Synthesis of biologically important, fluorescence active 5-hydroxy benzo[g]indoles through four-component domino condensations and their fluorescence "Turn-off" sensing of Fe(iii) ions

Article abstract of DOI:10.1039/c5ra05780a

Several highly substituted 2-pyrrolyl-2-cyanoacetamides were prepared through four-component domino condensation of various easily available 1,3-dicarbonyl compounds, amines, arylglyoxals and malononitrile. Subsequently these cyanoacetamide derivatives were converted into biologically important 5-hydroxy benzo[g]indoles through thermal cyclization under metal-free conditions. The synthesized 5-hydroxy benzo[g]indoles are fluorescence active with good quantum yields (Φ_F = ～0.50). They also show excellent fluorescence "Turn-off" sensing of Fe³⁺ ions (detection limit = ～1.2 × 10^-6 M). The interaction of 5-hydroxy benzo[g]indoles with Fe³⁺ ions can also be monitored through UV-Vis spectral change and naked-eye colour change in the presence and absence of UV radiation. The ¹H NMR titration unambiguously proves the formation of a complex between 5-hydroxy benzo[g]indoles and Fe³⁺ ion through the coordination of -OH groups with the metal. The binding constant of the complex (metal : ligand = 1 : 1) has been measured using Benesi-Hildebrand equation and found to be ～7.97 × 10³ M^-1.

Full text of DOI:10.1039/c5ra05780a

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Synthesis of biologically important, fluorescence active
5-hydroxy benzo[g]indoles through four-component domino
condensations and their fluorescence “Turn-off” sensing of
Fe(III) ions
Subhendu Maity, Ashis Kundu and Animesh Pramanik*
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkataꢀ700 009,
India
Eꢀmail:animesh_in2001@yahoo.co.in
ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
Abstract: Several highly substituted 2ꢀpyrrolylꢀ2ꢀcyanoacetamides were prepared through
fourꢀcomponent domino condensation of various easily available 1,3ꢀdicarbonyl compounds,
amines, arylglyoxals and malononitrile. Subsequently these cyanoacetamide derivatives were
converted to biologically important 5ꢀhydroxy benzo[g]indoles through thermal cyclization
under metal free condition. The synthesized 5ꢀhydroxy benzo[g]indoles are fluorescence active

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with good quantum yields (ΦF = ~ 0.50). They also show excellent fluorescence “Turnꢀoff”
sensing of Fe3+ ions (detection limit = ~1.2 x 10ꢀ6 M). The interaction of 5ꢀhydroxy
benzo[g]indoles with Fe3+ ions can also be monitored through UVꢀVis spectral change and
1
nakedꢀeye colour change in the presence and absence of UV radiation. The H NMR titration
unambiguously proves the formation of complex between 5ꢀhydroxy benzo[g]indoles and Fe3+
ion through the coordination of –OH group with the metal. The Binding Constant of the complex
(metal : ligand = 1:1) has been measured using BenesiꢀHildebrand equation and found to be
~7.97 x 103 Mꢀ1.
ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
Introduction
Nitrogen based heteocycles are important structural motifs for many natural products1
and pharmaceuticals2. They are also useful building blocks for various biologically active
molecules and functional materials.3 As for example carbazoles, the fused indole based
heterocycles, show important applications in materials science as organic lightꢀemitting materials
due to their wide band gap and high luminescent activity.4 Fused indole based polycyclic
frameworks with proper functionality can provide suitable ligand systems for diverse receptors.5
This type of ligands with fluorescence activity can act as sensing agent for different metal ion
through proper binding.6 Form biological point of view sensing of metal ions shows significant
demand in current research field.7 More specifically detection of iron level have significant
impact in biological research as iron regulates different biological processes such as electron
transfer reactions, binding and transport of oxygen, and cell growth and differentiation.8 To the
best of our knowledge suitable benzo[g]indole based molecules with fluorescence sensing
property have not been discovered as yet. So the development of new synthetic methodology for

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construction of benzo[g]indole scaffolds is important in organic synthesis. Although there are
number of methodologies for the synthesis of fused indole derivatives in literature9, synthesis of
substituted benzo[g]indoles are limited in number.10 Therefore, a simple, efficient, metalꢀfree,
regiocontrolled, and diversified synthesis of substituted benzo[g]indole derivatives is still highly
desirable. In continuation of our research interest in synthesis of various pyrrole and indole based
heterocycles,11 we wish to report herein an efficient synthetic strategy to access fluorescence
active 5ꢀhydroxy benzo[g]indoles from easily available starting materials. Since these
compounds possess phenolic –OH group as potential binding site the effect of various metal ions
on the fluorescence property has also been explored in solution phase. The selective ion sensitive
fluorescence changes lead to the finding of fluorescence “Turnꢀoff” sensor of Fe3+ ions.
Results and discussion
During our laboratory efforts on the development of multicomponent reactions for
synthesis of biologically important heterocyclic compounds, we discovered that refluxing a
mixture of acetylacetone 1 (R1 = Me), aniline 2 (R2 = Ph), phenyl glyoxal (3, R3 = H) and
malononitrile (4) in ethanol for 10 minutes produces a new compound 2ꢀ(4ꢀacetylꢀ5ꢀmethylꢀ1,2ꢀ
diphenylꢀ1Hꢀ3ꢀpyrrolyl)ꢀ2ꢀcyanoacetamide 5a in good yield, ~79% (Scheme 1). The reaction
proceeds through a fourꢀcomponent domino condensation among the reactants. Interestingly,
under the reaction conditions, one of the two cyano groups of malononitrile is selectively
hydrolyzed to an amide group. Subsequently we examine the viability of this reaction in other
solvents also such as acetonitrile, dioxane, DMF, THF and DCM for the formation of
cyanoacetamide 5a. However ethanol is found to be the best solvent in producing 5a in highest
yield (~79%) whereas acetonitrile produces 5a only in moderate yield (~40%). The other

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solvents including dioxane, DMF, THF and DCM produce very negligible amount of 5a. By
using the above methodology, a series of 2ꢀpyrrolylꢀ2ꢀcyanoacetamides 5aꢀz were synthesized in
ethanol medium by varying the 1,3ꢀdicarbonyl compounds, amines as well as the arylglyoxal
monohydrates (Scheme 1, Table 1). The results show that this fourꢀcomponent domino
condensation reaction provides an elegant and rapid way to access various 2ꢀpyrrolylꢀ2ꢀ
cyanoacetamides in a single synthetic operation from simple building blocks.
O
CN
O
H2N
R1
HO
O
O
R2
CN
Ethanol
+
+
O
+
NH2
OH
reflux
CN
R3
N
10 min
R1
4
2
3
R3
R2
1
5
R1 = Ph, Me, OEt
R2 = Aryl, Benzyl, Alkyl
R3 = H, Cl, OMe
(71ꢀ82%)
Scheme 1 Synthesis of 2ꢀpyrrolylꢀ2ꢀcyanoacetamides 5 through domino condensation.
Table 1 Synthesis of 2ꢀpyrrolylꢀ2ꢀcyanoacetamides 5 in ethanol.
Entry
1
R1
Me
R2
R3
H
Product
Yield(%)a
79
M. p.
160ꢀ162
5a
2
3
4
Me
Me
Me
H
H
H
76
73
74
168ꢀ170
146ꢀ148
180ꢀ182
5b
5c
5d
Br
Cl
F
5
Me
H
71
218ꢀ220
5e

