Unusual reactivity of 1-aminoanthraquinone in copper catalyzed multicomponent reaction with isatins and aryl alkynes: Synthesis and photophysical properties of regioisomeric fluorescent 3-spiroheterocyclic 2-oxindoles

Article abstract of DOI:10.1016/j.tet.2013.02.037

Unusual reactivity of 1-aminoanthraquinone with a number of isatins and aryl alkynes in a copper catalyzed multicomponent reaction afforded a novel, highly conjugated, and separable regioisomers of 3-spiroheterocyclic 2-oxindoles in excellent combined yield. Both the regioisomers exhibited considerable optical properties and found as fluorescence materials. Based on experimental observation, a plausible reaction mechanism has been proposed.

Full text of DOI:10.1016/j.tet.2013.02.037

Tetrahedron 69 (2013) 2891e2899
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Unusual reactivity of 1-aminoanthraquinone in copper catalyzed
multicomponent reaction with isatins and aryl alkynes: synthesis
and photophysical properties of regioisomeric fluorescent
3-spiroheterocyclic 2-oxindoles
,
b
Somasundharam Periyaraja a, Ponnusamy Shanmugam a , Asit Baran Mandal ,
*
,
Thiyagarajan Senthil Kumar c, Perumal Ramamurthy c
*
a Organic Chemistry Division, Council of Scientific and Industrial Research (CSIR), Central Leather Research Institute (CLRI), Adyar, Chennai 600020,
India
b Chemical Laboratory, Council of Scientific and Industrial Research (CSIR), Central Leather Research Institute (CLRI), Adyar, Chennai 600020, India
c National Centre for Ultrafast Processes (NCUFP), University of Madras, Chennai 600113, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Unusual reactivity of 1-aminoanthraquinone with a number of isatins and aryl alkynes in a copper
catalyzed multicomponent reaction afforded a novel, highly conjugated, and separable regioisomers of 3-
spiroheterocyclic 2-oxindoles in excellent combined yield. Both the regioisomers exhibited considerable
optical properties and found as fluorescence materials. Based on experimental observation, a plausible
reaction mechanism has been proposed.
Received 20 September 2012
Received in revised form 14 January 2013
Accepted 11 February 2013
Available online 15 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Multicomponent reaction
Copper catalyst
Spirocycle-2-oxindole
Photophysical properties
Fluorescent materials
1. Introduction
emerged as potential fluorescent materials.15 With this point of view,
recently we have reported16 the synthesis of highly luminescent
Multicomponent reactions1,2 (MCRs) are regarded as powerful
method for the rapid construction of complex molecular architec-
tures in a one-pot and economical mode. Particularly, this diversity
oriented3 MCRs have been found broad application in the discovery
of pharmaceutical lead structures. However, for the synthesis of
acyclic merocyanine dye analogue materials via a multicomponent
reaction using binary copper as a catalyst.17
Generally, coupling of an aldehyde, alkyne, and amine catalyzed
by Cu(I) salts is known as A3 coupling18 and its ketone analogue is
KA2 coupling19 and have been successfully utilized for the synthesis
of propargylamine derivatives. In continuation of our research work
in the synthesis of various 3-spirocyclic 2-oxindoles20 from Mor-
itaeBayliseHillman (MBH) adduct of isatin and to overcome the
materials with
p-conjugated systems, such as electrophores, chro-
mophores, and fluorophores have been used in the development of
novel electronics,4 photonics,5 and biophysical analysis,6 this ap-
proach is quite novel.7,8 Transition metal catalyzed9 MCRs for the
synthesis of quinolines and indoles have paved the way to diverse
classes of heterocycles.10 Significantly, 3-spiroheterocyclic 2-
oxindole cores have been found in a number of natural products,
such as alstonisine,11 tabernoxidine,12 and medicinally important
NITD 60913 (Fig. 1). In addition to the significant biological activities
of 3-spiroheterocyclic 2-oxindoles,14 these compounds have
* Corresponding authors. Tel.: þ91 44 24437129; fax: þ91 44 24911589; e-mail
addresses: shanmu196@rediffmail.com, shanmu196@gmail.com (P. Shanmugam).
Fig. 1. Natural products and anti-malarial drug with 3-spiro-oxindole core structures.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.037

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S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
limited synthesis of chromophoric 3-spiroheterocyclic 2-indolones,
a novel and efficient synthetic method has been developed by KA2
type coupling of 1-aminoanthraquinone, 1-methylisatin, and aryl
alkynes using copper as a catalyst (Scheme 1) and the details are
presented in this manuscript. Notably, unlike the role of amines in A3
or KA2 coupling reactions, 1-aminoanthraquinone demonstrated an
unusual reactivity to afford regioisomeric title compounds. This
method has an advantage, such as readily available substrates, mild
reaction condition, and simple column separation of regioisomers.
O
O
O
O
O
N
N
20 mol % CuCl(A),
O
20 mol % Cu(OTf)2(B)
H
+
2a
1a
+
HN
N
dry. toluene, reflux
N2, 120 ºC, 24 hr
67%
NH2
O
O
One-Pot
O
N
O
Violet 5a
Pink 4a
3a
Scheme 1. Synthesis of regioisomeric 3-spiroheterocyclic 2-oxindoles 4a and 5a.
2. Results and discussion
Initially, to a mixture of 1-methylisatin 1a (1 equiv), phenylacetyl-
ene 2a (1 equiv), and 1-aminoanthraquinone 3a (1.2 equiv) in dry
toluene, 20 mol % each of CuCl (A) and Cu(OTf)2 (B) catalysts was added
under nitrogen atmosphere and the reaction mixture was stirred at
120 ꢀC for 16 h (Scheme 1). In contradiction of previous report,16 the
reaction with 1-aminoanthraquinone as amine counterpart afforded
regioisomeric 3-spiroheterocyclic 2-oxidoles 4a and 5a in 32% and 35%
yield, respectively (Table 1, entry 1). The structure of compounds 4a
and 5a were assigned by analysis of spectroscopic and analytical data
(UVevis, FT-IR, 1H NMR, 13C NMR, and HRMS) and unambiguously
confirmed by a single crystal X-ray analysis (Fig. 2).21
Fig. 2. ORTEP diagram of compounds 4a and 5a.21
3 ꢀC/minute upto 120 ꢀC resulted in a significantly higher yield than
heating it on a preheated oil bath at 120 ꢀC. Further, reactions at
lower temperature (80 ꢀC) and shortening time (16 h) also provided
lower yields. However, all the cases, the ratio of the products was
found to be relatively constant. Thus, offer information about two
possible intermediates to propose a mechanism.
Table 1
Optimization of synthesis of 3-spiroheterocyclic 2-oxindoles 4a and 5a
To demonstrate the scope and limitation of the reaction, under
optimized condition, experiments with a number of substituted
isatins 1aeg, aryl alkynes 2aee, and 1-aminoanthraquinones 3a,b
have been carried out. All the reactions underwent smoothly and
provided corresponding both regioisomeric spiro heterocycles 4aei
and 5aei in excellent combined yield (Table 2). It has been ob-
served that N-methylisatin with electron withdrawing group at
fifth position of the aryl ring afforded better yield than those with
electron releasing group. Isatin gave a trace amount of product 5k
along with inseparable mixture. 5-Nitroisatin and 5-methylisatin
did not yield any product. Alkyne 2e gave only product 5j, pre-
sumably due to weak nucleophilicity. However, in contrary, the
reaction with 2-aminoanthraquinone found to be failed and affor-
ded inseparable complex mixture (Table 2, entry 12). The reaction
with 1,4-diaminoanthraquinone 3b gave only one product 5l. To
testify the reactions with other aryl amines, the reaction with 5-
aminoquinoline gave only imine as a product. The reaction with
8-aminoquinoline and 5-amino-1,4-napthoquinone22 gave in-
separable mixture. The reaction with and 9-aminoacridine did not
give any product and starting materials have been recovered.
