Synthesis of solid state fluorescent quino[2,3-b]carbazoles via copper(II) triflate-catalyzed heteroannulation: Application to detection of TNT

Article abstract of DOI:10.1016/j.tet.2013.07.016

New analogues of solid state fluorescent quino[2,3-b]carbazoles have been synthesized from heteroannulation of quinoline alkynylaldehyde and indole. Their preliminary photophysical properties are studied and application as chemosensory material for detect

Full text of DOI:10.1016/j.tet.2013.07.016

Tetrahedron 69 (2013) 8269e8275
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Synthesis of solid state fluorescent quino[2,3-b]carbazoles via
copper(II) triflate-catalyzed heteroannulation: application to
detection of TNT
*
K.S. Prakash, Rajagopal Nagarajan
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
a r t i c l e i n f o
a b s t r a c t
Article history:
New analogues of solid state fluorescent quino[2,3-b]carbazoles have been synthesized from hetero-
annulation of quinoline alkynylaldehyde and indole. Their preliminary photophysical properties are
studied and application as chemosensory material for detection of trinitrotoluene is explored.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 15 April 2013
Received in revised form 3 July 2013
Accepted 4 July 2013
Available online 12 July 2013
Keywords:
Quino[2,3-b]carbazoles
Solid state fluorescent compounds
Indole heteroannulation
Copper(II) triflate
TNT sensors
1. Introduction
performance organic semiconductors are suitable for organic
thin-film transistor applications and organic solar cells (OSCs).3b
Carbazole nucleus forms a basic skeleton of various alkaloids
and they are found to have a wide range of biological activities.
Among these, heteroaryl-annulated carbazoles are one of the at-
tractive class of compounds due to their biological activities.1 Their
The applications of fluorescent scaffolds have been extensively
reviewed in literature,4aek e.g., intracellular pH indicators,4b sen-
sors for reactive oxygen and nitrogen species,4c metal sensors,4deh
detection of nitric oxide (NO) in living systems5 and hydrogen
peroxide (H2O2) inside living cells,6 as well as chemosensor for
detection of high explosives7aeo (commonly, 2,4,6-trinitrotoluene
(TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX) and pentaerythritol
tetranitrate (PETN)).
Now a days, considerable effort has been paid to the de-
velopment of fluorescence-sensors;8 especially in the detection of
nitroaromatics. Swager group showed that pentiptycene-derived
conjugated polymer is an excellent fluorescent chemosensor for
the detection of nitroaromatics.7i Most recently, Ajayaghosh et al.
demonstrated the attogram level detection of TNT,7g and Pradeep
group has reported a simple and reliable strategy for detection of
TNT and Hg2þ at sub-zeptomole level.7m
Over the past few years, there are amazing findings in the an-
nulations involving phenylacetylenes bearing a carbonyl group or
an imino group in the ortho position are explored, and this protocol
is being used as an extremely rapid and powerful approach for the
synthesis of carbocyclic and heterocyclic compounds.9aem How-
ever, to the best of our knowledge synthesis of solid state fluores-
cent quinocarbazoles is not reported. We envisioned that quino
[2,3-b]carbazoles would be obtained by cyclization of indole and
biological significance and synthetic importance have been exten-
1a
€
sively reviewed by Knolker et al. Pyrido[4,3-b]carbazole (ellipti-
cine, olivacine and their derivatives) and quinolino[4,3-b]carbazole
alkaloids (calothrixin A and its N-deoxy derivative, calothrixin B)
are naturally occurring important biologically active molecules.1a
Furthermore, staurosporine-inspired metallo-pyridocarbazole
scaffolds are useful in designing selective inhibitors for various
kinases of human kinome,2a GSK3,2bee Pim1,2def MSK1,2d PAK12g
and also in the binding of ATP.2h
Carbazole-based compounds are being used in the field of or-
ganic electronics. For example, carbazole-based donor-acceptor
compounds (1,2-dicyano-trans-1,2-bis-4-(carbazolyl)phenylethyle
ne, 1,2-dicyano-trans-1,2-bis-4-(3,6-di-tert-butylcarbazolyl)phenyl
ethylene),3a hole-transport molecule to afford highly efficient Or-
ganic Light Emitting Diodes (OLEDs),3c organic field-effect tran-
sistors,3d host materials for triplet emitters in OLEDs,3e,f high-
* Corresponding author. Tel.: þ91 40 23134831; fax: þ91 40 23012460; e-mail
addresses: rnsc@uohyd.ernet.in, naga_indole@yahoo.co.in (R. Nagarajan).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.016

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K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
quinoline alkynylaldehyde.11c Interestingly, N-protected quino[2,3-
b]carbazoles show bright green emission in liquid and red emission
in solid state (Fig. 2). While adding trace amount of nitrobenzene,
sensing was observed by naked eye. With this view point, we
studied fluorescent sensing in various nitroaromatics and TNT.
