InCl3-mediated eco-friendly three-component domino reaction for synthesis of highly functionalized triazolylspiroxindolinopyrans and triazolylpyrans under solvent-free conditions

Article abstract of DOI:10.1039/c4ra01524j

A one pot domino protocol has been developed for the efficient synthesis of novel triazolylspiroxindolinopyrans and triazolylpyran derivatives. The synthesis was achieved by reacting phenacyltriazole, isatin/aromatic aldehyde and active methylene compounds in the presence of InCl₃ under solvent-free conditions at 100 °C. This novel strategy affording biologically relevant heterocyclic compounds presumably involves Knoevenagel condensation/Michael addition/6-exo-dig-cyclisation sequences. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra01524j

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InCl3-mediated eco-friendly three-component
domino reaction for synthesis of highly
Cite this: RSC Adv., 2014, 4, 19422
functionalized triazolylspiroxindolinopyrans and
triazolylpyrans under solvent-free conditions†
*
Jayabal Kamalraja, Potharaj Murugasan and Paramasivan Thirumalai Perumal
A
one pot domino protocol has been developed for the efficient synthesis of novel
triazolylspiroxindolinopyrans and triazolylpyran derivatives. The synthesis was achieved by reacting
phenacyltriazole, isatin/aromatic aldehyde and active methylene compounds in the presence of InCl3
under solvent-free conditions at 100 ꢀC. This novel strategy affording biologically relevant heterocyclic
compounds presumably involves Knoevenagel condensation/Michael addition/6-exo-dig-cyclisation
sequences.
Received 21st February 2014
Accepted 4th April 2014
DOI: 10.1039/c4ra01524j
www.rsc.org/advances
example, spirotryprostatin A5 is one of the natural alkaloids
isolated from Aspergillus fumigatus, and has been identied as a
Introduction
novel inhibitor of microtubule assembly, and pteropodine and
isopteropodine have been shown to modulate the function of
muscarinic serotonin receptors.6 Similarly, many of the spiro-
oxindole frameworks deliver important pharmacological
activity such as vasodilatory, hypoglycaemic, anti-inammatory,
analgesic and antipyretic activities.7 Owing to the unique
pharmacological properties of the spiro-oxindole framework,
the development of synthetic methods enabling facile access to
this heterocyclic is still desirable.
Multi-functionalized 4H-pyrans are an important class of
compounds present in several natural or synthetic products
with important biological or pharmacological activities such as
anticoagulant, anticancer, antioxidant, spasmolytic, diuretic,
and anti-anaphylactic activities.8 In particular, large numbers of
Synthetic organic chemistry lies at the heart of modern drug
discovery and developments in that eld. It consists of making
or breaking carbon–carbon (C–C) and carbon–heteroatom (C–X)
bonds for construction of biologically signicant heterocyclic
compounds. This synthetic methodology resulting in simple to
complex structural diversity with the minimum number of steps
and reasonable yields in both academic and industrial settings
is highly desirable. Multicomponent reactions (MCR)1 have
emerged as a powerful tool for delivering highly functionalized
small and complex molecules mimicking important natural
products that are promising candidates as probes in chemical
biology to investigate biological phenomena and for drug
development. Owing to ecological concerns, organic chemists
pay much attention to synthetic pathways for greener
approaches to reduce the drastic prerequisites for reaction. Due
to the harmful effects of organic solvents on the environment
and humans, solvent-free reactions have become a powerful
tool in organic synthesis for delivering a huge number of bio-
logically important heterocyclics in greener approaches.
Furthermore, solvent-free reactions offer several advantages
such as faster reaction rate, reduced reaction time, lower energy
consumption, easy separation, and products with high yields
and purity.2
The spiro-oxindole ring system has acquired a special place
in the heterocyclic eld since it is a frequently encountered
structural motif in many natural alkaloids3,4 (Fig. 1). For
Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai
600020, Tamilnadu, India. E-mail: ptperumal@gmail.com; Fax: +91 44 24911589
† Electronic supplementary information (ESI) available: 1H and 13C NMR spectra
of all compounds. CCDC 953661 for 5x. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c4ra01524j
Fig. 1 Typical natural products containing spiro-oxindole scaffolds.
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2-amino-4H-pyran derivatives are used as photoactive materials, more acidic active methylene hydrogen undergoes keto–enol
cosmetics, and pigments.9
tautomerism to give alcohol, a precursor of the oxygen hetero-
Usually, oxindole derivatives containing spirocarbon and cyclics. Based on these key features, herein we demonstrate the
heterocyclics at the C3 position enhance their biological use of the special reactivity of phenacyltriazole for convenient
activity.10 Isatin and its derivatives play an important role in the combinatorial synthesis of triazolylspiroxindolinopyrans. In
synthesis of oxindoles and are widely used as precursors for recent times, the utility of indium(III) Lewis acids16 in organic
many natural products.11 This encouraged us to focus on Target synthesis has received much attention because of their
Oriented Synthesis (TOS) to design novel heterocyclic biocompatibility, such as lower toxicity, stability in air and
compounds with new synthetic methodology for the efficient water, and recyclability. To the best of our knowledge, there
synthesis of triazolylspiroxindolinopyrans.
have been no reports on the synthesis of triazole derivatives,
Click chemistry12 is a modular approach that uses only the including spiropyranyl moieties using phenacyltriazoles as a
most practical and reliable chemical transformations. In new synthon. As part of our effort to develop heterocyclic
particular, Huisgen [3 + 2] cycloaddition13 has emerged as a compounds with biological potential by new synthetic
‘near perfect’ (very fast, selective, high-yield, and wide scope) methods,17,18 and to apply InCl3 in organic synthesis,19 we report
carbon–nitrogen bond forming reaction in the synthesis of N- for the rst time the facile and efficient synthesis of tri-
substituted 1,2,3-triazoles. This process, which occurs between azolylspiroxindolinopyrans by
a one-pot three-component
organic azides and alkynes, is signicantly accelerated by Cu(I) coupling of 1-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl) etha-
catalysis14 and it offers easy access to the 1,4-disubstituted none, substituted isatin and active methylenes under solvent-
ꢀ
isomer. The triazole products are more than just passive linkers; free conditions at 100 C in the presence of InCl3 (Scheme 1).
they readily associate with biological targets, through hydrogen
The reactions were accomplished within 1–2 h and the pure
bonding and dipole interactions. Their applications are solid products were sequestered in good yields by simple
increasingly found in all aspects of drug discovery, ranging from addition of ethanol to the reaction mixture. The synthetic route
lead nding through combinatorial chemistry and target- is more facile, convenient and permits easy placement of pyran
template in situ chemistry, to proteomics and DNA research, with triazole heterocyclics in the spiro-oxindole core to deliver a
using bioconjugation reactions.15 Based on these pharmaco- new hybrid of the heterocyclic ring system.
logical applications, we incorporated a spiro-oxindole core in a
The precursor phenacyltriazoles were synthesized in good
triazole motif to obtain a hybrid molecule of triazolylspiroox- yield (75–85%) within 2 h by the reaction of substituted phe-
indolopyran with greater biological impact and enhanced bio- nacyl bromide and sodium azide with phenylacetylene in the
logical activity.
presence of CuI in acetone (Table 1) and used for synthesis of
novel triazolylspiroxindolinopyrans.
For the initial investigation, phenacyltriazole, isatin and
malononitrile were selected as a trial substrate to optimize the
reaction conditions. Initially, the above three-component reac-
tion was carried out at room temperature in EtOH followed by
reux without any catalyst to establish the real effectiveness of
the catalyst. There was no product formation even aer 24 h.
Next, we tried to optimize the reaction conditions with different
catalysts, different amounts of catalyst and different solvents.
When the reaction was carried out in Et3N and ethanol
combination, only 50% product conversion was observed. In
order to enhance the yield, looking for other effective method-
ology was highly desirable. The solvent-free condition is a
powerful technique to deliver large amounts of heterocyclics in
an eco-compatible manner. We used this technique and
obtained good yields in the minimum reaction period.