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6
7
Me
Me
H
H
82
77
162ꢀ164
196ꢀ198
5f
O
5g
8
9
Me
Me
H
81
73
166ꢀ168
118ꢀ120
5h
5i
Cl
10
11
Me
Me
Cl
Cl
72
73
198ꢀ200
150ꢀ152
5j
5k
12
Me
Cl
79
184ꢀ186
5l
13
14
15
16
17
18
Me
Me
Me
Me
Me
Me
Cl
Cl
74
71
72
76
81
75
240ꢀ242
244ꢀ246
205ꢀ207
208ꢀ210
164ꢀ166
198ꢀ200
5m
5n
5o
5p
5q
5r
Br
Cl
F
Cl
Cl
O
OMe
OMe
Cl
19
20
Me
Me
OMe
OMe
78
81
88ꢀ90
5s
5t
152ꢀ154

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21
22
CO2Et
CO2Et
H
H
78
75
164ꢀ166
194ꢀ196
5u
5v
F
23
24
CO2Et
CO2Et
H
H
79
73
216ꢀ218
78ꢀ80
5w
5x
O
25
26
Ph
H
H
impureb
impureb
ꢀꢀ
ꢀꢀ
5y
5z
Ph
O
b
aIsolated Yield. Compounds 5y and 5z were not possible to isolate because of closely spaced
impurities. The crude masses were used for further reaction.
A proposed mechanism for the formation of compound 5 is shown in Scheme 2.12
Initially, a Knoevenagel condensation between arylglyoxal monohydrate 3 and malononitrile
produces α,βꢀunsaturated cyano intermediate 6. Then enamine 7, derived in situ from
acetylacetone 1 and amines 2, undergoes a Michaelꢀtype 1,4ꢀaddition with the intermediate 6 to
produce imminium intermediate 8, which subsequently tautomerizes to 9. Then the intermediate
9 most probably produces a fused furanoꢀpyrrole intermediate 10 through a tandem cyclization
process. Finally, the 2ꢀpyrrolylꢀ2ꢀcyanoacetamides 5 are formed through a rearrangement of
1
intermediate 10. All the compounds 5aꢀx were fully characterized by H and 13C NMR
spectroscopy, and the Xꢀray crystal structure analysis of 2ꢀ[4ꢀacetylꢀ2ꢀ(4ꢀchlorophenyl)ꢀ5ꢀ
methylꢀpꢀtolylꢀ1Hꢀ3ꢀpyrrolyl]ꢀ2ꢀcyanoacetamide (5j) further confirmed the structural assignment
(Fig. 1).13

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O
O
OH
OH
OH2
O
H
3
CN
CN
4
N
NH
NH
O
O
O
NC
O
NC
O
O
NC
H
6
H
N
NH
+
NH
8
9
7
O
H+
NC
NH2
O
O
NC
O
+
O
NH2
NH2
H
1
O
2
N
N
10
5
Scheme 2 Plausible mechanism for the formation of 5.
Fig. 1 ORTEP diagram of the Xꢀray crystal structure of compound 5j with the atom numbering
scheme; thermal ellipsoids are shown at the 50% probability.

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After successful synthesis of 2ꢀpyrrolylꢀ2ꢀcyanoacetamides 5 we focussed our attention
to explore the chemical property of this substance. Therefore, as a preliminary study, 2ꢀ(4′ꢀ
acetylꢀ5ꢀmethylꢀ1,2ꢀdiphenylꢀ1Hꢀ3ꢀpyrrolyl)ꢀ2ꢀcyanoacetamide 5a was heated at reflux in
diphenyl ether to examine the formation of any cyclic product. Interestingly, a cyclic product 3ꢀ
acetylꢀ5ꢀhydroxyꢀ1ꢀphenylꢀ2ꢀmethylꢀ1Hꢀbenzo[g]indoleꢀ4ꢀcarbonitrile 11a was formed in
moderate yield (~61%) within 10 minutes through a thermal cyclization (Scheme 3). By
employing this thermal method a series of biologically important 5ꢀhydroxy benzo[g]indoles 11
were synthesized (Table 2). This novel thermal cyclization also provides an excellent
opportunity to synthesise differently substituted 5ꢀhydroxy benzo[g]indoles. Therefore we
synthesized a series of cyanoacetamide derivatives 12 following a different reaction protocol12
and converted them to the corresponding 5ꢀhydroxy benzo[g]indoles 13 by refluxing in diphenyl
ether for 10 minutes (Scheme 4, Table 3). All the compounds 11 and 13 were fully characterized
1
by H and 13C NMR data. Further determination of Xꢀray crystal structure of 3ꢀacetylꢀ5ꢀ
hydroxyꢀ1ꢀcyclopropylꢀ2ꢀmethylꢀ1Hꢀbenzo[g]indoleꢀ4ꢀcarbonitrile (11h) and 3ꢀcarboethoxyꢀ5ꢀ
hydroxyꢀ1ꢀphenylꢀ2ꢀmethylꢀ1Hꢀbenzo[g]indoleꢀ4ꢀcarbonitrile (11u) confirmed the product
formation (Fig. 2).13
O
O
R1
CN
NC
H2N
R1
HO
Diphenyl ether
O
N
R2
N
Reflux
10 min
R3
R2
R3
5
11
R1 = Ph, Me, OEt
R2 = Aryl, Benzyl, alkyl
R3 = H, Cl, OMe
Scheme 3 Synthesis of benzo[g]jndole derivatives 11 through thermal cyclization.

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Table 2 Synthesis of 5ꢀhydroxy benzo[g]jndole derivatives 11.
Entry
1
R1
Me
R2
R3
H
Starting
Product
11a
Yield(%)a
M. p.
228ꢀ230
61
55
52
53
51
59
5a
2
3
4
5
6
Me
Me
Me
Me
Me
H
H
H
H
H
238ꢀ240
212ꢀ214
253ꢀ255
247ꢀ249
140ꢀ142
5b
5c
5d
5e
5f
11b
11c
11d
11e
11f
Br
Cl
F
O
7
8
Me
Me
H
H
60
62
202ꢀ204
194ꢀ196
5g
5h
11g
11h
9
Me
Me
Me
Cl
Cl
Cl
53
51
56
270ꢀ272
238ꢀ240
178ꢀ180
5i
5j
11i
11j
11k
10
11
5k
12
Me
Cl
54
208ꢀ210
5l
11l
13
14
Me
OMe
H
52
59
188ꢀ190
218ꢀ220
5q
5u
11q
11u
CO2Et

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15
16
17
CO2Et
CO2Et
CO2Et
H
H
H
56
61
55
246ꢀ248
256ꢀ258
192ꢀ194
5v
5w
5x
11v
11w
11x
F
O
18
19
Ph
Ph
H
H
11yb
11zb
41
43
256ꢀ258
248ꢀ250
5y
5z
O
b
aIsolated Yield. For compound 11y and 11z, the yields are calculated with respect to starting
material 1
Fig. 2 ORTEP diagrams of the Xꢀray crystal structures of compounds 11h and 11u with the atom
numbering scheme; thermal ellipsoids are shown at the 50% probability.