Based on the isolated products 4a and 5a, a plausible mechanism
is proposed as illustrated in Scheme 2. Thus, for compound 4a, nu-
cleophilic addition of Cu-phenyl acetylide to imine A obtained from
isatin and 1-aminoanthraquinone to give propargylamine derivative
B. Activation of alkyne in B by Cu(II) followed by an intramolecular
FriedeleCrafts type cyclization to form cyclic intermediate C, which
upon aromatization affords 4a. For the other regioisomer 5a, it is
believed that initial Cu(I) catalyzed competitive nucleophilic addi-
tion of phenyl acetylide to isatin provide propargyl alcohol derivative
Entry
Ratio of 1a:2a:3a
Mole ratio of catalyst (A:B)
Yield of 4a:5a (%)
1
2
3
4
5
6
7
8
9
1:1:1.2
1:1.2:1
20:20
20:20
20:20
20:20
05:05
10:10
10:00
00:10
10:10
32:35
36:37
37:38
26:34a
16:35
39:42c
0
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
1:1.2:1.2
5:27
23:35b
a
Performed on a preheated oil bath.
Performed in air.
Optimized condition.
b
c
It should be noted that the reactivity of 1-aminoanthraquinone
in this reaction has been found completely altered and provided
unusual and unique 3-spiroheterocyclic 2-oxindoles in a one-pot
reaction. To optimize the synthesis of compounds 4a and 5a,
a number of experiments with change in number of mole equiva-
lent of reagents and catalysts have been carried out (Table 1).
Change of the reactant mole ratio as 1:1.2:1.2 and 10 mol % of each
CuCl/Cu(OTf)2 catalysts under nitrogen atmosphere, provided
compounds 4a and 5a in 81% combined yield and was found to be
optimized condition (Table 1, entry 6). Increasing the mole equiv-
alents of alkyne (1.5 equiv) and 1-aminoanthraquinone (1.5 equiv)
lead to decrease in the yield. The presence of both CuCl and
Cu(OTf)2 catalysts is important since absence of one of the catalysts
resulted lower yields of products (entries 7 and 8). It should be
noted that gradual increase of the reaction temperature by

S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
2893
Table 2
Synthesis of spiroheterocyclic compounds 4aei and 5ael
O
O
N
NH
H
O
O
O
N
N
O
F
5a
(II)
O
O
Cu
H
O
O
O
O
O
O
O
[Cu]
O
O
O
O
NH
O
O
O
O
O
O
O
O
O
O
H
H
H2N
N
N
HN
HN
O2N
O2N
O
-H2O
N
O
O
O
O
O
O
O
E
N
N
O
O
N
O
N
N
D
3a
O
5a
5b
4a
4b
2a
nucleophilic
Cu(I)Cl addition
O
O
O
O
O
H
H
O
N
N
HN
HN
I
I
N
1a
3a
N
N
O
O
N
N
-H2O
5c
5d
4c
4d
O
O
O
O
O
O
H
H
N
N
HN
HN
F3CO
Br
O
O
O
Cu(I)Cl
F3CO
Br
N
nucleophilic
addition
N
N
O
O
HN
N
N
O
5e
5f
N
4e
4f
O
O
2a
A
O
N
Cu(II)
O
B
O
O
O
H
H
N
N
HN
HN
F
F
O
O
N
N
O
O
N
N
O
O
5g
5h
4g
4h
HN
N
O
N
H
O
O
O
O
O
O
H
H
H
H2N
CF3
O
N
N
HN
N
O
OCH3
N
OCH3
4a
C
O
N
O
O
O
N
N
N
Scheme 2. Plausible mechanism for the formation of 4a and 5a.
4i
5i
5j
5l
2a
Entry
Isatin
Alkyne
Product(s)
Yielda (%)
3a
4a (12%) +
5a (62%)
D
A
a
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1a
1a
1a
1a
1g
1a
1a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2a
2a
2a
4a(39)
4b(42)
4c(38)
4d(40)
4e(39)
4f(38)
4g(35)
4h(33)
4i(34)
d
5a(42)
5b(45)
5c(40)
5d(42)
5e(46)
5f(45)
5g(39)
5h(40)
5i(38)
5j(42)
5k(trace)
d
120 ºC, 24 hr
1a
2a
3a
+
4a (48%)
5a (22%)
120 ºC, 24 hr
b
a. 10 mol % CuCl, 10 mol % Cu(OTf)2, Toluene, N2, 90 ºC, 2.5 hr;
b. 10 mol % CuCl, 10 mol % Cu(OTf)2, Toluene, N2, 120 ºC, 2.5hr
9
Scheme 3. Experimental support for the proposed mechanism.
10
11
12b
13c
d
the first experiment, N-methylisatin 1a and phenylacetylene 2a
were stirred at 90 ꢀC in the presence of binary Cu(I)/Cu(II) catalytic
system for 2.5 h. Then 1-aminoanthraquinone 3a was added and
refluxed for 24 h at 120 ꢀC afforded 4a as a minor and 5a as a major
product. It revealed that major part of the reaction was proceeded
through propargyl alcohol intermediate D (Scheme 2). In the other
experiment, N-methylisatin 1a and 1-aminoanthraquinone 3a were
refluxed at 120 ꢀC in the presence of binary Cu(I)/Cu(II) catalytic
system for 2.5 h. Then phenylacetylene 2a was added and refluxed
for 24 h at 120 ꢀC results 4a as a major and 5a as a minor product. It
revealed that major part of the reaction proceeded via imine in-
termediate A. However, in both the cases the combined yield is
lesser than the original reaction carried out in a one-pot manner
and both the isomers are formed but with altered product ratio.
Significantly, physical nature of compounds 4a (pink) and 5a
(violet) prompted us to evaluate their photophysical properties.
d
d
5l(46)
a
All the reactions were carried out using isatins (1.00 mmol, 1.0 equiv), alkynes
(1 mmol, 1.2 equiv), and amines (1 mmol, 1.2 equiv) with 10 mol % of each CuCl and
Cu(OTf)2 as catalysts.
b
The reaction was carried out with 2-aminoanthraquinone.
The reaction was carried out with 1,4-diaminoanthraquinone.
c
D. Simultaneous activation of alkyne and 3ꢀ-OH groups in D by Cu(II)
followed by reaction with 1-aminoanthraquinone to afford allene
intermediate E. Since copper coordination increases the electrophi-
licity of allene E, which then undergoes an intramolecular Frie-
deleCrafts type cyclization to intermediate F, which on
aromatization affords 5a.
To support the proposed mechanism, experiments with change
of order of addition of reagents have been carried out (Scheme 3). In

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S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
Thus, both compounds 4a and 5a showed UV-absorption maxima in
the visible region at 519 nm and 521 nm, respectively. Compound 4a
showed a 116 nm red shifted broad emission covering entire red
region (620e730 nm) with a maxima at 635 nm, whereas compound
5a showed dual emissive behavior of 30 nm red shifted orange-red
emission with an emission maxima at 551 nm and a broad hump
at 617 nm (Fig. 3). Further, the time correlated single photon
counting measurement revealed the fluorescence lifetime decay of
compound 4a is bi-exponential with lifetimes of 0.396 ns (92.63%)
and 6.47 ns (7.63%) while compound 5a as tri-exponential with
lifetimes of 0.751 ns (15.24%), 2.42 ns (37.67%) and 9.59 ns (47.09%)
(Fig. 3). However, lower quantum yields of 4a (0.02) and 5a (0.006)
have been measured using rhodamine 6G in ethanol as a reference.