Results and discussion
This novel strategy to introduce a synthon which has a biolog-
ically important heterocyclic core triazole with an active methyl
group has great potential for the development of triazolylspir-
oxindolinopyrans in an effective manner. 1-Phenyl-2-(4-phenyl-
1H-1,2,3-triazol-1-yl)ethanone is one such versatile interme-
diate, with an active methylene ketone motif (Fig. 2). Due to the
electron withdrawing nature of carbonyl and triazole groups,
the central –CH2 group acts as an active methylene group and
hence is a good Michael donor. In the presence of catalyst, the
Next we optimized the catalytic loading and temperature of
reaction. To our delight, the catalytic amount of 20 mol% and
Fig. 2 The special reactive profile of phenacyltriazole.
Scheme 1 Synthesis of triazolylspiroxindolinopyrans 5.
RSC Adv., 2014, 4, 19422–19432 | 19423
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Table 1 Synthesis of phenacyltriazoles 2
acenaphthoquinone were well tolerated and the products were
obtained in high yields (Table 3).
Aer successfully completing the synthesis of the spiro-motif
from isatin/acenaphthoquinone, malononitriles and phenacyl-
triazoles, we next applied the same methodology with aromatic
aldehydes to determine generality of this protocol. We obtained
highly substituted triazolylpyrans in good yields (Scheme 2 and
Table 4).
Entry
R1
R2
Product
Yielda
Table 3 Synthesis of triazolylspiroxindolinopyrans 5a
1
2
3
4
H
Cl
Br
C4H4
H
H
H
2a
2b
2c
2d
79
83
85
75
a
Isolated yield.
100 ꢀC were found to be the optimum reaction conditions.
Increasing or decreasing the amount of catalyst as well as
temperature resulted in a signicant reduction in yield, even
with increased reaction times (Table 2).
With these straightforward reaction conditions, to delineate
this approach, the scope and generality of this protocol was next
examined by employing various phenacyltriazoles, different
isatins and active methylenes. Notably, a variety of substituted
isatins (including aromatic and N-substitution) and
Table 2 Optimization of reaction conditionsa for the synthesis of tri-
azolylspiroxindolinopyran 5a
Entry Reaction condition
Time (h) Yieldb (%)
c
1
2
3
4
5
6
7
8
No catalyst, EtOH, rt
No catalyst, EtOH, reux
24
8
24
10
6
7
8
6
8
6
6
4
2
6
8
12
2
—
—
—
c
c
Piperidine (0.1 eq.), EtOH, rt
Piperidine (0.1 eq.), EtOH, reux
TEA (1.0 eq.), EtOH, reux
DABCO (1.0 eq.), EtOH, reux
L-Proline (1.0 eq.), EtOH, reux
p-TSA (1.0 eq.), EtOH, reux
CAN (1.0 eq.), EtOH, reux
InCl3 (0.10 eq.), EtOH, reux
InCl3 (0.20 eq.), EtOH, reux
43
45
47
28
42
c
9
—
55
58
74
92
90
68
48
31
10
11
12
13
14
15
16
17
InCl3 (0.1 eq.), solvent-free, 80 ꢀ
InCl3 (0.20 eq.), solvent-free, 100 ꢀ
InCl3 (0.20 eq.), solvent-free, 120 ꢀ
C
C
C
Cu(TfO)3 (0.20 eq.), solvent-free, 100 ꢀ
FeCl3 (0.20 eq.), solvent-free, 100 ꢀC
C
I2 (0.20 eq.), solvent-free, 100 ꢀ
C
a
Reactions were carried out using 2 (1.0 mmol), 3 (1.0 mmol), and 4 (1.0
mmol). b Isolated yield. c No reaction.
Product 5 (time in h, yield %).
a
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Table 4 Synthesis of triazolylpyrans 7a
Scheme 3 Plausible mechanisms for the formation of triazolylspir-
oxindolinopyrans 5.
cyclisation to provide 9. Finally, 9 undergoes proton migration
to yield triazolylspiroxindolinopyran 5 in good yield.
Our efforts to isolate intermediates, other than 6, by inter-
cepting the reaction at various times before completion of the
reaction failed, as only mixtures of intermediate 6, reactant 2
and the nal product 5 were found in varying amounts in the
reaction mixture. This shows that, under these reaction condi-
tions, once intermediate 6 is formed, the subsequent Michael
addition between 2 and 6 followed by 6-exo-dig-cyclisation to
give the nal product 5 occurs relatively rapidly.
The main advantages of this domino protocol are the simple
workup, and that the product is obtained in high purity simply
by trituration with ethanol, which makes this methodology
facile, practical, and rapid to perform. The purity of the product
was sufficient for spectroscopic analysis without any further
purication. The structures of all of the newly synthesized
compounds 5 and 7 were well characterized from their satis-
factory spectra (IR, 1H, 13C NMR, and mass) data. The mass
spectra of the synthesised compounds displayed molecular ion
peaks at the appropriate m/z values. Further, the structure was
explicitly established by single crystal X-ray diffraction analysis
of compound 5x (Fig. 3).20
a
Product 7 (time in h, yield %).
Based on the above results, a plausible mechanism is
proposed for the formation of triazolylspiroxindolinopyrans 5
(Scheme 3). Initially, isatin 3 reacts with malononitrile 4 to give
an isatylidene malononitrile adduct 6 which acts as a Michael
acceptor, and phenacyltriazole 2 may exist as a keto–enol
tautomer with the inuence of InCl3 which acts as a Michael
donor 2a. The intermediate 2a undergoes Michael type addition
to 6 to provide open chain intermediate 7. This intermediate
may exist as a keto–enol tautomer 8. This 8 undergoes 6-exo-dig-
Scheme 2 Synthesis of triazolylpyrans.
Fig. 3 ORTEP diagram of compound 5x.
RSC Adv., 2014, 4, 19422–19432 | 19425
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20-Amino-1-methyl-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5b)
Conclusion
The present work describes for the rst time a domino three-
component protocol to assemble a series of hitherto unreported
triazolylspiroxindolinopyrans and triazolylpyrans from the
sequential reaction of phenacyltriazoles, isatin/aromatic alde-
hyde and active methylene compound in the presence of InCl3
as green catalyst under solvent-free conditions. The notable
features of this methodology are that the three biologically
important core moieties are brought into a single molecule
utilizing green catalyst solvent-free reaction conditions with the
formation of only water as by-product and avoiding tedious
separation techniques such as column chromatography and
recrystallization from ethanol. Hence, a green transformation.
1
White solid; mp 172–174 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.12 (s, 1H), 7.62 (s, 2H), 7.56 (d, J ¼ 7.3 Hz, 2H), 7.45 (d, J ¼ 7.2
Hz, 1H), 7.41–7.12 (m, 9H), 7.03 (t, J ¼ 7.3 Hz, 1H), 6.90 (d, J ¼
7.6 Hz, 1H), 3.10 (s, 3H). 13C NMR (101 MHz, DMSO-d6) d 175.43,
161.02, 149.24, 146.31, 143.78, 131.18, 130.23, 130.02, 129.70,
129.32, 129.10, 129.04, 128.61, 127.98, 125.49, 125.40, 124.28,
123.33, 117.78, 112.57, 109.22, 55.87, 52.71, 27.08. IR (KBr,
cmꢁ1): 3368, 3191, 2199, 1713, 1679, 1645, 1645, 1606, 1469,
1415, 1366, 1154, 1025, 875, 693; ESI-mass m/z: 473 (M+ + 1).
HRMS (ESI) calc. for C28H21N6O2 [M+ + 1] 473.17260, found:
473.17294.
1-Allyl-20-amino-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-triazol-
1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5c)
Experimental
General information
1
White solid; mp 168–170 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.12 (s, 1H), 7.62 (s, 2H), 7.56 (d, J ¼ 7.4 Hz, 2H), 7.49 (d, J ¼ 7.4
Hz, 1H), 7.40–7.24 (m, 7H), 7.20 (t, J ¼ 7.0 Hz, 3H), 7.04 (t, J ¼ 7.5
Hz, 1H), 6.79 (d, J ¼ 7.8 Hz, 1H), 5.80–5.61 (m, 1H), 5.06–5.0 (m,
2H), 4.27 (s, 2H). 13C NMR (101 MHz, DMSO-d6) d 175.20,
160.92, 149.46, 146.41, 142.82, 131.56, 131.18, 130.12, 130.06,
129.70, 129.34, 129.30, 129.03, 128.60, 127.98, 125.62, 125.53,
124.39, 123.37, 117.80, 116.97, 112.43, 109.87, 56.09, 52.85. IR
(KBr, cmꢁ1): 3452, 3184, 2193, 1711, 1644, 1605, 1486, 1360,
1284, 1026, 760, 630, 494; ESI-mass m/z: 499 (M+ + 1). HRMS
(ESI) calc. for C30H23N6O2 [M+ + 1] 499.18825, found: 499.18945.