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CN
NC
CO2Et
CO2Et
N
R
H2N
CO2Et
CO2Et
HO
Diphenyl ether
O
N
Reflux
10 min
R
12
R = Aryl
13
Scheme 4 Synthesis of 2,3ꢀdicarboethoxyꢀ5ꢀhydroxyꢀ1ꢀarylꢀ1Hꢀbenzo[g]indoleꢀ4ꢀcarbonitrile 13
through thermal cyclization.
Table 3 Synthesis of 2,3ꢀdicarboethoxyꢀ5ꢀhydroxyꢀ1ꢀarylꢀ1Hꢀbenzo[g]indoleꢀ4ꢀcarbonitrile 13.
Entry
1
R
Starting
12a
Product
13a
Yield(%)a
64
M. p.
180ꢀ182
2
3
4
5
52
61
60
63
55
168ꢀ170
238ꢀ240
194ꢀ196
180ꢀ182
176ꢀ178
12b
12c
12d
12e
12f
13b
13c
13d
13e
13f
F
Cl
O
6
a Isolated yield
After successful synthesis of various substituted 5ꢀhydroxy benzo[g]indoles 11/13 we
focussed our attention in exploring the photochemical property of this substance. Steady state
absorption and emission spectra of some of the selective compounds 11u-w have been taken in

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different solvents with varying polarity such as CH2Cl2, CH3CN and CH3OH. The concentration
of the compounds 11 was maintained at ~5 x 10ꢀ5 M. UVꢀVis absorption spectrum shows
structured band with peaks around 369 nm, 356 nm (Fig. 3a, Table 4). The emission spectrum
shows a structure less band with maxima around 408 nm (Fig. 3b, Table 4). The shape and band
position of the emission spectra are same regardless of excitation wavelength. Noticeably the
molecules display significant Stokes shift (Table 4) which indicates that the structure of the
emitting species and the ground state species are considerably different. The measured
fluorescence quantum yields (ΦF) of some of the representative compounds are found around
~0.5 which does not change much with the polarity of the solvent (Table 4).
Fig. 3 (a) UVꢀVis absorption spectra and (b) fluorescence emission spectra (λ in nm) of
representative compound 11u in different solvents ([11u] at ~5 x10ꢀ5 M conc.).

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Table 4 Spectroscopic data of 11 in three solvents
b
Compounds Solvents
λabs(nm)
λem(nm)
ΦF
Stokes shiftc
(104 cmꢀ1)
ΔE
(eV)d
a
εmax
(104 cmꢀ1molꢀ1)
CH2Cl2 370
CH3CN 369
407
406
410
404
408
407
410
407
406
0.82
0.57
0.50
0.49
0.51
0.49
0.48
0.54
0.51
0.50
0.24
0.25
0.27
0.22
0.26
0.25
0.24
0.25
0.24
3.35
3.36
3.37
3.34
3.37
3.36
3.32
3.36
3.35
11u
11v
11w
0.65
0.58
0.94
0.68
0.59
0.85
0.71
0.59
CH3OH 368
CH2Cl2 371
CH3CN 368
CH3OH 369
CH2Cl2 373
CH3CN 369
CH3OH 370
aεmax is the extinction coefficient at λmax of absorption.bFluorescence quantum yields with
reference to βꢀnaphthol in methyl cyclohexane (ΦF 0.53). cStokes shift= (1/λabsꢀ1/λem).
dDetermined from UVꢀVis absorption maximum.
The photoꢀphysical properties of the compound 11u as a ligand have been explored in
detail in presence of various metal ions Na+, Ba2+, Hg2+, Cd2+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+
in acetonitrile. The complexation of ligand 11u with Fe3+ ions in acetonitrile was accompanied
by a change of colour of the solution from colourless to yellow which was easily observed by the
nakedꢀeye (Fig. 4A). On addition of Cu2+ ions a very light green colour was developed. The
developing colour was more intense in case Fe3+ than in Cu2+ under similar conditions. The
addition of 5 equiv. of other cations as their perchlorate salts resulted in no appreciable changes
in colour under visible light (Fig. 4A). Interestingly, under UV light substantial fluorescence
quenching is observed only in presence of Fe3+ ions (Fig. 4B). UVꢀVis spectra of the ligand 11u

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in acetonitrile show no significant change on addition of metal perchlorate salts of Na+, Ba2+,
Hg2+, Cd2+, Mn2+, Co2+, Ni2+, Zn2+ (ESI, Fig. S5). However in presence of Fe3+ and Cu2+ the UVꢀ
Vis spectrum of 11u shows appreciable change compared to that of free ligand hence indicating
ligandꢀmetal interaction. On gradual addition of Fe3+ salt an absorption band develops near 400
nm with simultaneous appearance of two isobestic points at 303 nm and 380 nm (Fig. 5). The
emission spectra of ligand 11u in acetonitrile shows no change in fluorescence intensity in
presence of metal ions Na+, Ba2+, Hg2+, Cd2+, Mn2+, Co2+, Ni2+, Zn2+(Fig. 6). On the other hand
substantial quenching of ligand emission is observed in presence of Fe3+ and less extent of
quenching is observed in presence of Cu2+ (Fig. 6). The result indicates that the extent of
fluorescence quenching in Fe3+ is significantly higher compared to that of Cu2+ (Fig. 6). Further
in fluorometric titration nearly complete fluorescence quenching is observed on addition of ~ 1.2
equivalent of Fe3+ ions (Fig. 7). The high selectivity of 11u for Fe3+ may be due to the presence
of more charges (3+) on iron ions compared to that of other metal ions (2+ or 1+), which
probably causes strongest interaction with the phenolate anion. The detection limit of Fe3+ by
probe 11u has been estimated from fluorescence titration and found to be ~1.2 x 10ꢀ6 M (ESI,
Fig. S6). From the same titration, the Binding Constant of probe 11u with Fe3+ metal ion has
been measured as ~7.97 x 103 Mꢀ1 using BenesiꢀHildebrand equation (see ESI, Fig. S7). The
metal (Fe3+) to ligand (11u) binding ratio has also been calculated by jobs plot method using UV
titration and found to be in 1:1 ratio (see ESI, Fig. S8).
Subsequently the fluorescence “Turnꢀoff” sensing of probe 11u for Fe3+ ions has been
examined in presence of other metal ions. When Fe3+ ions were added to various solutions of
11u containing one of the different metal ions Co2+, Ba2+, Cd2+, Cu2+, Hg2+, Mn2+, Na+, Ni2+,
Zn2+ in acetonitrile the binding of Fe3+ ions with 11u was not significantly affected by the

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presence of these other metal ions (Fig. 8). Therefore, the intensity of the fluorescence band of
the complex [11uꢀFe3+ ] at 408 nm can be used to monitor the presence of Fe3+ ions alone as well
as Fe3+ ions in presence of other metal ions.
Fig. 4 Change in color of solution of 11u in acetonitrile in presence of 5 equiv. of each metal ion
(A) under visible light and (B) under UV light.
[11u] : [Fe3+]
2.0
1:0
1:0.2
1:0.4
1.5
1:0.6
1:0.8
1:1.0
1.0
1:1.2
1:1.5
1:2
0.5
0.0
250
300
350
400
450
500
550
Wave length (nm)
Fig. 5 Absorption spectra of 11u ([11u] = ~5 x 10ꢀ5 M) on increasing concentration of Fe3+ ions
in acetonitrile.