Further, change of excitation wavelength did not improve the
quantum yield. The above data confirmed that compounds 4a and 5a
are possible fluorescent spirocyclic 2-oxindole dye materials.
aminoanthraquinone molecular absorption, which is shown in
Fig. 5(a). Hence 5a existing as a non conjugated but covalently
linked bichromophoric system since the emission at 551 nm cor-
responds to the locally excited state whereas the emission at
617 nm may be due to the anthraquinone moiety. However such
bichromophoric behavior is not observed in compound 4a because
of the extended
p-conjugation provided by the phenylacetylene
unit and hence the emission is solely due to the locally excited state
(charge transfer from the spirocycle ring donor to the anthraqui-
none acceptor, Fig. 4(a)).
NMI_Abs
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
4a
5a
AAQ_Abs
5a_Abs
5a_Ex_551 nm
5a_Ex_617 nm
4
6x10
5
0.10
0.12
0.10
0.08
0.06
8.0x10
6.0x10
4.0x10
5a_Abs
5a_Emi
4a_Abs
4a_Emi
4
4
4
4
4
5x10
4x10
3x10
2x10
400
500
600
700
0.08
0.06
0.04
0.02
0.00
500
600
700
5
5
5
Wavelength (nm)
Wavelength (nm)
(a)
(b)
2.0x10
Fig. 5. Absorption spectra of N-methylisatin (NMI), 1-aminoanthraquinone (AAQ), 5a
and excitation spectrum of 5a monitored at 551 nm and 617 nm (a) and diffused re-
flectance spectra of 4a and 5a (b).
1x10
0.0
0
800
400
500
600
700
800
400
500
600
700
Wavelength (nm)
Wavelength (nm)
To have a clear picture about the nature of the emitting species,
time resolved fluorescence studies were carried out using TCSPC
technique by exciting the sample at an excitation wavelength of
375 nm. Monitoring the fluorescence decay at 635 nm, compound
4a showed biexponential behavior with a lifetime of 0.396 ns (0.93)
and 6.47 ns (0.07). The longer component in fluorescence decay
(6.47 ns) is attributed to the LE state and the shorter component
(0.396 ns) may be due to the intramolecular hydrogen bonding
existing between carbonyl oxygen and secondary amine in the
anthraquinone moiety.
(a)
(b)
10000
Prompt
4a
5a
1000
100
10
1
1-Aminoanthraquinone and its derivatives are well known for
their radiationless deactivation process through intramolecular
hydrogen bonding in nonpolar/polar aprotic solvents and through
intermolecular hydrogen bonding with polar protic solvents.23 To
know the role of hydrogen bonding in the present study, we carried
out the time resolved fluorescence studies in non-polar and polar
protic solvents. In hexane compound 4a shows single exponential
behavior with a lifetime of 0.698 ns due to the radiationless de-
activation process provided by intramolecular hydrogen bonding,
similarly in methanol it shows single exponential behavior with
a lifetime of 0.318 ns due to the intermolecular hydrogen bonding
in methanol (Table 3). The above observation reveals that both the
intramolecular and intermolecular hydrogen bonding deactivates
the excited state of 4a by radiationless decay pathway. Since ace-
tonitrile is a polar aprotic solvent it reduces the intramolecular
hydrogen bonding by interacting with the hydrogen in the sec-
ondary amine and hence the decrease in the extent of nonradiative
decay pathway, which results in biexponential behavior. In the case
of compound 5a monitoring the fluorescence lifetime decay at both
550 nm and 620 nm showed triexponential behavior and Table 4
presents the fluorescence lifetime of compound 5a in various
solvents.
0
10
20
30
40
50
Time (ns)
(c)
Fig. 3. Normalized absorptioneemission spectra of 4a (a), 5a (b) and fluorescence
lifetime of compounds 4a/5a (c).
To understand the dual emissive behavior of 5a, the fluores-
cence excitation spectra were recorded in acetonitrile. On moni-
toring at the shorter wavelength emission maximum (551 nm), two
distinct excitation bands were observed, one at 460 nm and the
other at 520 nm whereas for longer wavelength emission maxi-
mum (617 nm), it showed only one excitation band around 460 nm
(Fig. 4(b)). The existence of two excitation band indicates that the
origin of the dual emission behavior is from the two different
chromophore of the same molecule.
The excitation band observed at 520 nm corresponds to the
locally excited state and the one at 460 nm overlaps with the 1-
1.0
4a
5a_551 nm
1.0
4b
5a_617 nm
4c
4d
0.8
4e
4f
0.8
0.6
0.4
0.2
0.0
4g
4h
4i
0.6
0.4
0.2
0.0
The shorter component (w0.4e0.9 ns) is attributed to either the
intramolecular hydrogen bonding in nonpolar solvent/polar aprotic
solvents or the intermolecular hydrogen bonding with the polar
protic solvents. The longer component (w6e10 ns) is attributed to
the locally excited state, which found to have greater pre-
exponential factor, which indicates that the radiationless de-
activation pathway is hindered, i.e., the molecular structure is not
favoring the intramolecular hydrogen bonding.
300
350
400
450
500
550
600
350
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
(a)
(b)
Fig. 4. Excitation spectrum of (a) 4aei and (b) 5a.

S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
2895
Table 3
Table 4
Fluorescence lifetime decay of 4a in various solvents
Fluorescence lifetime data of 5a monitored at 550 nm (a) and 620 nm (b) in various
solvents
10000
1000
100
10
prompt
10000
Prompt
4a_Hexane
4a_Acetonitrile
4a_Methanol
5a_Hexane_551 nm
5a_Acetonitrile_551 nm
5a_Methanol_551 nm
1000
100
10
1
1
0
10
20
30
40
50
Time (ns)
0
10
20
30
40
50
Time (ns)
Solvent
Lifetime (ns)
Relative amplitude
(a)
s1
s2
A1
A2
10000
1000
100
10
Prompt
Hexane
CH3CN
MeOH
0.698
0.396
0.318
d
1
0.93
1
d
5a_Hexane_620 nm
5a_Acetonitrile_620 nm
5a_Methanol_620 nm
6.47
d
0.07
d
In compound 4a the spiro ring carbonyl decreases the electron
density around the secondary amine and hence it favors the
intramolecular hydrogen bonding by increasing the acidity of the
amino nitrogen. Whereas in case of 5a, the electron withdrawing
group is far away from the secondary amine and hence the intra-
molecular hydrogen bonding is not facilitated, which results in poor
radiationless deactivation pathway (Fig. 6). However in methanol
the intermolecular hydrogen bonding induces the radiationless
deactivation process, which is clearly evident from its fluorescence
decay profile. Introducing another hydrogen bonding donor group
(eNH2) may enhance the radiationless deactivation process and to
explore phenomena, compound 5I synthesized and showed no
emission because its excited state is completely deactivated by
nonradiative decay process. Another lifetime component
(w1.7e3 ns) may be attributed to the aminoanthraquinone fluo-
rophore, which is responsible for the dual emission in the steady
state emission spectrum. Though compounds 4a and 5a showed
very close absorption maxima (519 and 521 nm) in solution and 533
and 546 nm in solid state (Fig. 5(b)), they differ in their color, one is
pink and another is violet. Both in solution and solid state, com-
pound 4a showed only a strong absorption band whereas com-
pound 5a showed broad absorption band. The fluorescence
excitation spectrum revealed that compound 4a has got one ab-
sorption band at 520 nm whereas compound 5a has got two strong
absorption bands at 460 nm and 520 nm (Fig. 4). Hence, although
their absorption maxima for compounds 4a and 5a are almost the
same but their absorption behavior are different and hence the
difference in color has been seen.