Herein, we report the first solid state fluorescent quino[2,3-b]car-
bazoles synthesized from copper(II) triflate-catalyzed hetero-
annulation and their sensing response to TNT.
metal catalysts and solvents. The results are summarized in opti-
mization Table 1.
While using Cu(OTf)2 (5 mol %) and 1,2-dichloroethane as sol-
vent, the expected quinocarbazole (QC) is formed only in 35% yield
Table 1
Optimization of reaction conditionsa
Entry
Catalyst
Solvent
Time (h)/temp (ꢀC)
Yieldb (%)
1
2
3
4
5
6
7
8
Cu(OTf)2
CuBr
CuCl
DCE
DCE
DCE
DCE
10/80
10/80
10/80
10/80
10/80
10/80
10/80
12/100
12/120
6/120
6/120
6/120
12/80
24/120
10/120
35
30
20
35
30
20
25
35
51
63
60
53
40
NR
25
CuI
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
CuI
DCM
THF
Dioxane
Toluene
DMF
DMA
DMA
DMA
CH3CN
DMA
DMA
9
10
11
12
13
14
15
Cu(OTf)2
d
CuCl2
a
Reaction conditions: 1a (0.5 mmol), N-methyl indole (0.5 mmol) and solvent
5.0 mL. Catalyst 5 mol %.
b
Isolated yields. [NR] No reaction. Optimized reaction condition is in bold.
(Table 1, entry 1). Other copper catalysts CuCl, CuBr, CuI and CuCl2
did not improve the yield of the product (Table 1, entries 2e4 and
entry 15). Screening various metal catalysts also gave only inferior
results (La(OTf)3, Sc(OTf)3, Yb(OTf)3). However, we also screened
other solvents. Gratifyingly, when DMA (as solvent) and 5 mol % of
copper(II) triflate were employed, the yield of expected product
was significantly enhanced to 63% after 6 h heating at 120 ꢀC (Table
1, entry 10). Reaction did not occur in absence of catalyst. By using
the above mentioned optimized reaction conditions, the substrate
scope of the heteroannulation and the optical properties of the
products were studied (Table 2). The yield was decreased, when
unprotected indoles were used as substrate (3a, 3b, 3h and 3i). No
reaction occurred, when reaction occurred between N-sulfony-
lindole and 1a. The structures of compounds 3a, 3e and 3l were
also unambiguously confirmed by single-crystal X-ray diffraction
analysis (Fig. 1).10
Fig. 1. ORTEP diagrams of 3a, 3e and 3l. Hydrogen atoms are omitted for clarity.
Based on the literature,11 the mechanism for formation of
products is explained in Scheme 1. As depicted in Scheme 1, cop-
per(II) triflate activates the triple bond and then 6-endo-dig cycli-
zation leads to the formation of indol-3-yl-pyrano[4,3-b]quinoline
(I). Subsequent electrocyclization and followed by aromatization
deliver quino[2,3-b]carbazoles (Scheme 1).
It is noteworthy that all N-protected QCs show intense fluores-
cence in liquid as well as in solid states. The photographs of QCs are
shown in Fig. 2. These compounds emit light in red region in solid
state and green region in liquid state (Fig. 5). It is observed that,
unprotected derivatives of QCs (3a, 3c, 3h and 3i) did fluoresce,
neither in solution nor in the solid state.
Fig. 2. Photographs of quinocarbazoles in solution state (CHCl3) and solid-state irra-
diated with UV light (365 nm).
Fluorescence behaviour is explained from the crystal packing.