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11u in CH3CN
[11u] : [Na+] = 1:5
[11u] : [Ba2+] = 1:5
[11u] : [Hg2+] = 1:5
[11u] : [Cd2+] = 1:5
[11u] : [Mn2+] = 1:5
[11u] : [Fe3+] = 1:1.2
[11u] : [Co2+] = 1:5
[11u] : [Ni2+] = 1:5
[11u] : [Cu2+] = 1:5
[11u] : [Zn2+] = 1:5
500
400
300
200
100
0
Cu2+
Fe3+
400
450
Wave length (nm)
500
550
Fig. 6 Emission spectra of 11u in acetonitrile in presence of various metal ions ([11u] at 5 x10ꢀ5
M conc.).
500
[11u]:[Fe3+]
1:0
400
1:0.2
1: 0.3
1:0.4
1: 0.6
300
1:0.8
1:1.2
200
100
0
400
450
500
550
Wave length (nm)
Fig. 7 Emission spectra of 11u in acetonitrile on gradual addition of Fe 3+ ions ([11u] at 5 x10ꢀ5
M conc.).

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600
500
400
300
200
100
0
Cu2+
11u
Co2+ Ba2+ Cd2+
Hg2+ Mn2+ Na+
Ni2+
Zn2+
Metal Ions
Fig. 8 The selectivity of 11u (5x10ꢀ5 M conc.) in the presence of various metal ions in
acetonitrile. The blue bars represent the emission intensity of 11u in the presence of other metal
ions (25x10ꢀ5 M conc.). The red bars represent the emission intensity that occurs upon the
subsequent addition of Fe3+ ions (5 x10ꢀ5 M conc.) to the above solution (λem=408 nm).
In order to get more insights about the nature of Fe3+ ligand interactions 1H NMR titration
was carried out. In this experiment the perchlorate salt of Fe3+ ions was gradually added to a
DMSOꢀd6 solution of 11u. The results show that the intensity of the proton signal corresponding
to 5ꢀhydroxyl group (ꢀOH) of 11u at 10.86 ppm, which is the most probable binding site for Fe3+
ions, decreases significantly relative to that of other protons upon exposure to Fe3+ (Fig 9). This
effect proves unambiguously the formation of complex between 11u and Fe3+ ion. Additionally,
a rapid broadening and finally disappearance of the proton signal at 10.86 ppm was observed

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with gradual addition of Fe3+ ions which further confirms the fast exchange of hydroxyl (–OH)
protons due to complexation with Fe3+ ion. Moreover during the NMR titration a light yellow
colour was developed initially which gradually intensified with addition of more and more
perchlorate salt of Fe3+ ions to the DMSOꢀd6 solution of 11u indicating complexation between
Fe3+ ion and 11u. The UVꢀVis and NMR data clearly suggest that the phenolic hydroxyl groups
(ꢀOH) of 11u are deprotonated due to complexation with Fe3+ ions which is probably responsible
for strong fluorescence quenching.

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(a)
(b)
(c)
(d)
Fig. 9 Change in 1H NMR spectra of 11u upon addition of Fe3+ ions, (a)00 equiv., (b) 0.5 equiv.,
(c) 1.0 equiv., and (d) 2.0 equiv. in [d6]ꢀDMSO.

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Conclusions
In conclusion, a convenient two steps methodology has been developed for the synthesis of
biologically important 5ꢀhydroxy benzo[g]indoles from various easily available 1,3ꢀdicarbonyl
compounds, amines, arylglyoxals and malononitrile under metal free conditions. The present
synthetic protocol is quite atom economical in nature since only two molecules of water and one
molecule of ammonia are released during the course of the reactions. The synthesised 5ꢀhydroxy
benzo[g]indoles show fluorescence activity with good quantum yields (ΦF = ~ 0.50) and ability
to act as fluorescence “Turnꢀoff” sensor for Fe3+ ions. The interaction of 5ꢀhydroxy
benzo[g]indoles with Fe3+ ions can also be monitored through UVꢀVis spectral change and
nakedꢀeye colour change in the presence and absence of UV radiation. Thus, the sensing of 5ꢀ
hydroxy benzo[g]indoles for iron at the low level (detection limit = ~1.2 x 10ꢀ6 M) may have
potential applications in current biomedical and pathological research works. It is also worth
mentioning that phenolics containing ironꢀbinding motifs have also been identified in many bioꢀ
active plants such as grapes, tea and traditional Chinese medicine plants.
EXPERIMENTAL SECTION
General: Arylglyoxals 3 were prepared from corresponding acetophenones by oxidation with
selenium dioxide in dioxane.14 Solvents were purchased from commercial suppliers and used
after distillation. Melting points were determined in open capillary tubes and are uncorrected. IR
1
13
spectra were recorded with a PerkinꢀElmer 782 spectrophotometer. H (300 MHz) and C (75
MHz) NMR spectra were recorded in DMSOꢀd6 with a Bruker 300 MHz instrument. Elemental
analyses (C, H and N) were performed by using a PerkinꢀElmer 240C elemental analyzer. The