1
0
10
20
30
40
50
Time (ns)
(b)
Solvent
Monitored at 550 nm
Lifetime (ns)
Relative amplitude
s1
s2
s3
A1
A2
A3
Hexane
CH3CN
MeOH
0.945
0.751
0.467
2.3
2.42
2.16
7.58
9.59
6.2
0.20
0.15
0.11
0.47
0.38
0.24
0.33
0.47
0.66
Solvent
Monitored at 620 nm
Lifetime (ns)
Relative amplitude
s1
s2
s3
A1
A2
A3
Hexane
CH3CN
MeOH
0.701
0.494
0.407
1.73
1.92
3.04
6.68
10.57
7.39
0.39
0.14
0.51
0.33
0.15
0.19
0.28
0.71
0.30
O
O
O
N
O
H
N
H
Absorption and emission data, Stokes shift, fluorescence quan-
tum yield, and fluorescence lifetimes of all the compounds (4aei
and 5ael) have been determined (Table 5). Solvatochromism of 4a
and 5a have been explored for absorption and fluorescence studies
(See Supplementary data). Compliments to the new compounds
and possible application as fluorophores absorbing at longer
wavelength with emission at red or near infrared could exhibit
advantages, such as low scattering, deep penetration, minimal in-
terfering absorption, and fluorescence from biological systems.24
O
O
N
N
4a
5a
Fig. 6. Possible intramolecular hydrogen bonding in compounds 4a and 5a.
reaction of isatins, aryl alkynes, and 1-aminoanthraquinone. The
unusual reactivity of 1-aminoanthraquinone provided structurally
unique oxindoles as possible fluorophores. Remarkably, this new
class of compounds has large Stokes shifts and pronounced fluo-
rescence in orange-red region. Based on experimental observation,
a plausible reaction mechanism has been proposed. The final
compounds have also been found core structure of many drug
molecules.
3. Conclusion
We have developed a novel and efficient copper catalyzed
synthesis of a number of highly conjugated regioisomers of 3-
spiroheterocyclic 2-oxindoles 4aei and 5ael via multicomponent

2896
S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
Table 5
Selected absorption and emission data, Stokes shifts, fluorescence quantum yields and fluorescence lifetimes of 4aei and 5ael (recorded in acetonitrile, T¼298 K)
b
c
Compound
Absorptiona lmax, [nm] (log ε)
Emission lmax, [nm]
Quantum yield (ff
)
Stokes shift
D
ῡ (cmꢁ1
)
Fluorescence lifetimesd s1 [ns]
4a
5a
4b
5b
4c
5c
4d
5d
4e
5e
4f
249 (4.59), 519 (3.93)
635
551, 617
622
589
634
551, 597
630
549, 603
622
635
630
549, 603
634
552, 602
589
551, 617
634
551, 597
634
d
0.020
0.006
0.023
0.005
0.013
0.002
0.014
0.002
0.016
0.003
0.019
0.002
0.015
0.002
0.014
0.005
0.015
0.004
0.005
d
3409
827
3454
2364
3569
719
3620
979
3570
1254
3507
866
0.396 (0.93), 6.47 (0.07)
0.751 (0.15), 2.42 (0.38), 9.59 (0.47)
0.511 (0.91) 3.68 (0.09)
0.631 (0.19) 2.86 (0.24) 6.61 (0.57)
0.428 (0.91) 3.20 (0.89)
252 (4.90), 332 (3.93), 521 (3.93)
249 (4.88), 330 (4.47), 514 (4.10)
252 (4.84), 334 (4.03) 517 (3.87)
248 (5.15), 517 (4.43)
252 (4.83), 336 (4.02), 528 (3.86)
253 (4.75), 511 (3.83)
252 (4.84), 338 (3.98), 521 (3.86)
251 (4.68), 513 (3.99)
251 (4.84), 331 (4.01), 518 (3.85)
257 (4.82), 518 (4.12)
252 (4.93), 336 (3.94), 527 (3.89)
249 (4.71), 523 (3.94)
252 (4.92), 333 (4.04), 534 (3.83)
248 (4.63), 516 (3.96)
251 (4.67), 334 (3.77), 517 (3.68)
255 (4.65), 514 (3.83)
253 (4.83), 336 (3.89), 534 (3.81)
253 (4.66), 513 (3.73)
0.876 (0.25) 2.35 (0.41) 8.40 (0.34)
0.407 (0.81) 1.58 (0.08) 6.60 (0.11)
0.375 (0.26) 2.01 (0.39) 6.33 (0.35)
0.050 (0.22) 0.45 (0.73) 3.56 (0.05)
0.496 (0.25) 1.79 (0.30) 5.84 (0.45)
0.378 (0.68) 0.63 (0.22) 4.42 (0.10)
0.545 (0.28) 2.08 (0.35) 6.73 (0.37)
0.341 (0.78) 1.50 (0.10) 8.87 (0.12)
0.578 (0.12) 2.28 (0.57) 6.84 (0.31)
0.044 (0.21) 0.39 (0.73) 1.49 (0.06)
0.491 (0.23) 1.33 (0.18) 8.37 (0.59)
0.330 (0.58) 1.22 (0.32) 6.80 (0.10)
0.475 (0.27) 1.81 (0.46) 6.04 (0.27)
0.843 (0.27) 1.77 (0.30) 7.69 (0.43)
d
5f
4g
5g
4h
5h
4i
5i
5j
5l
3348
611
3645
3082
3545
3070
3390
d
251 (4.37), 606 (3.53)
a
Recorded for the concentration of 10ꢁ5 mol/L.
Rhodamine 6G in ethanol as standard.
b
c
Stoke shift¼lmax,abs
ꢁ
lmax,emi [cmꢁ1].
d
Determined by time correlated single photon counting at an excitation wavelength of 375 nm and monitored at their respective emission maximum.
4. Experimental section
(s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d 26.9, 53.9, 97.4, 108.5,
120.2, 123.9, 125.4, 125.6, 127.0, 127.1, 128.4, 129.0, 129.1, 129.2,
132.9, 133.7, 133.8, 134.3, 134.4, 134.5, 135.3, 138.1, 138.4, 142.3,
142.4, 178.6, 182.9, 186.4; HRMS (ESI-TOF) m/z: [M]þ calcd for
C31H20N2O3 468.1474; found 468.1491.
4.1. Typical experimental procedure
A mixture of N-methylisatin 1a (161 mg, 1 mmol, 1 equiv), phe-
nylacetylene 2a (0.12 mL, 1 mmol, 1.2 equiv), 1-aminoanthraquinone
(0.266 g, 1 mmol, 1.2 equiv) 3a, cuprous chloride (9.9 mg, 10 mol %),
and copper(II) triflate (36.1 mg, 10 mol %) in dry toluene (4 mL) was
refluxed at 120 ꢀC for 24 h under nitrogen atmosphere. The progress
of the reaction was monitored by TLC. After completion of the re-
action, the mixture was cooled to room temperature, filtered
through a pad of neutral alumina using ethyl acetate as a solvent. The
solvent was evaporated in vacuo and the residue was chromato-
graphed on neutral alumina using gradient elution of hexane/ethyl
acetate as solvent to yield compounds 4a as pink powder, 183 mg,
39% yield and 5a as violet powder, 197 mg, 42% yield.
