7.60 (2H, d, J = 8.1 Hz, arom),
7.79 (3H, bs, arom), 8.07 (1H, d, J = 6.5 Hz, arom), 9.90
(1H, s, NH), 10.09 (1H, s, NH) ppm; MS: m/z = 550 (M?).
A mixture of isatin or acenaphthylene-1,2-dione (1 mmol),
1H-pyrazol-5-amine (1 mmol), 2-hydroxy-1,4-naphtho-
quinone (1 mmol), and p-TSA (15 mol%) in 5 cm3
123

142
M. Dabiri et al.
1-(4-Bromophenyl)-1,4-dihydro-3-phenylspiro[11H-benzo-
[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-
20,5,10(10H)-trione (4c, C34H21BrN4O3)
1,4-Dihydro-50-methyl-1,3-diphenylspiro[11H-
benzo[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-
20,5,10(10H)-trione (4i, C34H22N4O3)
Orange powder; m.p.: 254–257 °C; IR (KBr): ꢀm = 3,150,
Red powder; m.p.: [300 °C; IR (KBr): ꢀm = 3,194, 3,056,
1,716, 1,678 cm-1; 1H NMR (DMSO-d6): d = 2.17 (3H, s,
CH3), 6.49–8.05 (17H, m, arom), 10.02 (1H, s, NH), 10.07
(1H, s, NH) ppm; MS: m/z = 534 (M?).
1
3,056, 1,711, 1,679, 1,644 cm-1; H NMR (DMSO-d6):
d = 6.44 (1H, d, J = 8.6 Hz, arom), 6.63 (2H, d,
J = 7.3 Hz, arom), 6.90–7.82 (13H, m, arom), 8.07 (1H,
d, J = 8.7 Hz, arom), 12.10 (1H, s, NH), 12.49 (1H, s, NH)
ppm; MS: m/z = 600 ([M ? 2]?), 598 (M?).
1-(4-Bromophenyl)-1,4-dihydro-3-phenyl-10-
(phenylmethyl)spiro[11H-benzo[g]pyrazolo[4,3-b]-
quinoline-11,30-[3H]indole]-20,5,10(10H)-trione
(4j, C40H25BrN4O3)
1,4-Dihydro-1-(4-nitrophenyl)-3-phenylspiro[11H-
benzo[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-
20,5,10(10H)-trione (4d, C33H19N5O5)
ꢀ
Red powder; m.p.: [300 °C; IR (KBr): m = 3,211, 1,710,
Red powder; m.p.: [300 °C; IR (KBr): m = 3,210, 3,061,
1,681, 1,623 cm-1; 1H NMR (DMSO-d6): d = 3.91 (1H, d,
J = 16 Hz, CH2), 4.79 (1H, d, J = 16 Hz, CH2), 6.42 (1H,
d, J = 8.9 Hz, arom), 6.62 (2H, d, J = 6.5 Hz, arom),
6.91–7.83 (18H, m, arom), 8.09 (1H, d, J = 8.9 Hz, arom),
10.11 (1H, s, NH) ppm; MS: m/z = 690 ([M ? 2]?), 688
(M?).
ꢀ
1,715, 1,676, 1,644 cm-1; 1H NMR (DMSO-d6): d = 8.72
(1H, d, J = 9.0 Hz, arom), 8.94 (2H, d, J = 8.1 Hz, arom),
9.36–10.03 (13H, m, arom), 10.25 (1H, d, J = 8.9 Hz,
arom), 10.05 (1H, s, NH), 10.18 (1H, s, NH) ppm; MS:
m/z = 565 (M?).
50-Bromo-10-ethyl-1,4-dihydro-1,3-diphenylspiro[11H-
benzo[g]pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-
20,5,10(10H)-trione (4e, C35H23BrN4O3)
10,40-Dihydro-10,30-diphenylspiro[acenaphthylene-
1(2H),110-[11H]benzo[g]pyrazolo[4,3-b]quinoline]-
2,50,100-trione (6a, C37H21N3O3)
ꢀ
ꢀ
Red powder; m.p.: 268–271 °C; IR (KBr): m = 3,255, 1,722,
Red powder; m.p.: 252–255 °C; IR (KBr): m = 3,205,
1,705, 1,677 cm-1; H NMR (DMSO-d6): d = 0.83 (3H, bs,
CH3), 3.15 (2H, bs, CH2), 6.63–8.05 (17H, m, arom), 9.98
(1H, s, NH) ppm; MS: m/z = 628 ([M ? 2]?), 626 (M?).