We expected that fluorescence of unprotected QCs is quenched by
hydrogen bonding interaction between free eNH and carbonyl
oxygen. As we expected, strong inter and intramolecular hydrogen
2. Results and discussion
ꢀ
At the outset, we investigated the model reaction of N-methyl
indole with 2-(2-phenylethynyl)quinoline-3-carbaldehyde using
bonding are observed in 3a. The H(1)eO(1) distance is 2.202(2) A
ꢀ
(intermolecular), 2.458(2) A (intramolecular) (Fig. 3a). Such strong

K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
8271
Table 2
Heteroannulation of various indoles with quinoline alkynylaldehydea and optical properties of QCs
Entry
Substrate
Product
Yield (%)/time (h)
labs (nm)
lem (nm)
Liquid
Solid
Liquid
Solid
1b
2
R1¼H, R2¼Ph, R3¼H, R4¼H
3a
3b
3c
3d
3e
3f
3g
3h
3i
42/8
63/6
40/8
62/6
60/6
61/6
58/6
43/6
41/6
64/6
62/6
68/5
70/5
d
d
d
d
R1¼H, R2¼Ph, R3¼CH3, R4¼H
R1¼H, R2¼Ph, R3¼H, R4¼Br
384
d
355
d
530
d
626
d
3b
4
R1¼H, R2¼Ph, R3¼C2H5, R4¼H
R1¼H, R2¼Ph, R3¼C4H9, R4¼H
R1¼H, R2¼Ph, R3¼C6H13, R4¼H
R1¼H, R2¼Ph, R3¼Bn, R4¼H
R1¼H, R2¼p-tolyl, R3¼H, R4¼H
R1¼H, R2¼p-tolyl, R3¼H, R4¼Br
R1¼H, R2¼p-tolyl, R3¼CH3, R4¼H
R1¼H, R2¼p-tolyl, R3¼Bn, R4¼H
R1¼CH3, R2¼Ph, R3¼CH3 R4¼H
R1¼OCH3, R2¼Ph, R3¼CH3, R4¼H
382
384
384
383
d
358
324
333
313
d
531
518
531
519
d
600
630
590
611
d
5
6
7
8b
9b
10
11
12
13
d
d
d
d
3j
3k
3l
384
382
384
384
333
323
318
321
533
532
527
527
600
590
600
544
3m
a
Unless otherwise noted, all the reactions were carried out in DMA as a solvent at 120 ꢀC in presence of Cu(OTf)2 (5 mol %). Isolated yields.
No fluorescence was observed.
b
Scheme 1. Possible mechanism for the formation of quino[2,3-b]carbazoles.
intermolecular hydrogen bonding was not possible in N-protected
QCs. It is known that, emissive nature in the solid state of the
protected derivatives is more related to the lack of effective
p-
stacking rather than intermolecular hydrogen bonding.12 In crystal
structure for an unprotected derivative (3a), the molecules are ef-
fectively p-stacked along the crystallographic b axis. But, in crystal
structures 3e and 3l, only isolated pairs of p-stacked molecules can
be found.13
Surprisingly, fluorescent QCs showed significant quenching of
fluorescence in the presence of nitrobenzene; this interesting result
led us to an investigation on the efficiency of sensing for TNT. We
have thus extended our work on sensing of fluorescence using such
nitroaromatic explosives.
We studied TNT sensing and the results are given in Fig. 4.
Quenching of fluorescence was observed from other nitroaromatics
(2,6-dinitrotoluene,1,3-dinitrobenzene,1-chloro-2,4-dinitrobenzene,
ꢀ
Fig. 3. a. Perspective view of strong inter- (H(1)eO(1)¼2.202(2) A) and intramolecular
ꢀ
hydrogen bonding interaction ((H(1)eO(1)¼2.458(2) A)) in 3a. b. Centroid-to-centroid
13
ꢀ
distance (c1, c2, c3, c4, c5, c6 to c25, c26, c27, c28, c29¼3.737 A) in 3e is shown.
nitrobenzene) in 10
compound 3b in CH3CN. Upon addition of incremental amount of
10 M solution of TNT, fluorescence sensing was observed (Fig. 4).
mM level, while doing fluorescence titration of
m
Visual changes of colour is also observed (Fig. 6), when TNT is spotted
in quinocarbazole coated Whatman filter paper (See Supplementary
data, Page S7).