4.1.3. (R)-1-Methyl-5-nitro-40-phenyl-10H-spiro[indoline-3,20-naph-
tho[2,3-h]quinoline]-2,70,120-trione (4b). Pink powder, 216 mg, 42%
yield; Rf (30% EtOAc/Hexane) 0.47; IR (KBr) lmax: 3448, 2925, 1740,
1662, 1612, 1489, 1336, 1274, 1052, 723 cmꢁ1; 1H NMR (CDCl3/TMS,
500.1 MHz):
d
3.31 (s, 3H), 5.39 (d, J¼2.3 Hz, 1H), 6.99 (d, J¼8.4 Hz,
1H), 7.32e7.36 (m, 3H), 7.40e7.43 (m, 3H), 7.60 (d, J¼7.65 Hz, 1H),
7.74 (t, J¼3.8 Hz, 2H), 8.15e8.17 (m,1H), 8.25e8.26 (m,1H), 8.35 (dd,
J¼8.4, 2.25 Hz, 1H), 8.45 (d, J¼2.3 Hz, 1H), 10.40 (s, 1H); 13C NMR
(CDCl3/TMS, 125.7 MHz): d 27.2, 63.8, 108.6, 113.3, 117.8, 121.2, 121.6,
125.6,126.8,127.1,127.4,128.7,128.8,128.9,132.0,133.3,133.7,133.9,
134.1,134.6,137.0,140.1,144.4,147.1,147.8,175.4,182.8,185.7; HRMS
(ESI-TOF) m/z: [M]þ calcd for C31H19N3O5 513.1325; found 513.1325.
4.1.1. (R)-1-Methyl-40-phenyl-10H-spiro[indoline-3,20-naphtho[2,3-h]
quinoline]-2,70,120-trione (4a). Pink crystals: mp 210 ꢀC; 183 mg,
39% yield; Rf (30% EtOAc/Hexane) 0.51; IR (KBr) lmax: 3438, 2927,
4.1.4. (R)-1-Methyl-5-nitro-20-phenyl-10H-spiro[indoline-3,40-naph-
tho[2,3-h]quinoline]-2,70,120-trione (5b). Violet powder, 232 mg,
45% yield; Rf (30% EtOAc/Hexane) 0.46; IR (KBr) lmax: 3437, 2925,
1725, 1657, 1622, 1485, 1341, 1274, 1131, 1021, 722 cmꢁ1 1H NMR
;
(CDCl3/TMS, 500.1 MHz):
d
3.24 (s, 3H), 5.44 (d, J¼2.3 Hz, 1H), 6.89
(d, J¼7.65 Hz, 1H), 7.14 (t, J¼7.65 Hz, 1H), 7.29 (d, J¼8.4 Hz, 1H),
7.34e7.42 (m, 6H), 7.53e7.57 (m, 2H), 7.70e7.75 (m, 2H), 8.18 (d,
J¼7.65 Hz, 1H), 8.25 (d, J¼7.65 Hz, 1H), 10.35 (s, 1H); 13C NMR
1731, 1664, 1605, 1495, 1334, 1271, 1058, 995, 748 cmꢁ1
;
1H NMR
(CDCl3/TMS, 500.1 MHz):
d 3.39 (s, 3H), 4.82 (s, 1H), 6.87 (d,
J¼7.65 Hz, 1H), 7.05 (d, J¼8.4 Hz, 1H), 7.44e7.50 (m, 3H), 7.69 (d,
J¼6.85 Hz, 2H), 7.72 (d, J¼7.6 Hz, 1H), 7.77e7.84 (m, 2H), 8.14 (d,
J¼1.55 Hz, 1H), 8.26 (d, J¼7.65 Hz, 1H), 8.32e8.36 (m, 2H), 11.72 (s,
(CDCl3/TMS, 125.7 MHz):
d 26.8, 64.2, 108.8, 112.9, 117.4, 123.4,
123.9, 125.5, 126.4, 126.7, 126.9, 128.4, 128.7, 129.0, 130.4, 131.5,
133.2, 133.3, 133.9, 133.9, 134.9, 137.6, 139.0, 142.24, 147.9, 175.2,
182.9, 185.3; HRMS (ESI-TOF) m/z: [M]þ calcd for C31H20N2O3
468.1474; found 468.1482.
1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d 27.3, 53.8, 95.3, 108.2,
120.3, 121.6, 125.5, 126.2, 126.4, 127.1, 127.2,129.1,129.6, 132.9, 134.1,
134.4, 134.5, 134.9, 138.6, 139.5, 141.9, 144.4, 147.9, 165.9, 178.7,
182.7, 186.5; HRMS (ESI-TOF) m/z: [M]þ calcd for C31H19N3O5
513.1325; found 513.1338.
4.1.2. (R)-1-Methyl-20-phenyl-10H-spiro[indoline-3,40-naphtho[2,3-
h]quinoline]-2,70,120-trione (5a). Violet crystals: 295 ꢀC; 197 mg,
42% yield; Rf (30% EtOAc/Hexane) 0.50; IR (KBr) lmax: 3438, 3064,
4.1.5. (R)-1,5-Dimethyl-40-phenyl-10H-spiro[indoline-3,20-naphtho
[2,3-h]quinoline]-2,70,120-trione (4c). Pink powder, 184 mg, 38%
yield; Rf (30% EtOAc/Hexane) 0.54; IR (KBr) lmax: 3441, 2925, 1724,
1660, 1627, 1492, 1347, 1274, 1099, 1020, 721 cmꢁ1; 1H NMR (CDCl3/
2928, 1717, 1662, 1590, 1495, 1333, 1271, 1088, 995, 748 cmꢁ1
;
1H
NMR (CDCl3/TMS, 500.1 MHz):
d 3.31 (s, 3H), 4.90 (s, 1H), 6.91 (d,
J¼7.65 Hz, 1H), 6.95 (d, J¼7.65 Hz, 1H), 7.09 (t, J¼7.65 Hz, 1H), 7.25
(d, J¼4.6 Hz, 1H), 7.35 (t, 8.4 Hz, 1H), 7.41 (d, J¼6.85 Hz, 1H), 7.46 (t,
J¼7.65 Hz, 2H) 7.69 (d, J¼7.65 Hz, 3H), 7.76 (t, J¼7.65 Hz, 1H), 7.81 (t,
J¼7.65 Hz, 1H), 8.25 (d, J¼7.65 Hz, 1H), 8.34 (d, J¼7.65 Hz, 1H), 11.67
TMS, 500.1 MHz):
d 2.33 (s, 3H), 3.22 (s, 3H), 5.44 (s, 1H), 6.78 (d,
J¼8.05 Hz, 1H), 7.17 (d, J¼8.0 Hz, 1H), 7.29 (d, J¼8.05 Hz, 1H),
7.35e7.42 (m, 6H), 7.56 (d, J¼8.0 Hz, 1H), 7.70e7.75 (m, 2H), 8.18 (d,

S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
2897
J¼6.9 Hz, 1H), 8.25 (d, J¼7.41 Hz, 1H), 10.35 (s, 1H); 13C NMR (CDCl3/
TMS, 125.7 MHz): 21.1, 26.8, 64.3, 108.6, 112.8, 117.4, 123.7, 126.3,
126.4, 126.7, 126.9, 128.4, 128.7, 129.0, 130.7, 131.4, 133.2, 133.3,
133.7, 133.8, 134.0, 134.9, 137.6, 138.8, 139.8, 147.9, 175.2, 182.9,
185.3; HRMS (ESI-TOF) m/z: [M]þ calcd for C32H22N2O3 482.1630;
found 482.1645.