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Xꢀray diffraction study of crystallized compounds was performed with Bruker APEXꢀII CCD
system.
2-pyrrolyl-2-cyanoacetamides5a-z; General Procedure: A mixture of 1,3ꢀdicarbonyl
compound 1 (1.0 mmol) and amine 2 (1.0 mmol) in ethanol (20 mL) was heated for 2 minutes.
Then to the above hot mixture, arylglyoxal 3 (1.0 mmol) and malononitrile 4 (1.3 mmol) were
added and the reaction mixture was heated at reflux for 10 minutes. After completion of the
reaction (monitored by TLC analysis), the solvent was removed under reduced pressure. The
resulting solid residues were purified by column chromatography (EtOAc–hexane) on silica gel
to get the light yellow solid products 5.
2-(4-Acetyl-5-methyl-1,2-diphenyl-1H-3-pyrrolyl)-2-cyanoacetamide (5a). Light yellow
solid; yield: 282 mg (79%); m.p.: 160ꢀ162 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.40ꢀ7.30 (m,
4H), 7.28ꢀ7.21 (m, 5H), 7.12ꢀ7.07 (m, 3H), 4.73 (s, 1H), 2.47 (s, 3H), 2.33 (s, 3H) ppm; 13C
NMR (75 MHz, DMSOꢀd6): δ =193.8, 166.6, 137.3, 136.7, 135.3, 131.1, 130.0, 129.5, 129.3,
129.0, 128.6, 128.5, 120.4, 117.9, 111.8, 37.2, 31.1, 14.2 ppm; IR (KBr): 2378, 1705, 1650 cmꢀ1;
Anal calcd for C22H19N3O2: C, 73.93; H, 5.36; N, 11.76% Found C, 73.85; H, 5.30; N, 11.69%.
2-(4-Acetyl-5-methyl-2-phenyl-1ꢀp-tolyl-1H-3-pyrrolyl)-2-cyanoacetamide (5b). Light yellow
solid; yield: 281 mg (76%); m.p.: 168ꢀ170 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.37 (s, 1H),
7.31ꢀ7.24 (m, 3H), 7.22ꢀ7.12 (m, 6H), 7.06 (s, 1H), 4.73 (s, 1H), 2.47 (s, 3H), 2.32 (s, 3H), 2.25
(s, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ =193.8, 166.6, 138.4, 136.8, 135.4, 134.7, 131.1,
130.1, 129.9, 128.9, 128.6, 128.5, 120.3, 117.9, 111.7, 37.2, 31.3, 21.0, 14.3 ppm; IR (KBr):
2376, 1708, 1647 cmꢀ1; Anal calcd for C23H21N3O2: C, 74.37; H, 5.70; N, 11.31% Found C,
74.30; H, 5.62; N, 11.23%.

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2-[4-Acetyl-5-methyl-1-(4-bromophenyl)-2-phenyl-1H-3-pyrrolyl]-2-cyanoacetamide (5c).
Light yellow solid; yield: 317 mg (73%); m.p.: 146ꢀ148 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.58 (d, J = 5.4 Hz, 2H), 7.38 (s, 1H), 7.27ꢀ7.17(m, 5H), 7.13ꢀ7.10 (m, 2H), 7.05 (s, 1H), 4.69 (s,
1H), 2.47 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ =193.8, 166.5, 136.7,
135.2, 132.5, 131.4, 131.1, 129.8, 128.8, 128.7, 122.2, 120.6, 117.8, 112.0, 107.8, 37.1, 31.1,
14.2 ppm; IR (KBr): 2370, 1701, 1649 cmꢀ1; Anal calcd for C22H18BrN3O2: C, 60.56; H, 4.16; N,
9.63% Found C, 60.48; H, 4.10; N, 9.55%.
2-[4-Acetyl-5-methyl-1-(4-chlorophenyl)-2-phenyl-1H-3-pyrrolyl]-2-cyanoacetamide (5d).
Light yellow solid; yield: 289 mg (74%); m.p.: 180ꢀ182 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.46ꢀ7.40 (m, 4H), 7.28ꢀ7.21 (m, 4H), 7.16ꢀ7.14(m, 2H), 7.08 (s, 1H), 4.74 (s, 1H), 2.50 (s, 3H),
13
2.36 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ =193.8, 166.6, 136.7, 136.3, 135.3, 133.7,
131.2, 129.8, 129.5, 128.7, 120.6, 117.9, 112.0, 37.2, 31.2, 14.2 ppm; IR (KBr): 2372, 1704,
1647 cmꢀ1; Anal calcd for C22H18ClN3O2: C, 67.43; H, 4.63; N, 10.72% Found C, 67.34; H, 4.55;
N, 10.65%.
2-[4-Acetyl-5-methyl-1-(4-fluorophenyl)-2-phenyl-1H-3-pyrrolyl]-2-cyanoacetamide (5e).
Light yellow solid; yield: 266 mg (71%); m.p.: 218ꢀ220 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.40ꢀ7.36 (m, 2H), 7.28ꢀ7.20 (m, 6H), 7.15ꢀ7.13(m, 2H), 7.07 (s, 1H), 4.73 (s, 1H), 2.49 (s, 3H),
13
2.35 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ =193.8, 166.6, 163.5, 160.3, 136.9, 135.5,
133.7, 133.6, 131.5, 131.2, 129.9, 128.8, 128.6, 120.4, 117.9, 116.5, 116.2, 111.8, 37.2, 31.1,
14.2 ppm; IR (KBr): 2371, 1701, 1652 cmꢀ1; Anal calcd for C22H18FN3O2: C, 70.39; H, 4.83; N,
11.19% Found C, 70.31; H, 4.76; N, 11.12%.

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2-[4-Acetyl-5-methyl-1-(4-methoxyphenyl)-2-phenyl-1H-3-pyrrolyl]-2-cyanoacetamide (5f).
Light yellow solid; yield: 317 mg (82%); m.p.: 162ꢀ164 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.33 (s, 1H), 7.27ꢀ7.21 (m, 4H), 7.15ꢀ7.12 (m, 3H), 7.05 (s, 1H), 6.92(d, J = 8.7 Hz, 2H), 4.72 (s,
1H), 3.73 (s, 3H), 2.48 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 193.8,
166.6, 159.3, 137.0, 135.5, 131.2, 130.3, 130.2, 128.6, 128.5, 120.2, 118.0, 116.5, 114.6, 114.6,
111.6, 55.7, 37.2, 31.1, 14.2 ppm; IR (KBr): 2370, 1706, 1656 cmꢀ1; Anal calcd for C23H21N3O3:
C, 71.30; H, 5.46; N, 10.85% Found C, 71.22; H, 5.38; N, 10.77%.
2-(4-Acetyl-5-methyl-1-benzyl-2-phenyl-1H-3-pyrrolyl)-2-cyanoacetamide (5g). Light yellow
solid; yield: 285 mg (77%); m.p.: 196ꢀ198 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.32ꢀ7.31 (m,
3H), 7.23ꢀ7.11 (m, 6H), 6.88ꢀ6.84 (m, 3H), 4.97 (s, 2H), 4.70 (s, 1H), 2.35 (s, 3H), 2.33 (s, 3H)
ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 194.0, 166.5, 137.6, 136.1, 135.0, 131.2, 129.8, 129.5,
129.1, 127.7, 126.1, 120.5, 118.1, 111.7, 47.7, 37.0, 31.3, 13.4 ppm; IR (KBr): 2375, 1703, 1646
cmꢀ1; Anal calcd for C23H21N3O2: C, 74.37; H, 5.70; N, 11.31% Found C, 74.30; H, 5.64; N,
11.24%.
2-(4-Acetyl-5-methyl-1-cyclopropyl-2-phenyl-1H-3-pyrrolyl)-2-cyanoacetamide (5h). Light
yellow solid; yield: 260 mg (81%); m.p.: 166ꢀ168 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.49ꢀ
7.44 (m, 3H), 7.41ꢀ7.35 (m, 2H), 7.25 (s, 1H), 6.84 (s, 1H), 4.68 (s, 1H), 3.26ꢀ3.20 (m, 1H), 2.67
13
(s, 3H), 2.42 (s, 3H), 0.77ꢀ0.69 (m, 2H), 0.44ꢀ0.43 (m, 2H) ppm; C NMR (75 MHz, DMSOꢀ
d6): δ = 193.5, 166.7, 138.7, 135.6, 130.9, 130.7, 128.8, 128.7, 119.7, 118.0, 110.7, 37.0, 31.2,
27.5, 14.2, 9.6, 9.5 ppm; IR (KBr): 2371, 1701, 1652 cmꢀ1; Anal calcd for C19H19N3O2: C, 71.01;
H, 5.96; N, 13.08% Found C, 69.92; H, 5.90; N, 13.01%.