No sensing was observed with nitromethane. The fluorescence
intensity of 3b decreases linearly with increasing concentration of
nitroaromatic compounds. Visual sensing of nitrocompound also
observed. There is clear colour change while addition of DNT
(10 mM) in quinocarbazole (3b). After addition of nitrocompound,
fluorescent behaviour of QC was fully disappeared (Fig. 6).
We expect that there is an occurance of electron transfer between
3b and electron deficient nitroaromatics by formation of a
donoreacceptor (DeA) complex.
p-

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K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
160
140
120
100
80
0.30
0.25
0.20
0.15
0.10
0.05
0.00
3j
3k
3g
3e
3f
3d
3l
3m
60
40
20
300
400
500
600
0
Wavelength (nm)
500
550
600
650
700
Wavelength (nm)
45
40
35
30
25
20
15
10
5
Fig. 4. Emission spectral change (lex¼384 nm) of 3b with titration of 10
mM solution of
TNT in CH3CN (showing variation of emission intensity).
3j
3k
3g
3e
3f
3. Conclusion
3d
3l
3m
In summary, we have reported herein the synthesis of a family of
quino[2,3-b]carbazoles and the study of their photochemical be-
haviour in solution and in the solid state. These are very interesting
molecules, which have more stokes shift in solid phase than liquid
phase. Their fluorescent nature has been utilized for the sensing of
TNT. From the crystal packing, inter and intramolecular hydrogen
bonding for unprotected derivative (3a) were observed. It is note-
worthy that all compounds are linear, highly conjugated and have
binding sites. Moreover, the pyridine nitrogen, carbonyl oxygen and
free eNH are arranged in linear fashion. From this arrangement,
these molecules can find a new application in the field of chemical
biology as well as organic material. Further studies into the scope
and applications of this heteroannulation are currently pursued in
our laboratory and will be reported as events materialize.
0
450
500
550
600
650
700
750
Wavelength(nm)
4. Experimental section
4.1. General information
1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively, or at 500 and 125 MHz, respectively. Chemical shifts
were calculated in parts per million downfield from TMS (
d
¼0) for
1H NMR, and relative to the central CDCl3 resonance (
d
¼77.0) and
DMSO-d6
(
d
¼39.51) for 13C NMR. Data are presented as follows:
chemical shift, multiplicity (br¼broad signal, bs¼broad singlet,
s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet), cou-
pling constant in Hertz (Hz) and integration. HRMS (ESI) was
carried out at School of Chemistry, University of Hyderabad.
UVevis spectra were performed in a conventional quartz cell on
UVevis-NIR spectrophotometer (UV-3600). Fluorescence spectra
were recorded in a conventional quartz cell at 25 ꢀC on spectro-
fluorometer. X-ray diffraction measurements were carried out
40
35
30
25
20
15
10
5
3b
3j
3k
3e
3m
200
150
100
50
3k
3f
3d
at 298
monochromated Mo-K
ware or the X-ray intensity data were measured at 298 K on an
K
on an automated diffractometer using graphite-
0
0
ꢀ
a
(l¼0.71073 A) radiation with CAD4 soft-
450
500
550
600
650
700
750
800
450 500 550 600 650 700 750 800
Wavelength (nm)
Wavelength(nm)
instrument equipped with a graphite monochromator and a Mo-
Fig. 5. Absorption and emission spectra of quinocarbazoles. (a) Absorption spectra of
QCs in CH3CN. (b) Emission spectra of QCs in CH3CN. (c) Absorption spectra of QCs
(solid state). (d) Emission spectra of QCs (solid state).
ꢀ
K
a
fine-focus sealed tube (l¼0.71073 A). Melting points were
measured in open capillary tubes and are uncorrected. All the
obtained products were purified by column chromatography us-
ing silica gel (100e200 mesh). All reaction solvents used were of
GR grade and used without drying unless mentioned. All other
commercial reagents were used as received. Quinoline alkyny-
laldehydes were prepared according to methods already reported
in the literature.9b
4.2. General procedure for synthesis of quino[2,3-b]carbazoles
An oven-dried 10-mL round-bottomed flask equipped with
a Teflon-coated magnetic stirring bar was charged with 0.5 mmol

K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
8273
129.3, 129.2, 127.9, 127.6, 126.9, 125.0, 124.7, 124.3, 124.2, 121.8,
113.6, 112.5, 112.0 (Aromatic C); HRMS (ESI-MS) calcd for
C
26H15BrN2O; 451.0466 (MþH), found: 451.0464 (MþH), 453.0466
(Mþ2).