Commercially available starting materials were used as received
without further purication. Infrared (IR) spectra were recorded
in KBr, and wavenumbers (n) are reported in cmꢁ1. 1H and 13
C
NMR spectra were recorded on a Bruker (400 MHz). Chemical
shis (d) are given in parts per million (ppm) with reference to
TMS. DMSO-d6 and CDCl3 were used as solvents. J values are
given in Hz. Standard Bruker soware was used throughout.
Mass spectra were recorded using electrospray ionization (ESI)
mass spectrometry; [M],+ [M+ + 1], [M+ + 2] mass peaks were
observed. The melting points are uncorrected.
20-Amino-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-triazol-1-yl)-1-
(prop-2-ynyl)spiro[indoline-3,40-pyran]-30-carbonitrile (5d)
General procedure for synthesis of
triazolylspiroxindolinopyrans 5
1
White solid; mp 166–168 ꢀC. H NMR (400 MHz, DMSO-d6) d
A dried, 10 mL round-bottomed ask was charged with phe-
nacyltriazole (1.0 mmol), isatin (1.0 mmol), and active methy-
lene compound (1.0 mmol), and 20 mol% of InCl3 was added to
the reaction mixture and heated in an oil bath at 100 ꢀC for the
stipulated period. Aer completion of the reaction (monitored
by TLC), ethanol (2 mL) was added to the reaction mixture. The
products appeared as solids, by trituration with ethanol, and
were ltered and washed with another 2 mL of EtOH to remove
other impurities. Finally, the products 5 were dried and were
pure enough for the spectral investigations.
8.09 (s, 1H), 7.65 (s, 2H), 7.56 (d, J ¼ 7.3 Hz, 2H), 7.49 (d, J ¼ 7.3
Hz, 1H), 7.42–7.30 (m, 5H), 7.26 (t, J ¼ 7.9 Hz, 2H), 7.19 (d, J ¼
7.4 Hz, 2H), 7.08 (t, J ¼ 7.5 Hz, 1H), 6.98 (d, J ¼ 7.8 Hz, 1H), 4.52
(dd, J ¼ 41.9, 17.8 Hz, 2H), 3.11 (s, 1H). 13C NMR (101 MHz,
DMSO-d6) d 174.83, 161.04, 149.52, 146.43, 141.93, 131.21,
130.20, 130.07, 129.70, 129.30, 129.08, 129.04, 128.60, 128.00,
125.68, 125.57, 124.13, 123.73, 117.55, 112.23, 109.94, 77.78,
74.90, 55.76, 52.70, 29.82. IR (KBr, cmꢁ1): 3454, 3307, 3191,
2196, 1710, 1640, 1609, 1485, 1467, 1361, 1237, 1090, 958, 875,
695, 536; ESI-mass m/z: 497 (M+ + 1). HRMS (ESI) calc. for
C
30H21N6O2 [M+ + 1] 497.17260, found: 497.17274, [M+ + Na]
519.15511.
20-Amino-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-triazol-1-yl)
spiro[indoline-3,40-pyran]-30-carbonitrile (5a)
20-Amino-5-chloro-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
White solid; mp 180–182 ꢀC. 1H NMR (400 MHz, DMSO) d 10.55
(s, 1H), 8.13 (s, 1H), 7.61–7.52 (m, 3H), 7.25–7.41 (m, 8H), 7.18
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5e)
1
(d, J ¼ 7.1 Hz, 2H), 7.12 (t, J ¼ 7.5 Hz, 1H), 6.96 (t, J ¼ 7.5 Hz, White solid; mp 176–178 ꢀC. H NMR (400 MHz, DMSO-d6) d
1H), 6.67 (d, J ¼ 7.7 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) d 10.73 (s, 1H), 8.22 (s, 1H), 7.65 (s, 2H), 7.60 (d, J ¼ 8.3 Hz, 3H),
176.94, 160.82, 149.21, 146.28, 142.32, 131.11, 130.14, 130.09, 7.40–7.27 (m, 6H), 7.24–7.17 (m, 3H), 6.71 (d, J ¼ 8.3 Hz, 1H).
130.06, 129.77, 129.33, 129.01, 128.60, 127.95, 125.77, 125.48, 13C NMR (101 MHz, DMSO-d6) d 176.77, 160.83, 149.55, 146.41,
124.41, 122.66, 117.89, 112.74, 110.22, 56.35, 53.20. IR (KBr, 141.18, 132.25, 131.21, 130.07, 130.00, 129.63, 129.39, 129.01,
cmꢁ1): 3352, 3192, 2206, 1712, 1683, 1618, 1602, 1473, 1300, 128.71, 128.05, 126.72, 126.02, 125.52, 124.47, 117.84, 111.93,
1226, 1087, 933, 696; ESI-mass m/z: 459 (M+ + 1). HRMS (ESI) 111.71, 55.74, 53.52. IR (KBr, cmꢁ1): 3449, 3350, 2203, 1735,
calc. for C27H19N6O2 [M+ + 1] 459.15695, found: 459.15738.
1694, 1652, 1588, 1478, 1293, 1164, 1029, 966, 818, 692, 558,
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462; ESI-mass m/z: 493 (M+ + 1). HRMS (ESI) calc. for 1725, 1693, 1494, 1455, 1350, 1196, 958, 856, 699543, 449; ESI-
27H17ClN6NaO2 [M+ + Na] 515.09992, found: 515.10109. mass m/z: 571 (M+ + 1), 573 (M+ + 2). HRMS (ESI) calc. for
27H17BrClN6O2 [M+ + 1] 571.02849, found: 571.01050.
C
C
20-Amino-5-bromo-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5f)
1-Allyl-20-amino-60-(4-chlorophenyl)-2-oxo-50-(4-phenyl-1H-
1
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5j)
White solid; mp 184–186 ꢀC. H NMR (400 MHz, DMSO-d6) d
1
10.71 (s, 1H), 8.22 (s, 1H), 7.69 (s, 1H), 7.63–7.59 (m, 4H), 7.38– White solid; mp 194–196 ꢀC. H NMR (400 MHz, DMSO-d6) d
7.27 (m, 7H), 7.21 (d, J ¼ 7.2 Hz, 2H), 6.65 (d, J ¼ 8.2 Hz, 1H). 13
C
8.15 (s, 1H), 7.65 (s, 2H), 7.58 (d, J ¼ 7.2 Hz, 2H), 7.49 (d, J ¼ 7.4
NMR (101 MHz, DMSO-d6) d 176.60, 160.83, 149.55, 146.40, Hz, 1H), 7.44 (d, J ¼ 8.7 Hz, 2H), 7.35 (t, J ¼ 7.4 Hz, 2H), 7.29 (d, J
141.60, 132.89, 132.63, 131.18, 130.05, 129.66, 129.37, 128.99, ¼ 7.3 Hz, 1H), 7.22–7.17 (m, 3H), 7.04 (t, J ¼ 7.5 Hz, 1H), 6.80 (d,
128.74, 128.69, 128.06, 125.54, 124.50, 117.83, 114.35, 112.19, J ¼ 7.8 Hz, 1H), 5.78–5.64 (m, 1H), 5.08–4.97 (m, 2H), 4.27 (d, J ¼
111.96, 55.79, 53.49. IR (KBr, cmꢁ1): 3399, 3352, 3120, 2197, 2.4 Hz, 2H). 13C NMR (101 MHz, DMSO-d6) d 174.52, 160.28,
1737, 1685, 1635, 1437, 1238, 1162, 1118, 969, 860, 771, 687, 147.86, 146.03, 142.25, 135.39, 130.97, 129.63, 129.42, 129.23,
505, 462; ESI-mass m/z: 537 (M+ + 1), 538 (M+ + 2). HRMS (ESI) 128.76, 128.68, 128.65, 128.11, 127.97, 125.08, 125.01, 123.70,
calc. for
559.04907.