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2-[4-Acetyl-5-methyl-1-phenyl-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-cyanoacetamide
(5i).
Light yellow solid; yield: 285 mg (73%); m.p.: 118ꢀ120 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.39ꢀ7.34 (m, 4H), 7.33ꢀ7.31 (m, 4H), 7.16ꢀ7.13(m, 3H), 4.90 (s, 1H), 2.49 (s, 3H), 2.35 (s, 3H)
ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 194.1, 166.5, 137.1, 136.9, 133.9, 133.6, 133.0, 129.6,
129.2, 129.1, 128.6, 120.5, 117.9, 112.2, 36.9, 31.2, 14.2 ppm; IR (KBr): 2372, 1704, 1647 cmꢀ1;
Anal calcd for C22H18ClN3O2: C, 67.43; H, 4.63; N, 10.72% Found C, 67.35; H, 4.54; N, 10.63%.
2-[4-Acetyl-5-methyl-1-p-tolyl-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-cyanoacetamide
(5j).
Light yellow solid; yield: 292 mg (72%); m.p.: 198ꢀ200 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.39 (s, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.22ꢀ7.13 (m, 7H), 4.88 (s, 1H), 2.48 (s, 3H), 2.33 (s, 3H),
13
2.30 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 194.0, 166.5, 138.7, 137.0, 134.5, 133.9,
133.6, 133.0, 130.1, 129.1, 128.9, 128.6, 120.4, 112.1, 107.8, 36.9, 31.2, 21.0, 14.2 ppm; IR
(KBr): 2376, 1707, 1649 cmꢀ1; Anal calcd for C23H20ClN3O2: C, 68.06; H, 4.97; N, 10.35%
Found , 67.98; H, 4.91; N, 10.27%.
2-[4-Acetyl-5-methyl-1-benzyl-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-cyanoacetamide (5k).
Light yellow solid; yield: 296 mg (73%); m.p.: 150ꢀ152 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.47 (d, J = 8.4 Hz, 2H), 7.31ꢀ7.24 (m, 6H), 7.07 (s, 1H), 6.93 (d, J = 7.2 Hz, 2H), 5.06 (s, 2H),
13
4.97 (s, 1H), 2.46 (s, 3H), 2.43 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 194.2, 166.4,
137.5, 136.3, 134.4, 133.5, 133.1, 129.1, 128.8, 127.7, 126.0, 120.6, 118.0, 112.2, 47.7, 36.6,
31.4, 13.4 ppm; IR (KBr): 2375, 1704, 1653 cmꢀ1; Anal calcd for C23H20ClN3O2: C, 68.06; H,
4.97; N, 10.35% Found , 67.95; H, 4.90; N, 10.28%.
2-[4-Acetyl-5-methyl-1-cyclopropyl-2-(4'-chlorophenyl)-1H-3-pyrrolyl]-2-cyanoacetamide
1
(5l). Light yellow solid; yield: 281 mg (79%); m.p.: 184ꢀ186 ºC; H NMR (300 MHz, DMSOꢀ

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d6): δ = 7.31 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 7.07 (s 1H), 6.70 (s, 1H), 4.61 (s, 1H),
13
3.05ꢀ3.02 ( m, 1H), 2.46 (s, 3H), 2.21 (s, 3H), 0.62ꢀ0.58 (m, 2H), 0.25ꢀ0.23 (m, 2H) ppm; C
NMR (75 MHz, DMSOꢀd6): δ = 193.7, 166.6, 139.0, 134.3, 133.5, 132.6, 129.9, 128.8, 119.8,
117.9, 111.2, 36.7, 31.4, 27.5, 14.5, 14.2, 9.6 ppm; IR (KBr): 2370, 1702, 1657 cmꢀ1; Anal calcd
for C19H18ClN3O2: C, 64.13; H, 5.10; N, 11.81% Found , C, 64.07; H, 5.04; N, 11.74%.
2-[4-Acetyl-5-methyl-1-(4-bromophenyl)-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-
1
cyanoacetamide (5m). Light yellow solid; yield: 347 mg (74%); m.p.: 240ꢀ242 ºC; H NMR
(300 MHz, DMSOꢀd6): δ = 7.64ꢀ7.61 (m, 2H), 7.41 (s, 1H), 7.37ꢀ7.35 (m, 2H), 7.30ꢀ7.22 (m,
2H), 7.17ꢀ 7.11 (m, 3H), 4.87 (s, 1H), 2.49 (s, 3H), 2.35 (s, 3H) ppm; 13C NMR (75 MHz,
DMSOꢀd6): δ = 194.0, 166.5, 136.9, 133.8, 133.0, 132.6, 131.4, 128.8, 122.4, 120.7, 117.8, 112.4,
36.9, 31.2, 14.2 ppm; IR (KBr): 2371, 1709, 1643 cmꢀ1; Anal calcd for C22H17BrClN3O2: C,
56.13; H, 3.64; N, 8.93% Found C, 56.06; H, 3.58; N, 8.85%.
2-[4-Acetyl-5-methyl-1,2-bis-(4-chlorophenyl)-1H-3-pyrrolyl]-2-cyanoacetamide (5n). Light
yellow solid; yield: 302 mg (71%); m.p.: 244ꢀ246 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.47
(d, J = 8.7 Hz, 2H), 7.41 (s, 1H), 7.35ꢀ7.26 (m, 4H), 7.14ꢀ7.10 (m, 3H), 4.84 (s, 1H), 2.47 (s, 3H),
13
2.33 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 194.0, 166.5, 137.0, 136.0, 133.9, 133.8,
133.0, 131.2, 131.1, 129.7, 128.8, 120.7, 117.8, 112.4, 36.9, 31.2, 14.2 ppm; IR (KBr): 2367,
1702, 1648 cmꢀ1; Anal calcd for C22H17Cl2N3O2: C, 61.98; H, 4.02; N, 9.86% Found C, 61.91; H,
3.95; N, 9.80%.
2-[4-Acetyl-5-methyl-1-(4-fluorophenyl)-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-
1
cyanoacetamide (5o). Light yellow solid; yield: 295 mg (72%); m.p.: 205ꢀ207 ºC; H NMR
(300 MHz, DMSOꢀd6): δ = 7.41ꢀ7.26 (m, 7H), 7.17ꢀ7.12 (m, 3H), 4.88 (s, 1H), 2.50 (s, 3H), 2.35