1,718, 1,670, 1,607 cm-1; 1H NMR (DMSO-d6): d = 6.17
(2H, d, J = 6.6 Hz, arom), 6.60 (2H, t, J = 6.3 Hz, arom),
6.85 (1H, t, J = 6.1 Hz, arom), 7.49–8.12 (15H, m, arom),
10.05 (1H, s, NH) ppm; MS: m/z = 555 (M?).
50-Bromo-10-ethyl-1,4-dihydro-1-(4-methoxyphenyl)-3-phe-
nylspiro[11H-benzo[g]pyrazolo[4,3-b]quinoline-11,30-
[3H]indole]-20,5,10(10H)-trione (4f, C36H25BrN4O4)
Dark red powder; m.p.: 253–256 °C; IR (KBr): ꢀm = 3,360,
1,749, 1,705, 1,639 cm-1; 1H NMR (DMSO-d6): d = 1.05
(3H, bs, CH3), 3.42 (2H, bs, CH2), 3.85 (3H, s, OCH3),
6.68–8.06 (17H, m, arom), 10.01 (1H, s, NH) ppm; MS:
m/z = 658 ([M ? 2]?), 656 (M?).
10,40-Dihydro-10-(4-methoxyphenyl)-30-phenylspiro-
[acenaphthylene-1(2H),110-[11H]benzo[g]pyrazolo-
[4,3-b]quinoline]-2,50,100-trione (6b, C38H23N3O4)
ꢀ
Red powder; m.p.: 263–266 °C; IR (KBr): m = 3,183,
1,705, 1,678, 1,611 cm-1; 1H NMR (DMSO-d6): d = 3.86
(3H, s, CH3), 6.15 (2H, d, J = 8.7 Hz, arom), 6.59 (2H, t,
J = 8.9 Hz, arom), 6.85 (1H, t, J = 8.4 Hz, arom), 7.15
(2H, d, J = 8.9 Hz, arom), 7.48–8.13 (12H, m, arom), 9.92
(1H, s, NH) ppm; MS: m/z = 585 (M?).
1,4-Dihydro-50-nitro-1,3-diphenylspiro[11H-benzo[g]-
pyrazolo[4,3-b]quinoline-11,30-[3H]indole]-20,5,10(10H)-
trione (4g, C33H19N5O5)
10-(4-Bromophenyl)-10,40-dihydro-30-phenylspiro[acenaph-
thylene-1(2H),110-[11H]benzo[g]pyrazolo[4,3-b]quino-
line]-2,50,100-trione (6c, C37H20BrN3O3)
ꢀ
Dark red powder; m.p.: 270–273 °C; IR (KBr): m = 3,426,
3,327, 1,705, 1,672, 1,650 cm-1; H NMR (DMSO-d6):
1
ꢀ
d = 6.70 (3H, d, J = 7.4 Hz, arom), 7.15–8.06 (13H, m,
arom), 8.51 (1H, d, J = 6.4 Hz, arom), 10.84 (1H, s, NH),
11.16 (1H, s, NH) ppm; MS: m/z = 565 (M?).
Red powder; m.p.: 266–269 °C; IR (KBr): m = 3,200,
1,711, 1,678, 1,617 cm-1 1H NMR (DMSO-d6):
;
d = 6.14–8.08 (19H, m, arom), 10.26 (1H, s, NH) ppm;
MS: m/z = 635 ([M ? 2]?), 633 (M?).
1,4-Dihydro-50-nitro-1-(4-nitrophenyl)-3-phenylspiro-
[11H-benzo[g]pyrazolo[4,3-b]quinoline-11,30-
[3H]indole]-20,5,10(10H)-trione (4h, C33H18N6O7)
Acknowledgments We gratefully acknowledge financial support
from the Research Council of Shahid Beheshti University.