C
27H17BrN6NaO2 [M+
+
Na] 559.04941, found: 122.84, 117.16, 116.41, 112.27, 109.34, 55.53, 52.28, 41.81. IR
(KBr, cmꢁ1): 3474, 3315, 3170, 2200, 1954, 1707, 1641, 1606,
1358, 1245, 989, 876, 711, 641, 521, 489; ESI-mass m/z: 533 (M+ +
1). HRMS (ESI) calc. for C30H21ClN6NaO2 [M+ + 1] 555.13122,
found: 555.13270.
20-Amino-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-triazol-1-yl)-
2H-spiro[acenaphthylene-1,40-pyran]-30-carbonitrile (5g)
1
White solid; mp 186–188 ꢀC. H NMR (400 MHz, DMSO-d6) d
Ethyl 20-amino-5-bromo-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
8.24 (d, J ¼ 8.1 Hz, 1H), 8.14 (s, 1H), 8.04 (d, J ¼ 7.0 Hz, 1H), 7.92
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carboxylate (5k)
(d, J ¼ 8.3 Hz, 1H), 7.86–7.75 (m, 2H), 7.74–7.63 (m, 3H), 7.45–
7.31 (m, 5H), 7.27 (t, J ¼ 7.4 Hz, 2H), 7.22 (t, J ¼ 6.8 Hz, 3H). 13
C
White solid; mp 220–222 ꢀC. H NMR (400 MHz, DMSO-d6) d
1
NMR (101 MHz, DMSO-d6) d 202.54, 160.82, 148.98, 145.93, 10.31 (s, 1H), 8.07 (s, 2H), 8.04 (s, 1H), 7.63 (d, J ¼ 7.2 Hz, 2H),
141.89, 138.10, 132.93, 131.20, 130.82, 130.24, 129.79, 129.70, 7.53 (d, J ¼ 1.9 Hz, 1H), 7.40–7.23 (m, 7H), 7.22–7.16 (m, 2H),
129.37, 129.33, 129.26, 129.09, 128.59, 127.99, 126.12, 125.34, 6.50 (d, J ¼ 8.2 Hz, 1H), 3.85–3.70 (m, 2H), 0.75 (t, J ¼ 7.1 Hz,
124.73, 123.29, 122.73, 118.00, 113.38, 57.23, 57.05. IR (KBr, 3H). 13C NMR (101 MHz, DMSO-d6) d 177.49, 166.82, 160.03,
cmꢁ1): 3377, 3316, 2201, 1720, 1681, 1600, 1644, 1285, 1152, 147.84, 145.46, 141.65, 135.94, 131.04, 130.35, 129.67, 129.23,
874, 692, 535; ESI-mass m/z: 494 (M+ + 1). HRMS (ESI) calc. for 128.77, 128.30, 128.00, 127.33, 126.85, 124.97, 124.21, 113.49,
C
31H19N5NaO2 [M+ + Na] 516.14364, found: 516.14363.
113.22, 110.55, 73.74, 58.95, 53.00, 13.06. IR (KBr, cmꢁ1): 3428,
3320, 3120, 1732, 1712, 1615, 1580, 1263, 1164, 1107, 999, 872,
752, 620, 533; ESI-mass m/z: 584 (M+ + 2Na).
20-Amino-5-chloro-60-(4-chlorophenyl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5h)
1
Ethyl 20-amino-5-chloro-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carboxylate (5l)
White solid; mp 200–202 ꢀC. H NMR (400 MHz, DMSO-d6) d
10.73 (s, 1H), 8.24 (s, 1H), 7.66 (s, 2H), 7.62–7.59 (m, 3H), 7.44
1
(d, J ¼ 8.6 Hz, 2H), 7.37 (t, J ¼ 7.6 Hz, 2H), 7.30 (t, J ¼ 7.3 Hz, White solid; mp 226–228 ꢀC. H NMR (400 MHz, DMSO-d6) d
1H), 7.19 (d, J ¼ 8.5 Hz, 4H), 6.70 (d, J ¼ 8.3 Hz, 1H). 13C NMR 10.33 (s, 1H), 8.08 (s, 2H), 8.05 (s, 1H), 7.63 (d, J ¼ 7.4 Hz, 2H),
(101 MHz, DMSO-d6) d 176.62, 160.72, 148.48, 146.56, 141.17, 7.43 (d, J ¼ 1.8 Hz, 1H), 7.33 (ddd, J ¼ 14.4, 10.8, 4.9 Hz, 6H),
135.94, 132.15, 130.12, 129.94, 129.87, 129.41, 129.23, 128.77, 7.20 (d, J ¼ 7.3 Hz, 2H), 7.14 (dd, J ¼ 8.2, 2.0 Hz, 1H), 6.55 (d, J ¼
128.48, 126.72, 126.07, 125.56, 124.36, 117.75, 112.34, 111.73, 8.2 Hz, 1H), 3.86–3.69 (m, 2H), 0.75 (t, J ¼ 7.1 Hz, 3H). 13C NMR
55.74, 53.52. IR (KBr, cmꢁ1): 3411, 3382, 3256, 3190, 2200, 1728, (101 MHz, DMSO-d6) d 178.22, 167.41, 160.61, 148.43, 146.04,
1685, 1646, 1476, 1299, 1155, 1013, 859, 762, 558, 450; ESI-mass 141.81, 136.18, 130.94, 130.22, 129.80, 129.35, 128.89, 128.77,
m/z: 527 (M++1). HRMS (ESI) calc. for C27H17Cl2N6O2 [M+ + 1] 128.59, 127.90, 126.15, 125.54, 124.78, 114.06, 110.60, 74.29,
527.07900, found: 527.08002.
59.55, 53.62, 13.63. IR (KBr, cmꢁ1): 3404, 3297, 3125, 1729, 1697,
1674, 1616, 1529, 1429, 1366, 1223, 1084, 965, 765, 695, 622,
509; ESI-mass m/z: 540 (M+ + 2Na).
20-Amino-5-bromo-60-(4-chlorophenyl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5i)
1
Ethyl 20-amino-5-uoro-2-oxo-60-phenyl-50-(4-phenyl-1H-1,2,3-
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carboxylate (5m)
White solid; mp 192–194 ꢀC. H NMR (400 MHz, DMSO-d6) d
10.74 (s, 1H), 8.24 (s, 1H), 7.69 (d, J ¼ 15.1 Hz, 3H), 7.61 (d, J ¼
1
7.5 Hz, 2H), 7.44 (d, J ¼ 8.5 Hz, 2H), 7.38 (t, J ¼ 7.5 Hz, 2H), 7.35– White solid; mp 216–218 ꢀC. H NMR (400 MHz, DMSO-d6) d
7.26 (m, 2H), 7.20 (d, J ¼ 8.4 Hz, 2H), 6.66 (d, J ¼ 8.3 Hz, 1H). 13
C
10.21 (s, 1H), 8.07 (s, 2H), 8.00 (s, 1H), 7.63 (d, J ¼ 7.4 Hz, 2H),
NMR (101 MHz, DMSO-d6) d 176.50, 160.71, 148.51, 146.55, 7.41–7.24 (m, 7H), 7.19 (d, J ¼ 7.2 Hz, 2H), 6.92 (td, J ¼ 9.5, 2.6
141.55, 135.93, 132.94, 132.49, 129.93, 129.88, 129.42, 128.77, Hz, 1H), 6.52 (dd, J ¼ 8.4, 4.3 Hz, 1H), 3.86–3.68 (m, 2H), 0.74 (t,
128.48, 125.56, 124.38, 117.76, 114.37, 112.31, 112.23, 100.00, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) d 178.41, 167.48,
55.75, 53.46. IR (KBr, cmꢁ1): 3432, 3392, 3308, 3258, 2206, 1744, 162.91, 160.58, 159.84, 157.49, 148.35, 146.00, 139.10, 135.87,
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130.91, 130.25, 129.85, 129.33, 128.89, 128.55, 127.88, 125.53, 125.59, 124.83, 124.36, 56.50, 55.77. IR (KBr, cmꢁ1): 3379, 3318,
124.74, 115.20, 114.97, 114.26, 112.56, 112.32, 109.89, 109.81, 3287, 2199, 1728, 1685, 1642, 1599, 1477, 1297, 1157, 1011, 818,
74.37, 60.25, 59.48, 53.83, 13.61. IR (KBr, cmꢁ1): 3382, 3210, 725, 558; ESI-mass m/z: 570 (M+), 572 (M+ + 2).