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(s, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 194.0, 166.5, 137.1, 134.0, 133.7, 133.4, 133.0,
131.5, 128.9, 128.7, 120.5, 117.8, 116.7, 116.4, 112.2, 36.9, 31.2, 14.2 ppm; IR (KBr): 2371,
1709, 1643 cmꢀ1; Anal calcd for C22H17ClFN3O2: C, 64.47; H, 4.18; N, 10.25% Found C, 64.41;
H, 4.12; N, 10.18%.
2-[4-Acetyl-5-methyl-1-(4-methoxyphenyl)-2-(4-chlorophenyl)-1H-3-pyrrolyl]-2-
1
cyanoacetamide (5p). Light yellow solid; yield: 320 mg (76%); m.p.: 208ꢀ210 ºC; H NMR
(300 MHz, DMSOꢀd6): δ = 7.39ꢀ7.32 (m, 3H), 7.20ꢀ7.11 (m, 5H), 6.94 (d, J = 8.1 Hz, 2H), 4.88
(s, 1H), 3.74 (s, 3h), 2.48 (s, 3H), 2.33 (s, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 194.0,
166.6, 159.4, 137.2, 134.1, 133.6, 133.0, 130.4, 130.3, 129.7, 129.2, 128.6, 120.3, 117.9, 114.7,
112.0, 55.7, 36.9, 31.2, 14.2 ppm; IR (KBr): 2375, 1702, 1640 cmꢀ1; Anal calcd for
C23H20ClN3O3: C, 65.48; H, 4.78; N, 9.96% Found C, 65.41; H, 4.72; N, 9.89%.
2-[4-Acetyl-5-methyl-1-phenyl-2-(4-methoxyphenyl)-1H-3-pyrrolyl]-2-cyanoacetamide (5q).
Light yellow solid; yield: 313 mg (81%); m.p.: 164ꢀ166 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ =
7.38ꢀ7.30 (m, 4H), 7.28ꢀ7.23 (m, 2H), 7.05ꢀ7.02 (m, 3H), 6.79(d, J = 8.7 Hz, 2H), 4.71 (s, 1H),
13
3.66 (s, 3H), 2.47 (s, 3H), 2.31 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 193.8, 166.7,
159.4, 137.4, 136.4, 135.2, 132.5, 129.5, 129.0, 122.0, 120.3, 118.0, 114.0, 111.6, 55.4, 37.2,
31.1, 14.2 ppm; IR (KBr): 2369, 1701, 1655 cmꢀ1; Anal calcd for C23H21N3O3: C, 71.30; H, 5.46;
N, 10.85% Found C, 71.21; H, 5.36; N, 10.75%.
2-[4-Acetyl-5-methyl-1-(4-chlorophenyl)-2-(4-methoxyphenyl)-1H-3-pyrrolyl]-2-
cyanoacetamide (5r). Light yellow solid; yield: 316 mg (75%); m.p.: 198ꢀ200 ºC; 1H NMR (300
MHz, DMSOꢀd6): δ = 7.48ꢀ7.25 (m, 5H), 7.07ꢀ6.98 (m, 3H), 6.92ꢀ6.82 (m, 2H), 4.70 (s, 1H),
13
3.69 (s, 3H), 2.47 (s, 3H), 2.33 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 193.5, 166.4,

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DOI: 10.1039/C5RA05780A
159.3, 136.2, 135.0, 133.4, 132.3, 130.9, 129.3, 128.6, 121.5, 120.2, 117.7, 113.9, 111.6, 55.2,
37.0, 30.9, 13.9 ppm; IR (KBr): 2371, 1704, 1643 cmꢀ1; Anal calcd for C23H20ClN3O3: C, 65.48;
H, 4.78; N, 9.96% Found C, 65.40; H, 4.71; N, 9.87%.
2-[4-Acetyl-5-methyl-1-benzyl -2-(4-methoxyphenyl)-1H-3-pyrrolyl]-2-cyanoacetamide (5s).
1
Light yellow solid; yield: 312 mg (78%); m.p.: 88ꢀ90 ºC; H NMR (300 MHz, DMSOꢀd6): δ =
7.33ꢀ7.28 (m, 4H), 7.25ꢀ7.17 (m, 2H), 6.97ꢀ6.95 (m, 5H), 5.04 (s, 2H), 4.78 (s, 1H), 3.74 (s, 3H),
13
2.43 (s, 3H), 2.40 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ = 193.7, 166.4, 159.9, 137.5,
135.6, 134.7, 132.4, 128.9, 127.4, 125.9, 121.5, 120.2, 117.9, 114.3, 111.5, 55.3, 36.8, 31.1, 13.2
ppm; IR (KBr): 2374, 1705, 1657 cmꢀ1; Anal calcd for C24H23N3O3: C, 71.80; H, 5.77; N,
10.47% Found , C, 71.72; H, 5.71; N, 10.40%.
2-[4-Acetyl-5-methyl-1-cyclopropyl-2-(4-methoxyphenyl)-1H-3-pyrrolyl]-2-cyano
acetamide (5t). Light yellow solid; yield: 284 mg (81%); m.p.: 152ꢀ154 ºC; 1H NMR (300 MHz,
DMSOꢀd6): δ = 7.68 (d, J = 8.1 Hz, 3H), 7.01 (d, J = 7.8 Hz, 2H), 6.82 (s, 1H), 4.65 (s, 1H), 3.78
(s, 3H), 3.20ꢀ3.10 ( m, 1H), 2.65 (s, 3H), 2.40 (s, 3H), 0.92ꢀ0.90 (m, 2H), 0.46ꢀ0.44 (m, 2H)
ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 193.5, 166.7, 159.5, 138.4, 135.6, 132.1, 123.0, 119.6,
118.1, 114.2, 110.6, 55.5, 37.0, 31.2, 27.4, 14.1, 9.4 ppm; IR (KBr): 2368, 1704, 1652 cmꢀ1; Anal
calcd for C20H21N3O3: C, 68.36; H, 6.02; N, 11.96% Found , C, 68.28; H, 5.94; N, 11.90%.
2-(4-Carboethoxy-5-methyl-1,2-diphenyl-1H-3-pyrrolyl)-2-cyanoacetamide (5u). Light
yellow solid; yield: 302 mg (78%); m.p.: 164ꢀ166 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 7.45
(s, 1H), 7.30ꢀ7.27 (bs, 4H), 7.18ꢀ7.17 (m, 4H), 7.09ꢀ7.05 (m, 3H), 4.57 (s, 1H), 4.18ꢀ4.11 (m,
2H), 2.41 (s, 3H), 1.25ꢀ1.20 (m, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 161.0, 158.7,
132.3, 131.5, 129.3, 125.3, 124.2, 123.7, 123.2, 122.8, 122.5, 112.4, 105.8, 104.3, 53.9, 31.7, 9.2,