ꢀ
Dark red powder; m.p.: [300 °C; IR (KBr): m = 3,418,
1
3,329, 1,711, 1,670, 1,653 cm-1; H NMR (DMSO-d6):
d = 6.51 (1H, d, J = 8.3 Hz, arom), 6.75 (2H, d,
J = 7.9 Hz, arom), 7.12–7.82 (12H, m, arom), 8.06 (1H,
d, J = 6.4 Hz, arom), 10.28 (1H, s, NH), 10.59 (1H, s, NH)
ppm; MS: m/z = 610 (M?).
References
1. Hunger K (2003) Industrial dyes. Wiley-VCH, Weinheim, p 569
2. Dmitry A, Pavel A (2003) Chem Commun 12:1394
123

Synthesis of spiro[benzopyrazoloquinoline-indoline]triones
143
3. Gold H (1971) In: Venkataraman H (ed) The chemistry of syn-
thetic dyes. Pergamon, New York, p 535
19. Khafagy MM, Abd El-Wahab AHF, Eid FA, El-Agrody AM
(2002) Farmaco 57:715
4. Belgodere E, Bossio R, Chimichi S, Passini V, Pepino R (1985)
Dyes Pigm 4:59
5. Kalle AG (1962) British Patent 1962;895(001)
6. Thomson RH (1997) Naturally occurring quinines, 4th edn.
Chapman & Hall, London
20. Nandakumar A, Thirumurugan P, Perumal PT, Vembu P, Pon-
nuswamy MN, Ramesh P (2010) Bioorg Med Chem Lett 20:4252
21. Chen H, Shi D (2010) J Comb Chem 12:571
22. Chen T, Xu XP, Ji SJ (2010) J Comb Chem 12:659
23. Li Y, Chen H, Shi C, Shi D, Ji S (2010) J Comb Chem 12:231
24. Bazgir A, Seyyedhamzeh M, Yasaei Z, Mirzaei P (2007) Tetra-
hedron Lett 48:8790
7. Perez AL, Lamoureux G, Sanchez-Kopper A (2007) Tetrahedron
Lett 48:3735
8. Inoue K, Ueda S, Nayeshiro H, Inouye H (1982) Chem Pharm
Bull 30:2265
25. Sayyafi M, Seyyedhamzeh M, Khavasi HR, Bazgir A (2008)
Tetrahedron 64:2375
9. Tao YT, Balasubramaniam E, Danel A, Wisla A, Tomasik P
(2001) J Mater Chem 11:768
10. Gondek E, Kityk IV, Danel A, Wisla A, Pokladko M, Sanetra J,
Sahraoui B (2006) Mater Lett 60:3301
11. Sundberg RJ (1996) The chemistry of indoles. Academic, New
York
12. Joshi KC, Chand P (1982) Pharmazie 37:1
13. Da Silva JFM, Garden SJ, Pinto AC (2001) J Braz Chem Soc
12:273
26. Dabiri M, Delbari AS, Bazgir A (2007) Synlett 821
27. Dabiri M, Arvin-Nezhad H, Khavasi HR, Bazgir A (2007) Tet-
rahedron 63:1770
28. Ghahremanzadeh R, Imani Shakibaei G, Bazgir A (2008) Synlett
1129
29. Bazgir A, Noroozi Tisseh Z, Mirzaei P (2008) Tetrahedron Lett
49:5165
30. Ghahremanzadeh R, Sayyafi M, Ahadi S, Bazgir A (2009) J
Comb Chem 11:393
14. Abdel-Rahman AH, Keshk EM, Hanna MA, El-Bady SM (2004)
Bioorg Med Chem 12:2483
31. Ghahremanzadeh R, Ahadi S, Imani Shakibaei G, Bazgir A
(2010) Tetrahedron Lett 51:499
15. Zhu SL, Ji SJ, Yong Z (2007) Tetrahedron 63:9365
16. Kang TH, Matsumoto K, Tohda M, Murakami Y, Takayama H,
Kitajima M, Aimi N, Watanabe H (2002) Eur J Pharmacol 444:39
17. Ma J, Hecht SM (2004) Chem Commun 1190
18. Usui T, Kondoh M, Cui CB, Mayumi T, Osada H (1998) Bio-
chem J 333:543
32. Ghahremanzadeh R, Imani Shakibaei GH, Ahadi S, Bazgir A
(2010) J Comb Chem 12:191
33. Jadidi K, Ghahremanzadeh R, Bazgir A (2009) J Comb Chem
11:341
123