1716, 1698, 1483, 1368, 1297, 1219, 1104, 997, 880, 766, 695,
590; ESI-mass m/z: 524 (M+ + 2Na).
Ethyl 20-amino-5-bromo-60-(4-chlorophenyl)-2-oxo-50-(4-
phenyl-1H-1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-
carboxylate (5r)
20-Amino-5-bromo-60-(4-bromophenyl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5n)
1
White solid; mp 238–240 ꢀC. H NMR (400 MHz, DMSO-d6) d
1
White solid; mp 194–196 ꢀC. H NMR (400 MHz, DMSO-d6) d 10.33 (s, 1H), 8.08 (s, 2H), 8.05 (s, 1H), 7.64 (d, J ¼ 7.7 Hz, 2H),
10.72 (s, 1H), 8.24 (s, 1H), 7.70 (s, 1H), 7.65 (s, 2H), 7.59 (dd, J ¼ 7.55 (s, 1H), 7.38 (dd, J ¼ 12.5, 8.1 Hz, 4H), 7.29 (dd, J ¼ 15.1, 7.9
12.3, 8.2 Hz, 4H), 7.37 (t, J ¼ 7.5 Hz, 2H), 7.30 (dd, J ¼ 11.5, 5.7 Hz, 2H), 7.19 (d, J ¼ 8.5 Hz, 2H), 6.50 (d, J ¼ 8.2 Hz, 1H), 3.86–
Hz, 2H), 7.12 (d, J ¼ 8.5 Hz, 2H), 6.65 (d, J ¼ 8.3 Hz, 1H). 13C 3.69 (m, 2H), 0.75 (t, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO-
NMR (101 MHz, DMSO-d6) d 175.39, 159.64, 147.51, 145.49, d6) d 177.38, 166.77, 159.93, 146.84, 145.63, 141.65, 135.80,
140.50, 131.87, 131.42, 131.07, 128.96, 128.88, 128.34, 127.79, 135.12, 131.10, 129.60, 129.16, 128.79, 128.49, 128.09, 128.07,
127.71, 124.51, 123.74, 123.31, 116.68, 113.28, 111.25, 111.15, 126.93, 125.01, 124.11, 113.89, 113.25, 110.59, 73.72, 58.99,
54.68, 52.40. IR (KBr, cmꢁ1): 3375, 3308, 3186, 2200, 1730, 1605, 53.00, 13.06. IR (KBr, cmꢁ1): 3366, 3269, 3188, 1720, 1705, 1620,
1474, 1424, 1297, 1089, 888, 763, 638, 541, 478; ESI-mass m/z: 1473, 1404, 1298, 1225, 844, 722, 615, 508, 411; ESI-mass m/z:
615 (M+), 617 (M+ + 2).
617 (M+), 619 (M+ + 2).
Ethyl 20-amino-60-(4-chlorophenyl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carboxylate (5o)
20-Amino-60-(4-bromophenyl)-2-oxo-50-(4-phenyl-1H-1,2,3-
triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5s)
1
White solid; mp 202–204 ꢀC. 1H NMR (400 MHz, CDCl3) d 10.17 White solid; mp 200–202 ꢀC. H NMR (400 MHz, DMSO-d6) d
(s, 1H), 8.03 (s, 2H), 7.83 (s, 1H), 7.60 (d, J ¼ 7.5 Hz, 2H), 7.43– 10.58 (s, 1H), 8.16 (s, 1H), 7.58 (t, J ¼ 8.5 Hz, 6H), 7.43–7.32 (m,
7.26 (m, 6H), 7.17 (d, J ¼ 8.5 Hz, 2H), 7.10 (t, J ¼ 7.6 Hz, 1H), 6.97 3H), 7.28 (t, J ¼ 7.2 Hz, 1H), 7.12 (dd, J ¼ 14.0, 8.0 Hz, 3H), 6.96
(t, J ¼ 7.5 Hz, 1H), 6.53 (d, J ¼ 7.6 Hz, 1H), 3.83–3.67 (m, 2H), (t, J ¼ 7.5 Hz, 1H), 6.68 (d, J ¼ 7.7 Hz, 1H). 13C NMR (101 MHz,
0.71 (t, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) d 182.91, DMSO-d6) d 176.25, 160.16, 147.68, 145.89, 141.74, 131.58,
172.30, 165.16, 151.72, 150.80, 147.66, 140.33, 138.69, 134.98, 129.56, 129.43, 129.41, 129.34, 128.78, 128.39, 128.11, 125.22,
134.37, 134.09, 133.84, 133.69, 133.55, 133.33, 133.02, 130.30, 124.96, 124.17, 123.70, 122.11, 117.25, 112.56, 109.69, 79.06,
129.30, 126.95, 120.02, 113.99, 79.49, 64.17, 58.05, 18.33. IR 55.75, 52.63. IR (KBr, cmꢁ1): 3360, 3321, 3195, 2200, 1721, 1670,
(KBr, cmꢁ1): 3343, 3200, 1710, 1619, 1534, 1365, 1297, 1258, 1605, 1421, 1397, 1288, 1156, 1032, 885, 750, 684, 616, 471; ESI-
1183, 1015, 921, 836, 758, 694545; ESI-mass m/z: 540 (M+ + 1).
mass m/z: 537 (M+ + 1), 538 (M+ + 2).
Ethyl 20-amino-5-chloro-60-(4-chlorophenyl)-2-oxo-50-(4-
phenyl-1H-1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-
20-Amino-60-(4-chlorophenyl)-1-methyl-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5t)
carboxylate (5p)
1
White solid; mp 228–230 ꢀC. H NMR (400 MHz, DMSO-d6) d
1
White solid; mp 220–222 ꢀC. H NMR (400 MHz, DMSO-d6) d 8.14 (s, 1H), 7.64 (s, 2H), 7.57 (d, J ¼ 7.6 Hz, 2H), 7.43 (d, J ¼ 8.2
10.31 (s, 1H), 8.07 (s, 1H), 8.04 (s, 1H), 7.63 (d, J ¼ 7.6 Hz, 2H), Hz, 3H), 7.35 (t, J ¼ 7.5 Hz, 2H), 7.31–7.12 (m, 4H), 7.02 (t, J ¼ 7.5
7.46–7.33 (m, 5H), 7.29 (t, J ¼ 7.3 Hz, 1H), 7.18 (d, J ¼ 8.5 Hz, Hz, 1H), 6.90 (d, J ¼ 7.8 Hz, 1H), 3.10 (s, 3H). 13C NMR (101
2H), 7.13 (dd, J ¼ 8.2, 1.7 Hz, 1H), 6.54 (d, J ¼ 8.2 Hz, 1H), 3.84– MHz, DMSO-d6) d 174.24, 159.86, 147.11, 145.42, 142.71, 134.86,
3.69 (m, 2H), 0.74 (t, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO- 129.22, 128.88, 128.71, 128.27, 128.18, 127.89, 127.61, 127.46,
d6) d 178.06, 167.35, 160.50, 147.42, 146.19, 141.82, 140.52, 124.47, 124.35, 123.08, 122.27, 116.63, 111.89, 108.20, 54.79,
136.01, 135.68, 130.17, 129.73, 129.37, 129.07, 128.82, 128.67, 51.62, 26.02. IR (KBr, cmꢁ1): 3382, 3311, 3180, 2202, 1697, 1646,
128.65, 126.17, 125.59, 124.83, 124.68, 114.49, 110.61, 74.29, 1610, 1491, 1417, 1299, 1128, 836, 689, 543, 488; ESI-mass m/z:
59.55, 53.62, 13.63. IR (KBr, cmꢁ1): 3262, 3188, 3145, 1724, 1702, 506 (M+), 508 (M+ + 2).