4.2.4. (7-Ethyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3d). Yield: 62%; Rf¼0.42 in 90% hexanes/10% EtOAc; mp
258e260 ꢀC; IR (KBr): 3742, 2958, 2915, 2860, 1660, 1594, 1468,
1101, 1019, 805 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 8.96 (s, 1H),
8.78 (s, 1H), 8.27 (d, J¼8.0 Hz, 1H), 7.93e8.00 (m, 4H), 7.53e7.63 (m,
3H), 7.40e7.44 (m, 3H), 7.32e7.36 (m, 2H), 4.21 (q, J¼7.0 Hz, 2H),
1.20 (t, J¼7.0 Hz, 3H); 13C NMR (125 MHz, TMS, CDCl3): 199.3, 148.6,
147.2, 144.1, 139.9, 139.4, 135.7, 133.1, 129.9, 129.6, 129.57, 128.6,
128.5, 127.9, 127.8, 124.8, 124.4, 122.5, 121.1, 121.0, 120.1, 119.2, 115.0,
108.7 (Aromatic C), 39.6,13.2 (Aliphatic C); HRMS (ESI-MS) calcd for
Fig. 6. Visual sensing of quino[2,3-b]carbazole (3b). a 10 mM solution of quino[2,3-b]
carbazole (3b). b 10 mM solution of quino[2,3-b]carbazole (3b)þ10 mM solution of 2,6-
dinitrotoluene (DNT).
C28H20N2O; 401.1654 (MþH), found: 401.1654.
4.2.5. (7-Butyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3e). Yield: 60%; Rf¼0.48 in 90% hexanes/10% EtOAc; mp
230e232 ꢀC; IR (KBr): 3739, 2988, 2900, 2880, 1657, 1590, 1448,
1090, 1030, 810 cmꢂ1; 1H NMR (400 MHz, TMS, CDCl3): 8.95 (s, 1H),
8.77 (s, 1H), 8.26 (d, J¼7.6 Hz, 1H), 7.93e7.99 (m, 4H), 7.53e7.64 (m,
3H), 7.39e7.43 (m, 3H), 7.30e7.34 (m, 2H), 4.10 (t, J¼8.0 Hz, 2H),
1.53 (br, 2H), 1.18 (sextet, J¼7.2 Hz, 2H), 0.74 (t, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, TMS, CDCl3): 199.1, 148.6, 147.2, 144.5, 140.1, 139.2,
135.7,133.1,130.0,129.6,128.6,128.5,127.9,124.7,124.4, 122.3,121.1,
121.0, 120.0, 119.1, 115.0, 108.8 (Aromatic C), 44.7, 30.5, 20.0, 13.6
(Aliphatic C); HRMS (ESI-MS) calcd for C30H24N2O; 429.1967
(MþH), found: 429.1967.
2-(2-phenylethynyl)quinoline-3-carbaldehyde (1a) 5 mol % of
Cu(OTf)2, and 5 mL DMA. To this 0.5 mmol of N-methyl indole (2a)
was added. Then the reaction mixture was stirred at 120 ꢀC until
the complete consumption of starting materials as monitored by
TLC. Then, solvent was removed under reduced pressure. The crude
reaction mixture was then poured over water and extracted with
EtOAc (3ꢁ20 mL). The organic layer was dried with anhydrous
Na2SO4 and the solvent was removed. The residue was purified by
column chromatography using silica gel with hexanes/ethyl acetate
mixture (eluent: 5% ethyl acetate in hexanes) to afford the product
3b; the product 3b was eluted as fluorescent solid. Yield: 63%. The
same procedure was followed for the synthesis of other quino[2,3-
b]carbazoles (3aem).