1H), 7.43 (d, J¼7.65 Hz, 1H), 7.47 (t, J¼7.65 Hz, 2H), 7.70 (t,
J¼7.68.45 Hz, 3H), 7.74e7.81 (m, 2H), 8.24 (d, J¼7.65 Hz, 1H), 8.32
(d, J¼7.65 Hz, 1H), 11.68 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d
27.0, 54.2, 96.3, 109.0, 119.6, 120.3, 122.3, 125.5, 127.1, 127.2, 127.3,
128.4, 129.1,129.4,132.9,133.9,134.3,134.4,135.1,138.9,139.2,141.1,
142.1, 145.7, 178.4, 182.8, 186.5; HRMS (ESI-TOF) m/z: [MþNa]þ
calcd for C32H19F3N2O4Na 575.1194; found 575.1182.
4.1.6. (R)-1,5-Dimethyl-20-phenyl-10H-spiro[indoline-3,40-naphtho
[2,3-h]quinoline]-2,70,120-trione (5c). Violet powder, 193 mg, 40%
yield; Rf (30% EtOAc/Hexane) 0.53; IR (KBr) lmax: 3430, 3065, 2925,
1715,1666,1629,1589,1496,1466,1270,1094, 994, 807, 736 cmꢁ1; 1H
4.1.11. (R)-5-Bromo-1-methyl-40-phenyl-10H-spiro[indoline-3,20-
naphtho[2,3-h]quinoline]-2,70,120-trione (4f). Pink powder 209 mg,
38% yield; Rf (30% EtOAc/Hexane) 0.55; IR (KBr) lmax: 3441, 3064,
NMR (CDCl3/TMS, 500.1 MHz):
d
2.27 (s, 3H), 3.29 (s, 3H), 4.91 (d,
2926, 1729, 1658, 1482, 1274, 1099, 1021, 810, 718 cmꢁ1
;
1H NMR
J¼2.3 Hz,1H), 6.82 (d, J¼8.4 Hz,1H), 6.91 (d, J¼7.6 Hz,1H), 7.07 (s,1H),
7.13 (d, J¼7.65 Hz, 1H), 7.38e7.46 (m, 3H), 7.67e7.79 (m, 5H), 8.22 (d,
J¼7.65 Hz, 1H), 8.31 (d, J¼7.65 Hz,1H),11.66 (m,1H). 13C NMR (CDCl3/
TMS,125.7 MHz): 21.2, 26.9, 54.0, 97.7,108.2,114.7,120.2,125.4,126.3,
126.9, 127.1, 128.7, 129.0, 129.2, 129.4, 132.9, 133.6, 133.7, 133.8, 134.3,
134.5,135.30,138.2,138.3,139.9,142.3,178.6,182.9,186.4; HRMS (ESI-
TOF) m/z: [M]þ calcd for C32H22N2O3 482.1630; found 482.1643.
(CDCl3/TMS, 500.1 MHz): d 3.23 (s, 3H), 5.41 (s, 1H), 6.78 (d,
J¼8.4 Hz, 1H), 7.31 (d, J¼7.65 Hz, 1H), 7.35 (d, J¼7.65 Hz, 2H),
7.40e7.45 (m, 3H), 7.51 (d, J¼8.4 Hz, 1H), 7.58 (d, J¼7.65 Hz, 1H),
7.66 (s, 1H), 7.72e7.77 (m, 2H), 8.19 (d, J¼9.15 Hz, 1H), 8.25 (d,
J¼6.85 Hz, 1H), 10.36 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d
26.9, 64.2, 110.4, 113.0, 116.5, 117.5, 122.4, 126.0, 126.8, 127.0, 128.5,
128.7,128.8,128.9,131.7,133.3,133.5,133.9,134.1,134.8,134.9,137.3,
139.4, 141.3, 147.5, 165.9, 174.7, 182.8, 185.5; HRMS (ESI-TOF) m/z:
[MþNa]þ calcd for C31H19BrN2O3Na 571.0456; found 571.0806.
4.1.7. (R)-5-Iodo-1-methyl-40-phenyl-10H-spiro[indoline-3,20-naph-
tho[2,3-h]quinoline]-2,70,120-trione (4d). Pink powder 238 mg, 40%
yield; Rf (30% EtOAc/Hexane) 0.56; IR (KBr) lmax: 3432, 2925, 1727,
1659, 1630, 1598, 1484, 1334, 1273, 1098, 721 cmꢁ1; 1H NMR (CDCl3/
4.1.12. (R)-5-Bromo-1-methyl-20-phenyl-10H-spiro[indoline-3,40-
naphtho[2,3-h]quinoline]-2,70,120-trione (5f). Violet powder 247 mg,
45% yield; Rf (30% EtOAc/Hexane) 0.54; IR (KBr) lmax: 3435, 3066,
TMS, 500.1 MHz):
d
3.22 (s, 3H), 5.40 (s, 1H), 6.68 (d, J¼8.05 Hz, 1H),
7.30 (d, J¼7.45 Hz, 1H), 7.35 (d, J¼7.45 Hz, 2H), 7.39e7.42 (m, 3H),
7.58 (d, J¼8 Hz,1H), 7.69e7.75 (m, 3H), 7.81 (s,1H), 8.19 (d, J¼6.85 Hz,
1H), 8.25 (d, J¼6.9 Hz, 1 H), 10.35 (s, 1H). 13C NMR (CDCl3/TMS,
2927, 1721, 1663, 1591, 1487, 1328, 1269, 1095, 995, 750, 718 cmꢁ1
;
1H NMR (CDCl3/TMS, 500.1 MHz):
d 3.29 (s, 3H), 4.86 (s,1H), 6.83 (d,
J¼8.4 Hz, 1H), 6.90 (d, J¼7.65 Hz, 1H), 7.37 (d, J¼1.5 Hz, 1H), 7.42 (d,
J¼6.9 Hz, 1H), 7.45e7.48 (m, 3H), 7.70 (t, J¼9.15 Hz, 3H), 7.74e7.81
(m, 2H), 8.24 (d, J¼7.65 Hz, 1H), 8.32 (d, J¼6.9 Hz, 1H), 11.67 (s, 1H);
125.7 MHz):
d 26.8, 64.0, 86.3, 110.9, 113.0, 117.6, 122.5, 126.0, 126.8,
127.0, 128.5, 128.7, 128.9, 131.7, 133.3, 133.5, 133.9, 134.1, 134.3, 134.8,
135.2, 137.3, 139.3, 139.4, 141.9, 147.5, 174.5, 182.9, 185.5. HRMS (ESI-
TOF) m/z: [M]þ calcd for C31H19IN2O3 594.0440; found 594.0457.
13C NMR (CDCl3/TMS, 125.7 MHz):
d 26.9, 54.0, 96.5, 110.0, 114.9,
116.4,120.3,125.4,127.1,127.2,127.5,128.8,129.1,129.4,132.0, 132.9,
133.9, 134.3, 134.4, 134.4, 135.1, 138.8, 139.8, 141.4, 142.1, 178.1, 182.8,
186.5; HRMS (ESI-TOF) m/z: [MþNa]þ calcd for C31H19BrN2O3Na
571.0456; found 571.0806.