1620, 1524, 1475, 1368, 1298, 1166, 898, 762, 560; ESI-mass m/z:
575 (M+ + 1), 576 (M+ + 2).
20-Amino-60-(4-chlorophenyl)-1-methyl-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5u)
20-Amino-60-(4-bromophenyl)-5-chloro-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5q)
1
White solid; mp 226–228 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.10 (s, 2H), 7.83 (s, 1H), 7.59 (d, J ¼ 7.6 Hz, 2H), 7.39 (dt, J ¼
1
White solid; mp 174–176 ꢀC. H NMR (400 MHz, DMSO-d6) d 18.0, 5.6 Hz, 5H), 7.28 (t, J ¼ 7.2 Hz, 1H), 7.18 (t, J ¼ 7.0 Hz, 3H),
10.71 (s, 1H), 7.64 (s, 2H), 7.59 (dd, J ¼ 12.6, 7.9 Hz, 5H), 7.37 (t, J 7.06 (t, J ¼ 7.5 Hz, 1H), 6.68 (d, J ¼ 7.7 Hz, 1H), 5.47–5.37 (m,
¼ 7.6 Hz, 2H), 7.30 (t, J ¼ 7.2 Hz, 1H), 7.19 (dd, J ¼ 8.3, 1.9 Hz, 1H), 4.92 (d, J ¼ 17.2 Hz, 1H), 4.83 (d, J ¼ 10.3 Hz, 1H), 4.24 (dd, J
1H), 7.12 (d, J ¼ 8.5 Hz, 2H), 6.70 (d, J ¼ 8.3 Hz, 1H). 13C NMR ¼ 16.1, 4.5 Hz, 1H), 3.91 (dd, J ¼ 16.1, 5.8 Hz, 1H), 3.80–3.62 (m,
(101 MHz, DMSO-d6) d 176.61, 160.73, 146.58, 141.19, 132.16, 2H), 0.65 (t, J ¼ 7.0 Hz, 3H). 13C NMR (101 MHz, DMSO-d6) d
130.13, 130.04, 129.96, 129.42, 128.87, 128.78, 126.73, 126.08, 176.24, 167.38, 160.50, 147.26, 146.32, 143.33, 135.69, 133.15,
19428 | RSC Adv., 2014, 4, 19422–19432
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132.05, 130.18, 129.63, 129.29, 129.11, 129.04, 128.68, 128.58, 7.18 (m, 2H), 7.10 (d, J ¼ 8.6 Hz, 1H), 6.73 (d, J ¼ 8.3 Hz, 1H). 13
C
125.62, 124.59, 124.41, 123.03, 117.77, 114.85, 108.78, 74.50, NMR (101 MHz, DMSO-d6) d 176.79, 160.91, 149.50, 146.49,
59.31, 52.83, 42.62, 13.96. IR (KBr, cmꢁ1): 3388, 3318, 3180, 141.23, 133.78, 132.43, 132.37, 130.11, 129.99, 129.37, 128.82,
2214, 1692, 1656, 1618, 1498, 1425, 1292, 1120, 825, 672, 540, 128.69, 128.59, 128.56, 128.36, 128.09, 127.60, 127.02, 126.75,
476; ESI-mass m/z: 581 (M+ + 2).
126.04, 125.53, 124.62, 124.34, 117.86, 112.26, 111.76, 55.81,
53.63. IR (KBr, cmꢁ1): 3308, 3184, 2197, 1727, 1679, 1640, 1598,
1477, 1301, 1230, 1199, 981, 820, 692, 560; ESI-mass m/z: 543
(M+ + 1), 544 (M+ + 2).
1-Allyl-20-amino-60-(4-bromophenyl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5v)
1
White solid; mp 220–222 ꢀC. H NMR (400 MHz, DMSO-d6) d
1-Allyl-20-amino-60-(naphthalen-2-yl)-2-oxo-50-(4-phenyl-1H-
8.15 (s, 1H), 7.66 (s, 2H), 7.62–7.53 (m, 4H), 7.48 (d, J ¼ 7.3 Hz,
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5z)
1H), 7.35 (t, J ¼ 7.5 Hz, 2H), 7.28 (t, J ¼ 7.2 Hz, 1H), 7.20 (t, J ¼
1
7.7 Hz, 1H), 7.11 (d, J ¼ 8.6 Hz, 2H), 7.04 (t, J ¼ 7.5 Hz, 1H), 6.80 White solid; mp 212–214 ꢀC. H NMR (400 MHz, DMSO-d6) d
(d, J ¼ 7.8 Hz, 1H), 5.75–5.66 (m, 1H), 5.09–4.96 (m, 2H), 4.27 (s, 8.16 (s, 1H), 7.95 (s, 1H), 7.86 (d, J ¼ 7.8 Hz, 1H), 7.82 (d, J ¼ 8.5
2H). 13C NMR (101 MHz, DMSO-d6) d 174.51, 160.26, 147.94, Hz, 2H), 7.68 (s, 2H), 7.60–7.47 (m, 5H), 7.31 (t, J ¼ 7.5 Hz, 2H),
146.01, 142.22, 131.60, 130.95, 129.63, 129.38, 128.77, 128.59, 7.27–7.18 (m, 2H), 7.06 (t, J ¼ 7.8 Hz, 2H), 6.81 (d, J ¼ 7.8 Hz,
128.31, 128.13, 125.07, 124.99, 124.26, 123.70, 122.84, 117.16, 1H), 5.72 (ddd, J ¼ 15.2, 9.7, 4.6 Hz, 1H), 5.04 (dd, J ¼ 13.9, 6.6
116.38, 112.22, 109.35, 79.05, 55.46, 52.25, 41.79. IR (KBr, Hz, 2H), 4.29 (s, 2H). 13C NMR (101 MHz, DMSO-d6) d 174.67,
cmꢁ1): 3473, 3327, 3140, 2199, 1709, 1606, 1359, 1229, 1198, 160.43, 148.83, 145.91, 142.28, 133.19, 131.87, 131.00, 128.79,
1073, 938, 830, 762, 691, 583, 516; ESI-mass m/z: 576 (M+), 578 128.72, 128.24, 128.03, 127.94, 127.78, 127.50, 127.02, 126.47,
(M+ + 2).
125.03, 124.94, 123.96, 123.68, 122.83, 117.26, 116.38, 115.03,
112.13, 109.34, 79.06, 55.53, 52.33. IR (KBr, cmꢁ1): 3475, 3321,
3175, 2197, 1710, 1648, 1487, 1465, 1438, 1407, 1357, 1303,
1196, 888, 759, 515, 477; ESI-mass m/z: 549 (M+ + 1).
Ethyl 20-amino-5-bromo-60-(4-bromophenyl)-2-oxo-50-(4-
phenyl-1H-1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-
carboxylate (5w)
1
Ethyl 20-amino-60-(4-bromophenyl)-5-chloro-2-oxo-50-(4-
phenyl-1H-1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-
carboxylate (5aa)
White solid; mp 242–244 ꢀC. H NMR (400 MHz, DMSO-d6) d
10.33 (s, 1H), 8.08 (s, 2H), 8.05 (s, 1H), 7.64 (d, J ¼ 7.6 Hz, 2H),
7.54 (d, J ¼ 8.7 Hz, 3H), 7.38 (t, J ¼ 7.5 Hz, 2H), 7.29 (dd, J ¼ 15.3,
1
8.2 Hz, 2H), 7.11 (d, J ¼ 8.4 Hz, 2H), 6.50 (d, J ¼ 8.2 Hz, 1H), White solid; mp 230–232 ꢀC. H NMR (400 MHz, DMSO-d6) d
3.86–3.69 (m, 2H), 0.75 (t, J ¼ 7.1 Hz, 3H). 13C NMR (101 MHz, 10.31 (s, 1H), 8.08 (s, 2H), 8.05 (s, 1H), 7.63 (d, J ¼ 7.6 Hz, 2H),
DMSO-d6) d 177.36, 166.76, 159.91, 146.93, 145.61, 141.63, 7.54 (d, J ¼ 8.2 Hz, 2H), 7.44 (s, 1H), 7.38 (t, J ¼ 7.5 Hz, 2H), 7.30
135.77, 131.41, 131.10, 129.57, 129.32, 128.80, 128.45, 128.08, (t, J ¼ 7.2 Hz, 1H), 7.12 (t, J ¼ 9.7 Hz, 3H), 6.54 (d, J ¼ 8.2 Hz,
126.92, 125.00, 124.10, 123.97, 113.86, 113.25, 110.58, 73.70, 1H), 3.83–3.70 (m, 2H), 0.74 (t, J ¼ 7.0 Hz, 3H). 13C NMR (101
58.99, 52.99, 13.05. IR (KBr, cmꢁ1): 3379, 3271, 3140, 1723, 1700, MHz, DMSO-d6) d 177.47, 166.76, 159.90, 146.91, 145.61, 141.23,
1618, 1526, 1474, 1298, 1222, 1108, 828, 697, 547; ESI-mass m/z: 135.42, 131.41, 129.58, 129.31, 128.79, 128.45, 128.24, 128.07,
664 (M+ + 2).