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7.8 ppm; IR (KBr): 2251, 1701, 1690 cmꢀ1; Anal calcd for C23H21N3O3: C, 71.30; H, 5.46; N,
10.85% Found C, 71.22; H, 5.39; N, 10.78%.
2-[4-Carboethoxy-5-methyl-1-(4-fluorophenyl)-2-phenyl-1H-3-pyrrolyl]-2-cyanoacetamide
1
(5v). Light yellow solid; yield: 303 mg (75%); m.p.: 194ꢀ196 ºC; H NMR (300 MHz, DMSOꢀ
d6): δ = 7.55 (s, 1H), 7.46 (s, 1H), 7.35ꢀ7.21 (m, 6H), 7.16ꢀ7.11 (m, 3H), 4.65 (s, 1H), 4.27ꢀ4.20
(m, 2H), 2.32 (s, 3H), 1.39ꢀ1.28 (m, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ = 166.4, 164.0,
159.9, 138.0, 134.8, 133.3, 130.9, 130.7, 129.5, 128.4, 128.3, 117.8, 116.1, 115.8, 111.2, 109.8,
59.4, 37.1, 14.1, 12.4 ppm; IR (KBr): 2250, 1702, 1688 cmꢀ1; Anal calcd for C23H20FN3O3: C,
68.14; H, 4.97; N, 10.36% Found C, 68.07; H, 4.91; N, 10.30%.
2-[4-Carboethoxy-5-methyl-1-(4-methoxyphenyl)-2-phenyl-1H-3-pyrrolyl]-2-
cyanoacetamide (5w). Light yellow solid; yield: 329 mg (79%); m.p.: 216ꢀ218 ºC; 1H NMR
(300 MHz, DMSOꢀd6): δ = 7.51 (s, 1H), 7.28ꢀ7.27 (m, 4H), 7.16ꢀ7.14 (m, 4H), 6.92ꢀ6.90 (m,
2H), 4.62 (s, 1H), 4.26ꢀ4.19 (m, 2H), 3.72 (s, 3H), 2.30 (s, 3H), 1.33ꢀ1.28 (m, 3H) ppm; 13C
NMR (75 MHz, DMSOꢀd6): δ = 166.4, 164.1, 158.9, 138.1, 134.9, 130.7, 129.8, 129.5, 128.3,
117.8, 114.1, 110.9, 109.5, 59.3, 55.3, 37.1, 14.1, 12.5 ppm; IR (KBr): 2253, 1703, 1693 cmꢀ1;
Anal calcd for C24H23N3O4: C, 69.05; H, 5.55; N, 10.07% Found C, 68.98; H, 5.49; N, 10.01%.
2-(4-Carboethoxy-5-methyl-1-benzyl-2-phenyl-1H-3-pyrrolyl)-2-cyanoacetamide (5x). Light
1
yellow solid; yield: 293 mg (73%); m.p.: 78ꢀ80 ºC; H NMR (300 MHz, DMSOꢀd6): δ = 7.51ꢀ
7.43 (m, 4H), 7.33ꢀ7.23 (m, 5H), 7.05 (s, 1H), 7.95 ( d, J = 7.2 Hz, 2H), 5.04 (s, 2H), 4.64 (s,
1H), 4.23ꢀ4.17 (m, 2H), 2.40 (s, 3H), 1.32ꢀ1.24 (m, 3H) ppm; 13C NMR (75 MHz, DMSOꢀd6): δ
= 166.2, 164.1, 137.1, 134.3, 130.8, 129.5, 129.1, 128.8, 128.7, 127.2, 125.7, 117.9, 111.2, 109.7,

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59.2, 47.3, 36.9, 14.0, 11.5 ppm; IR (KBr): 2248, 1701, 1688cmꢀ1; Anal calcd for C24H23N3O3: C,
71.80; H, 5.77; N, 10.47% Found C, 71.73; H, 5.72; N, 10.41%.
Benzo[g]jndole 11; General Procedure: The 2ꢀpyrrolylꢀ2ꢀcyanoacetamide 5 (0.5 mmol) in
diphenyl ether (10 mL) was heated at reflux for 10 minutes. Upon completion of the reaction, the
crude mass was purified by chromatography on a silica gel column (EtOAc/hexane, 1:1) to get
pure compound 11 as brown solid.
3-Acetyl-5-hydroxy-1-phenyl-2-methyl-1H-benzo[g]indole-4-carbonitrile (11a). Brown solid;
yield: 103 mg (61%); m.p.: 228ꢀ230 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 10.91 (s, 1H), 8.35
(d, J = 8.4 Hz, 1H), 7.73ꢀ7.20 (m, 3H), 7.53 (t, J = 3.6 Hz, 2H), 7.44 (t, J = 7.5 Hz, 1H), 7.30 (t,
13
J = 7.2 Hz, 1H), 6.86 (d, J = 8.7Hz, 1H), 2.62 (s, 3H), 2.28 (s, 3H) ppm; C NMR (75 MHz,
DMSOꢀd6): δ = 195.9, 156.4, 140.5, 138.9, 131.0, 130.5, 129.2, 125.4, 124.8, 124.7, 123.2, 120.5,
119.4, 118.0, 117.1, 88.6, 32.6, 12.9 ppm; IR (KBr): 3330, 2214, 1647 cmꢀ1; Anal calcd for
C22H16N2O2: C, 77.63; H, 4.74; N, 8.23% Found, C, 77.56; H, 4.67; N, 8.16%.
3-Acetyl-5-hydroxy-1-p-tolyl-2-methyl-1H-benzo[g]indole-4-carbonitrile (11b). Brown solid;
1
yield: 97 mg (55%); m.p.: 238ꢀ240 ºC; H NMR (300 MHz, DMSOꢀd6): δ = 10.89 (s, 1H), 8.35
(d, J = 8.1 Hz, 1H), 7.53ꢀ7.50 (m, 1H), 7.46ꢀ7.30 (m, 3H), 7.53 (t, J = 3.6 Hz, 2H), 6.96 (d, J =
13
8,4 Hz, 1H), 2.61 (s, 3H), 2.50 (s, 3H), 2.26 (s, 3H) ppm; C NMR (75 MHz, DMSOꢀd6): δ =
195.9, 156.4, 140.7, 140.1, 136.2, 131.4, 129.3, 128.9, 125.5, 124.7, 124.5, 123.2, 120.6, 119.3,
117.9, 117.1, 88.6, 32.6, 21.3, 12.9 ppm; IR (KBr): 3334, 2216, 1648 cmꢀ1; Anal calcd for
C23H18N2O2: C, 77.95; H, 5.12; N, 7.90 Found , C, 77.88; H, 5.05; N, 7.83.
3-Acetyl-5-hydroxy-1-(4-bromophenyl)-2-methyl-1H-benzo[g]indole-4-carbonitrile (11c).
Brown solid; yield: 109 mg (52%); m.p.: 212ꢀ214 ºC; 1H NMR (300 MHz, DMSOꢀd6): δ = 10.96