4.1.8. (R)-5-Iodo-1-methyl-20-phenyl-10H-spiro[indoline-3,40-naph-
tho[2,3-h]quinoline]-2,70,120-trione (5d). Violet powder 250 mg, 42%
yield; Rf (30% EtOAc/Hexane) 0.55; IR (KBr) lmax: 3427, 2927, 1719,
1631, 1663, 1590, 1487, 1329, 1269, 1093, 994, 748, 719 cmꢁ1
;
1H
4.1.13. (R)-1-Methyl-40-p-tolyl-10H-spiro[indoline-3,20-naphtho[2,3-
h]quinoline]-2,70,120-trione (4g). Pink powder 169 mg, 35% yield; Rf
(30% EtOAc/Hexane) 0.55; IR (KBr) lmax: 3437, 2926,1725, 1661, 1613,
NMR (CDCl3/TMS, 500.1 MHz):
d 3.28 (s, 3H), 4.85 (s, 1H), 6.72 (d,
J¼8.4 Hz, 1H), 6.89 (d, J¼8.4 Hz, 1H), 7.41e7.48 (m, 3H), 7.52 (d,
J¼1.5 Hz, 1H), 7.65 (d, J¼8.4 Hz, 1H), 7.69 (t, J¼7.65 Hz, 3H),
7.73e7.80 (m, 2H), 8.23 (d, J¼7.65 Hz, 1H), 8.31 (d, J¼7.6 Hz, 1H),
1486, 1369, 1341, 1274, 1018, 753, 722 cmꢁ1 1H NMR (CDCl3/TMS,
;
500.1 MHz):
d
2.38 (s, 3H), 3.24 (s, 3H), 5.43 (s, 1H), 6.89 (d, J¼8.4 Hz,
11.66 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d
26.9, 53.8, 86.3,
1H), 7.13 (t, J¼7.65 Hz, 1H), 7.20e7.23 (m, 3H), 7.32 (d, J¼7.65 Hz, 1H)
7.37 (t, J¼6.9 Hz,1H), 7.54 (t, J¼8.4 Hz, 2H), 7.67e7.73 (m, 3H), 8.16 (d,
J¼6.9 Hz, 1H), 8.23 (d, J¼7.65 Hz, 1H), 10.35 (s, 1H). 13C NMR (CDCl3/
96.5, 110.6, 114.9, 120.3, 125.4, 127.1, 127.1, 127.5, 132.9, 133.9, 134.3,
135.1, 137.9, 138.7, 140.2, 142.1, 177.9, 182.8, 186.4; HRMS (ESI-TOF)
m/z: [M]þ calcd for C31H19IN2O3 594.0440; found 594.0452.
TMS, 125.7 MHz):
d 21.4, 26.8, 64.2, 108.8, 112.9, 117.4, 123.1, 123.9,
125.5, 126.6, 126.7, 126.9, 128.9, 129.3, 130.4, 131.5, 133.2, 133.3, 134.0,
134.6, 134.9, 138.2, 138.9, 142.2, 147.9, 175.3, 182.9, 185.3; HRMS (ESI-
TOF) m/z: [M]þ calcd for C32H22N2O3 482.1630; found 482.1621.
4.1.9. (R)-1-Methyl-40-phenyl-5-(trifluoromethoxy)-10H-spiro[indo-
line-3,20-naphtho[2,3-h]quinoline]-2,70,120-trione (4e). Pink powder
216 mg, 39% yield; Rf (30% EtOAc/Hexane) 0.47; IR (KBr) lmax: 3438,
2928, 1732, 1660, 1628, 1490, 1264, 1165, 720 cm1; 1H NMR (CDCl3/
4.1.14. (R)-1-Methyl-20-p-tolyl-10H-spiro[indoline-3,40-naphtho[2,3-h]
quinoline]-2,70,120-trione (5g). Violet powder 188 mg, 39% yield; Rf
(30% EtOAc/Hexane) 0.54; IR (KBr) lmax: 3443, 2925, 1718, 1668,
TMS, 500.1 MHz):
d
3.25 (s, 3H), 5.42 (s, 1H), 6.89 (d, J¼8.4 Hz, 1H),
7.26e7.28 (m, 1H), 7.31 (d, J¼8.4 Hz, 1H), 7.35 (d, J¼8.4 Hz, 2H),
7.39e7.44 (m, 3H), 7.45 (s, 1H), 7.58 (d, J¼8.4 Hz, 1H), 7.71e7.77 (m,
2H), 8.18 (d, J¼6.85 Hz, 1H), 8.25 (d, J¼6.9 Hz, 1H), 10.36 (s, 1H). 13C
1589, 1497, 1466, 1336, 1270, 1088, 750, 718 cmꢁ1 1H NMR (CDCl3/
;
TMS, 500.1 MHz):
d 2.39 (s, 3H), 3.31 (s, 3H), 4.86 (s, 1H), 6.90 (d,
NMR (CDCl3/TMS, 125.7 MHz):
d
26.9, 64.3, 109.4, 113.1, 117.6, 119.5,
J¼8.4 Hz,1H), 6.95 (d, J¼8.4 Hz,1H), 7.09 (t, J¼7.65 Hz,1H), 7.26e7.27
(m, 2H), 7.35 (t, J¼7.65 Hz, 1H), 7.58 (d, J¼7.63 Hz, 2H), 7.68 (d,
J¼7.65 Hz, 1H), 7.74e7.80 (m, 3H), 8.25 (d, J¼7.65 Hz, 1H), 8.34 (d,
J¼7.65 Hz, 1H), 11.64 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
122.3, 123.6, 126.0, 126.8, 127.0, 128.5, 128.7, 128.9, 131.7, 133.3,
133.5, 133.9, 134.1, 134.5, 134.7, 137.3, 139.6, 140.9, 145.7, 147.5, 175.1,
182.9, 185.5; HRMS (ESI-TOF) m/z: [MþNa]þ calcd for
C32H19F3N2O4Na 575.1194; found 575.1195.
d
21.4, 26.9, 53.9, 96.7, 108.4, 120.1, 123.9, 125.3, 125.6, 127.0, 127.1,
128.5, 129.1, 129.7, 132.4, 132.9, 133.7, 133.8, 134.3, 134.4, 134.5, 138.2,
138.3, 139.2, 142.4, 178.7, 182.9, 186.4 HRMS (ESI-TOF) m/z: [M]þ
calcd for C32H22N2O3 482.1630; found 482.1647.
4.1.10. (R)-1-Methyl-20-phenyl-5-(trifluoromethoxy)-10H-spiro[indo-
line-3,40-naphtho[2,3-h]quinoline]-2,70,120-trione (5e). Violet pow-
der 254 mg, 46% yield; Rf (30% EtOAc/Hexane) 0.46; IR (KBr) lmax
3444, 1724, 1667, 1630, 1587, 1495, 1467, 1264, 1166, 1096, 717 cm1;
1H NMR (CDCl3/TMS, 500.1 MHz):
3.31 (s, 3H), 4.86 (s, 1H), 6.89 (d,
J¼7.65 Hz, 1H), 6.94 (d, J¼8.4 Hz, 1H), 7.17 (s, 1H), 7.23 (d, J¼8.45 Hz,
:
4.1.15. (R)-40-(4-Fluorophenyl)-1-methyl-10H-spiro[indoline-3,20-
naphtho[2,3-h]quinoline]-2,70,120-trione (4h). Pink powder 161 mg,
33% yield; Rf (30% EtOAc/Hexane) 0.53; IR (KBr) lmax: 3438, 2929,
d

2898
S. Periyaraja et al. / Tetrahedron 69 (2013) 2891e2899
1725, 1659, 1612, 1486, 1341, 1275, 1154, 1092, 844, 724 cmꢁ1
;
1H
3.25 (s, 3H), 5.43 (d, J¼1.5 Hz, 1H),
11.72 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d 26.8, 53.9, 98.9,
NMR (CDCl3/TMS, 500.1 MHz):
d
108.6, 114.9, 120.5, 123.9, 125.6, 125.8, 126.0, 126.1, 127.1, 127.1, 128.1,
129.3, 132.9, 133.8, 134.0, 134.4, 134.5, 137.4, 137.8, 138.7, 142.0,
142.4, 178.3, 182.8, 186.6; HRMS (ESI-TOF) m/z: [MþNa]þ calcd for
C32H19F3N2O3Na 559.1245; found 559.1232.