125.58, 125.00, 124.25, 124.10, 123.97, 113.88, 110.02, 79.06,
58.96, 53.03, 13.05. IR (KBr, cmꢁ1): 3359, 3269, 3142, 1722, 1702,
1619, 1525, 1475, 1385, 1295, 1103, 832, 761, 489; ESI-mass m/z:
619 (M+ + 2).
20-Amino-5-bromo-60-(naphthalen-2-yl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5x)
1
White solid; mp 240–242 ꢀC. H NMR (400 MHz, DMSO-d6) d
10.75 (s, 1H), 8.25 (s, 1H), 7.95 (s, 1H), 7.85 (dd, J ¼ 16.0, 7.9 Hz,
General procedure for synthesis of 7
3H), 7.72 (d, J ¼ 1.2 Hz, 1H), 7.68 (s, 2H), 7.62–7.50 (m, 4H), 7.33 A dried, 10 mL round-bottomed ask was charged with phe-
(t, J ¼ 7.1 Hz, 3H), 7.26 (t, J ¼ 7.2 Hz, 1H), 7.10 (d, J ¼ 8.8 Hz, nacyltriazole (1.0 mmol), substituted aldehyde (1.0 mmol), and
1H), 6.68 (d, J ¼ 8.3 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) d active methylene compound (1.0 mmol), and 20 mol% of InCl3
176.66, 160.92, 149.52, 146.50, 141.63, 133.78, 132.94, 132.71, was added to the reaction mixture and heated in an oil bath at
132.43, 130.00, 129.37, 128.81, 128.74, 128.70, 128.57, 128.36, 100 ꢀC for the stipulated time. Aer completion of the reaction
128.09, 127.59, 127.03, 125.54, 124.63, 124.36, 117.85, 114.39, (monitored by TLC), ethanol (2 mL) was added to the reaction
112.26, 55.87, 53.59. IR (KBr, cmꢁ1): 3317, 3185, 2198, 1722, mixture. The products appeared as solids, by trituration with
1676, 1640, 1598, 1474, 14410, 1301, 1201, 1116, 979, 859, 762, ethanol, and were ltered and washed with another 2 mL of
473; ESI-mass m/z: 588 (M+ + 2).
EtOH to remove other impurities. Finally, the products 7 were
dried and were pure enough for the spectral investigations.
20-Amino-5-chloro-60-(naphthalen-2-yl)-2-oxo-50-(4-phenyl-1H-
1,2,3-triazol-1-yl)spiro[indoline-3,40-pyran]-30-carbonitrile (5y)
2-Amino-4-(4-nitrophenyl)-6-phenyl-5-(4-phenyl-1H-1,2,3-
1
triazol-1-yl)-4H-pyran-3-carbonitrile (7a)
White solid; mp 218–220 ꢀC. H NMR (400 MHz, DMSO-d6) d
1
10.75 (s, 1H), 8.26 (s, 1H), 7.95 (s, 1H), 7.84 (dd, J ¼ 15.1, 8.1 Hz, White solid; mp 192–194 ꢀC. H NMR (400 MHz, DMSO-d6) d
3H), 7.69 (s, 2H), 7.64–7.50 (m, 5H), 7.33 (t, J ¼ 7.4 Hz, 2H), 7.29– 8.48 (s, 1H), 8.20 (d, J ¼ 8.7 Hz, 2H), 7.67 (d, J ¼ 7.2 Hz, 2H), 7.58
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(d, J ¼ 8.7 Hz, 2H), 7.44–7.27 (m, 8H), 7.25–7.19 (m, 2H), 5.00 (s, 115.97, 56.68, 43.10. IR (KBr, cmꢁ1): 3450, 3313, 2204, 1690,
1H). 13C NMR (101 MHz, DMSO-d6) d 160.00, 147.45, 147.22, 1656, 1600, 1489, 1409, 1263, 1147, 1094, 1073, 933, 837, 760,
146.84, 130.83, 130.23, 130.11, 129.77, 129.40, 128.94, 128.70, 690, 507, 406; ESI-mass m/z: 531 (M+ + 2). HRMS (ESI) calc. for
127.99, 125.59, 124.44, 123.55, 119.50, 114.92, 56.24, 43.38. IR
(KBr, cmꢁ1): 3473, 3360, 2183, 1688, 1642, 1611, 1521, 1455,
1347, 1263, 1220, 1148, 864, 764, 693, 529, 480; ESI-mass m/z:
463 (M++1). HRMS (ESI) calc. for C26H18N6NaO3 [M+ + Na]
485.13381, found: 485.11270.
C
26H18BrClN5O [M+ + 1] 530.03833, found: 530.03851.
2-Amino-4,6-bis(4-chlorophenyl)-5-(4-phenyl-1H-1,2,3-triazol-
1-yl)-4H-pyran-3-carbonitrile (7f)
1
White solid; mp 216–218 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.51 (s, 1H), 7.70 (d, J ¼ 7.4 Hz, 2H), 7.45–7.25 (m, 12H), 7.20 (d,
J ¼ 8.6 Hz, 2H), 4.82 (s, 1H). 13C NMR (101 MHz, DMSO-d6) d
159.76, 146.88, 145.54, 140.63, 135.37, 132.73, 130.26, 130.23,
129.81, 129.42, 129.21, 129.16, 129.06, 128.71, 125.61, 123.37,
119.64, 116.03, 56.75, 43.03. IR (KBr, cmꢁ1): 3452, 3312, 2203,
1690, 1655, 1599, 1491, 1410, 1263, 1148, 1092, 914, 836, 761,
510, 420; ESI-mass m/z: 485 (M+).
2-Amino-6-(4-chlorophenyl)-4-(4-nitrophenyl)-5-(4-phenyl-1H-
1,2,3-triazol-1-yl)-4H-pyran-3-carbonitrile (7b)
1
White solid; mp 188–190 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.53 (s, 1H), 8.19 (d, J ¼ 8.7 Hz, 2H), 7.69 (d, J ¼ 7.3 Hz, 2H), 7.58
(d, J ¼ 8.7 Hz, 2H), 7.48–7.37 (m, 6H), 7.32 (t, J ¼ 7.3 Hz, 1H),
7.22 (d, J ¼ 8.6 Hz, 2H), 5.01 (s, 1H). 13C NMR (101 MHz, DMSO-
d6) d 158.85, 148.15, 146.40, 145.90, 145.03, 134.45, 129.15,
128.78, 128.73, 128.33, 128.04, 127.98, 127.66, 124.57, 123.37,
122.33, 118.36, 114.32, 55.15, 42.23. IR (KBr, cmꢁ1): 3461, 3320,
2191, 1684, 1644, 1598, 1518, 1405, 1348, 1263, 1148, 1097, 818,
740, 695, 509, 462; ESI-mass m/z: 498 (M+ + 2). HRMS (ESI) calc.
for C26H16ClN6O3 [M+ ꢁ 1] 495.09724, found: 495.09705.
2-Amino-6-(4-bromophenyl)-4-(4-nitrophenyl)-5-(4-phenyl-1H-
1,2,3-triazol-1-yl)-4H-pyran-3-carbonitrile (7g)
White solid; mp 194-194 ꢀC. 1H NMR (400 MHz, DMSO-d6) d
8.49 (s, 1H), 8.17 (d, J ¼ 8.0 Hz, 2H), 7.67 (d, J ¼ 7.1 Hz, 2H),
7.61–7.48 (m, 4H), 7.45–7.27 (m, 5H), 7.14 (d, J ¼ 8.0 Hz, 2H),
4.99 (s, 1H). 13C NMR (101 MHz, DMSO) d 159.84, 149.02,
147.44, 147.02, 146.31, 130.04, 129.98, 129.88, 129.80, 129.46,
129.34, 128.87, 125.62, 124.41, 124.35, 123.35, 119.47, 115.16,
56.19, 43.22. IR (KBr, cmꢁ1): 3379, 3318, 3287, 2199, 1728, 1685,
1642, 1477, 1223, 818, 725, 558; ESI-mass m/z: 542 (M+ + 2).
2-Amino-4-(4-chlorophenyl)-6-phenyl-5-(4-phenyl-1H-1,2,3-
triazol-1-yl)-4H-pyran-3-carbonitrile (7c)
1
White solid; mp 214–216 ꢀC. H NMR (400 MHz, DMSO-d6) d
7.68 (d, J ¼ 7.6 Hz, 2H), 7.44–7.23 (m, 13H), 7.20 (d, J ¼ 7.5 Hz,
2H), 4.81 (s, 1H). 13C NMR (101 MHz, DMSO-d6) d 159.31,
146.17, 146.08, 140.24, 132.11, 130.10, 129.78, 129.74, 129.63,
128.81, 128.59, 128.33, 128.06, 127.39, 125.01, 122.96, 119.11,
115.07, 56.22, 42.58. IR (KBr, cmꢁ1): 3456, 3335, 2193, 1693,
1654, 1599, 1429, 1259, 1142, 1088, 979, 843, 762, 633, 508, 420;
ESI-mass m/z: 453 (M+ + 2). HRMS (ESI) calc. for C26H19ClN5O
[M+ + 1] 452.12781, found: 452.12866.
2-Amino-6-(4-bromophenyl)-4-(4-chlorophenyl)-5-(4-phenyl-
1H-1,2,3-triazol-1-yl)-4H-pyran-3-carbonitrile (7h)
1
White solid; mp 214–216 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.47 (s, 1H), 7.68 (d, J ¼ 6.8 Hz, 2H), 7.52 (d, J ¼ 7.7 Hz, 2H),
7.47–7.20 (m, 9H), 7.12 (d, J ¼ 7.6 Hz, 2H), 4.81 (s, 1H). 13C NMR
(101 MHz, DMSO) d 159.68, 146.93, 145.72, 140.43, 132.78,
131.96, 130.22, 130.06, 130.00, 129.51, 129.47, 129.15, 128.83,
125.59, 124.18, 123.30, 119.67, 115.85, 56.77, 42.93. IR (KBr,
cmꢁ1): 3366, 3188, 1720, 1705, 1696, 1620, 1473, 1298, 1162,
964, 844, 783, 695, 508, 411; ESI-mass m/z: 529 (M+).
2-Amino-4-(4-bromophenyl)-6-phenyl-5-(4-phenyl-1H-1,2,3-
triazol-1-yl)-4H-pyran-3-carbonitrile (7d)
1
White solid; mp 212–214 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.46 (s, 1H), 7.69 (d, J ¼ 7.6 Hz, 2H), 7.51 (d, J ¼ 8.3 Hz, 2H),
7.44–7.28 (m, 8H), 7.21 (t, J ¼ 7.2 Hz, 4H), 4.80 (s, 1H). 13C NMR
(101 MHz, DMSO-d6) d 159.86, 146.74, 146.65, 141.22, 132.08,
130.68, 130.55, 130.32, 130.28, 129.40, 128.91, 128.65, 127.95,
125.58, 123.52, 121.29, 119.71, 115.53, 56.69, 43.19. IR (KBr,
cmꢁ1): 3458, 3335, 2195, 1694, 1656, 1601, 1486, 1260, 1143,
1030, 841, 690, 563; ESI-mass m/z: 495 (M+), 497 (M+ + 2). HRMS
(ESI) calc. for C26H19BrN5O [M+ + 1] 496.07730, found:
496.07687.
2-Amino-4-(4-bromophenyl)-6-(naphthalen-2-yl)-5-(4-phenyl-
1H-1,2,3-triazol-1-yl)-4H-pyran-3-carbonitrile (7i)
1
White solid; mp 224–226 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.51 (s, 1H), 7.95 (s, 1H), 7.90–7.77 (m, 3H), 7.66 (d, J ¼ 7.5 Hz,
2H), 7.58–7.48 (m, 4H), 7.27–7.40 (m, 5H), 7.24 (d, J ¼ 8.3 Hz,
2H), 7.07 (d, J ¼ 8.8 Hz, 1H), 4.85 (s, 1H). 13C NMR (101 MHz,
DMSO) d 158.88, 145.72, 145.49, 138.11, 131.43, 131.03, 129.48,
129.24, 128.31, 127.66, 127.56, 127.34, 127.17, 127.00, 126.96,
126.64, 126.35, 124.51, 123.41, 122.54, 120.22, 118.64, 114.84,
55.65, 42.14. IR (KBr, cmꢁ1): 3449, 3328, 2197, 1689, 1650, 1597,
1407, 1315, 1235, 1191, 1074, 968, 758, 689, 502, 482; ESI-mass
m/z: 547 (M+ + 2).
2-Amino-4-(4-bromophenyl)-6-(4-chlorophenyl)-5-(4-phenyl-
1H-1,2,3-triazol-1-yl)-4H-pyran-3-carbonitrile (7e)
1
White solid; mp 220–222 ꢀC. H NMR (400 MHz, DMSO-d6) d
8.52 (s, 1H), 7.70 (d, J ¼ 7.6 Hz, 2H), 7.51 (d, J ¼ 8.3 Hz, 2H), 7.41
(dd, J ¼ 7.8, 5.8 Hz, 4H), 7.36–7.29 (m, 3H), 7.21 (dd, J ¼ 8.3, 6.5
Hz, 4H), 4.81 (s, 1H). 13C NMR (101 MHz, DMSO-d6) d 159.76,
2-Amino-4,6-bis(4-bromophenyl)-5-(4-phenyl-1H-1,2,3-triazol-
1-yl)-4H-pyran-3-carbonitrile (7j)
1
146.89, 145.55, 141.06, 135.37, 132.08, 130.57, 130.26, 129.81, White solid; mp 218–220 ꢀC. H NMR (400 MHz, DMSO-d6) d
129.42, 129.20, 129.06, 128.71, 125.62, 123.36, 121.34, 119.64, 8.47 (s, 1H), 7.68 (d, J ¼ 7.7 Hz, 2H), 7.50 (dd, J ¼ 14.6, 7.9 Hz,
19430 | RSC Adv., 2014, 4, 19422–19432
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4H), 7.40 (t, J ¼ 7.4 Hz, 2H), 7.32 (t, J ¼ 7.3 Hz, 1H), 7.27 (s, 2H),
1991, 28, 1301; (d) T. Kohara, K. Fukunaga, M. Fujimura,
T. Hanano and H. Okabe, US Pat. 0052822, 2004.
7.20 (d, J ¼ 7.9 Hz, 2H), 7.12 (d, J ¼ 8.1 Hz, 2H), 4.79 (s, 1H). 13
C
NMR (101 MHz, DMSO) d 159.69, 146.94, 145.75, 140.87, 132.06,
131.96, 130.57, 130.07, 130.00, 129.51, 129.46, 128.83, 125.61,
124.19, 123.30, 121.37, 119.65, 115.79, 56.75, 43.03. IR (KBr,
cmꢁ1): 3453, 3335, 2201, 1685, 1659, 1591, 1488, 1413, 1261,
1225, 1077, 830, 761, 690, 581, 465; ESI-mass m/z: 574 (M+).
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Acknowledgements
One of the authors, J. Kamalraja, thanks the Council of Scien-
tic and Industrial Research (CSIR), New Delhi, India for the
research fellowship.
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manuscript have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
number CCDC 953661.†
19432 | RSC Adv., 2014, 4, 19422–19432
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