6.90 (d, J¼7.65 Hz, 1H), 7.10 (t, J¼8.4 Hz, 2H), 7.15 (t, J¼7.65 Hz, 1H),
7.25 (d, J¼7.65 Hz, 1H), 7.33 (dd, J¼5.35, 3.1 Hz, 2H), 7.39 (t,
J¼7.65 Hz, 1H), 7.54 (d, J¼6.85 Hz, 1H), 7.57 (d, J¼7.6 Hz, 1H),
7.70e7.75 (m, 2H), 8.17 (d, J¼6.85 Hz, 1H), 8.25 (d, J¼7.6 Hz, 1H),
10.34 (s, 1H). 13C NMR (CDCl3/TMS, 125.7 MHz):
d
26.8, 64.15, 108.9,
4.1.20. (R)-60-Amino-1-methyl-20-phenyl-10H-spiro[indoline-3,40-
naphtho[2,3-h]quinoline]-2,70,120-trione (5l). Violet powder 223 mg,
46% yield; Rf (30% EtOAc/Hexane) 0.43; IR (KBr) lmax: 3423, 3303,
3060, 2926, 2857, 1709, 1605, 1523, 1483, 1346, 1267, 1086, 1022, 748,
112.9,115.6,115.8,117.4,123.6,123.9,125.5,126.2,126.7,127.0,130.5,
130.7,130.8, 131.3,133.0,133.3,133.4,133.5,133.9, 134.1,134.8, 138.1,
142.22, 147.8, 164.8 (d, J¼272.16 Hz, CeF coupling), 175.2, 182.9,
185.3; HRMS (ESI-TOF) m/z: [MþNa]þ calcd for C31H19FN2O3Na
509.1277; found 509.1245.
699 cmꢁ1; 1H NMR (CDCl3/TMS, 500.1 MHz):
d 3.33 (s, 3H), 4.91 (s,
1H), 6.32 (s,1H), 6.94 (d, J¼7.5 Hz,1H), 7.06 (t, J¼7.5 Hz,1H), 7.11e7.15
(m, 2H), 7.22 (d, J¼8.5 Hz, 1H), 7.32 (t, J¼7.5 Hz, 1H), 7.40 (t, J¼7.5 Hz,
1H), 7.46 (t, J¼7.5 Hz, 2H), 7.60 (t, J¼7.5 Hz, 1H), 7.67 (t, J¼7.5 Hz, 1H),
7.74 (d, J¼7.5 Hz, 2H), 8.15 (d, J¼7.5 Hz, 1H), 8.23 (d, J¼7.5 Hz, 1H),
4.1.16. (R)-20-(4-Fluorophenyl)-1-methyl-10H-spiro[indoline-3,40-
naphtho[2,3-h]quinoline]-2,70,120-trione
(5h). Violet
powder
195 mg, 40% yield; Rf (30% EtOAc/Hexane) 0.52; IR (KBr) lmax: 3435,
12.36 (s, 1H); 13C NMR (CDCl3/TMS, 125.7 MHz):
d 26.9, 53.9, 96.5,
3067, 2928, 1715, 1663, 1598, 1496, 1332, 1272, 1161, 1091, 997, 841,
108.6, 110.8, 112.3, 124.0, 125.3, 125.4, 125.6, 126.4, 127.1, 127.9, 128.1,
128.3, 128.6, 129.0, 129.1, 132.5, 132.6, 132.8, 133.1, 133.9, 134.0, 135.5,
136.3, 137.5, 138.8, 142.0, 146.9, 178.9, 178.5, 183.3, 185.1; HRMS (ESI-
TOF) m/z: [M]þ calcd for C31H21N3O3Na 506.1480; found 506.1382.
748 cmꢁ1; 1H NMR (CDCl3/TMS, 500.1 MHz):
d 3.31 (s, 3H), 4.83 (s,
1H), 6.90 (d, J¼8.4 Hz, 1H), 6.95 (d, J¼7.65 Hz, 1H), 7.10 (t, J¼7.65 Hz,
1H), 7.14 (t, J¼8.4 Hz, 2H), 7.26 (d, J¼7.65 Hz, 1H), 7.36 (t, J¼7.65 Hz,
1H), 7.65e7.69 (m, 3H), 7.73e7.80 (m, 2H), 8.23 (d, J¼7.6 Hz, 1H),
8.30 (d, J¼7.65 Hz, 1H), 11.61 (s, 1H). 13C NMR (CDCl3/TMS,
Acknowledgements
125.7 MHz): d 26.9, 53.9, 97.3, 108.5, 114.8, 115.9, 116.1, 120.3, 123.9,
125.6, 127.1, 127.1, 127.3, 127.3, 128.3, 129.2, 131.5, 132.9, 133.7, 133.9,
134.3, 134.4, 134.6, 137.6, 138.0, 142.2, 142.4, 163.3 (d, J¼248.19 Hz,
CeF coupling), 178.6, 182.9, 186.5; HRMS (ESI-TOF) m/z: [MþNa]þ
calcd for C31H19FN2O3Na 509.1277; found 509.1268.
S.P. thanks CSIR (New Delhi) for the award of Senior Research
Fellowship. Thanks are due to Dr. P. Jaisankar CSIR-IICB, Kolkata for
providing HRMS data.
Supplementary data
4.1.17. (R)-40-(4-Methoxyphenyl)-1-methyl-10H-spiro[indoline-3,20-
naphtho[2,3-h]quinoline]-2,70,120-trione (4i). Pink powder 170 mg,
34% yield; Rf (30% EtOAc/Hexane) 0.51; IR (KBr) lmax: 3434, 3066,
Copies of 1H NMR, 13C NMR, UVevis, Emission, Excitation
spectra, Solvatochromism, Fluorescence lifetime, FTIR and HRMS
for all compounds has been provided. Supplementary data related
to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.02.037.
2932, 1722, 1660, 1611, 1484, 1275, 1022, 837, 722 cmꢁ1
;
1H NMR
(CDCl3/TMS, 500.1 MHz):
d 3.24 (s, 3H), 3.83 (s, 3H), 5.42 (d,
J¼1.5 Hz, 1H), 6.89 (d, J¼8.4 Hz, 1H), 6.93 (d, J¼8.4 Hz, 2H), 7.14 (t,
J¼7.6 Hz, 1H), 7.27 (d, J¼9.15 Hz, 2H), 7.33 (d, J¼7.65 Hz, 1H), 7.38 (t,
J¼7.65 Hz, 1H), 7.53 (d, J¼7.65 Hz, 1H), 7.56 (d, J¼7.65 Hz, 1H),
7.69e7.74 (m, 2H), 8.17 (d, J¼6.9 Hz, 1H), 8.24 (d, J¼6.85 Hz, 1H),
References and notes
10.34 (s, 1H). 13C NMR (CDCl3/TMS, 125.7 MHz):
d 26.8, 55.4, 64.2,
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108.8, 112.9, 114.0, 117.4, 123.0, 123.9, 125.5, 126.7, 126.9, 129.8,
130.2, 130.4, 131.4, 133.2, 133.3, 133.7, 134.0, 134.9, 138.6, 142.2,
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6.90 (d, J¼7.65 Hz, 1H), 6.95 (d, J¼8.4 Hz, 1H), 6.98 (d, J¼7.6 Hz, 2H),
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