4.2.6. (7-Hexyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3f). Yield: 61%; Rf¼0.50 in 90% hexanes/10% EtOAc; mp
224e226 ꢀC; IR (KBr): 3749, 2955, 2900, 2850, 1647, 1490, 1448,
1110, 816 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 8.94 (s, 1H), 8.75
(s, 1H), 8.24 (d, J¼7.5 Hz, 1H), 7.90e7.98 (m, 4H), 7.50e7.61 (m, 3H),
7.36e7.42 (m, 3H), 7.29e7.31 (m, 2H), 4.07 (t, J¼8.5 Hz, 2H), 1.50 (br,
4.2.1. (7H-Indolo[3,2-b]acridin-6-yl)(phenyl)methanone (3a). Yield:
42%; Rf¼0.35 in 90% hexanes/10% EtOAc; mp 274e276 ꢀC; IR (KBr):
3395, 2955, 2910, 2850, 1655, 1594, 1468, 1400, 1250, 1100,
805 cmꢂ1 1H NMR (400 MHz, TMS, CDCl3): 10.21 (s, 1H), 8.98 (s,
;
2H), 1.09e1.17 (m, 4H), 1.01e1.05 (m, 2H), 0.80 (t, J¼7.5 Hz, 3H); 13
C
1H), 8.86 (s, 1H), 8.25 (d, J¼8.0 Hz, 1H), 8.02 (d, J¼8.4 Hz, 1H), 7.71
(m, 2H), 7.60e7.66 (m, 1H), 7.52e7.58 (m, 3H), 7.46e7.49 (m, 2H),
7.35e7.41 (m, 3H); 13C NMR (100 MHz, TMS, CDCl3): 198.8, 147.9,
146.4, 146.2, 142.9, 142.4, 136.7, 131.1, 130.2, 129.3, 129.2, 129.0,
128.1, 127.9, 127.5, 124.8, 124.7, 124.4, 122.3, 121.8, 121.4, 121.0, 111.6,
111.1 (Aromatic C); HRMS (ESI-MS) calcd for C26H16N2O; 373.1341
(MþH), found: 373.1341.
NMR (125 MHz, TMS, CDCl3): 199.0, 148.6, 147.3, 144.5, 140.1, 139.2,
135.7, 133.0, 130.0, 129.6, 129.55, 128.6, 128.5, 127.9, 127.8, 124.8,
124.4, 122.3, 121.0, 120.0, 119.1, 115.0, 108.8 (Aromatic C), 44.9, 31.3,
28.4, 26.3, 22.5, 14.0 (Aliphatic C); HRMS (ESI-MS) calcd for
C32H28N2O; 457.2280 (MþH), found: 457.2280.
4.2.7. (7-Benzyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3g). Yield: 58%; Rf¼0.48 in 90% hexanes/10% EtOAc; mp
252e254 ꢀC; IR (KBr): 2998, 2920, 2840, 1656, 1580, 1438, 1080,
1040, 800 cmꢂ1; 1H NMR (400 MHz, TMS, CDCl3): 8.97 (s, 1H), 8.83
(s, 1H), 8.31 (d, J¼7.2 Hz, 1H), 8.00 (d, J¼8.4 Hz, 1H), 7.86 (d,
J¼8.8 Hz, 1H), 7.60e7.64 (m, 3H), 7.53 (t, J¼7.6 Hz, 1H), 7.44 (t,
J¼7.2 Hz, 1H), 7.31e7.38 (m, 2H), 7.25 (s, 1H), 7.15 (t, J¼7.6 Hz, 2H),
6.96e6.97 (m, 3H), 6.79e6.81 (m, 2H), 5.48 (s, 2H); 13C NMR
(100 MHz, TMS, CDCl3): 198.9, 148.5, 147.3, 145.1, 140.4, 139.2,
136.4,135.7,132.4,129.7,129.6,128.8,128.3,128.0,127.8,127.1,126.1,
124.8, 124.5, 122.3, 121.2, 121.1, 120.5, 119.4, 115.8, 109.3 (Aromatic
C), 48.1 (Aliphatic C); HRMS (ESI-MS) calcd for C33H22N2O; 463.1810
(MþH), found: 463.1810.
4.2.2. (7-Methyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3b). Yield: 63%; Rf¼0.45 in 90% hexanes/10% EtOAc; mp
252e254 ꢀC; IR (KBr): 3400, 2945, 2890, 2750, 1559, 1500, 1400,
1250, 1128, 790 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 8.94 (s, 1H),
8.76 (s, 1H), 8.27 (d, J¼7.5 Hz, 1H), 7.97e8.00 (m, 3H), 7.92 (d,
J¼9.0 Hz, 1H), 7.54e7.67 (m, 3H), 7.43 (t, J¼8.0 Hz, 2H), 7.30e7.35
(m, 2H), 7.24e7.27 (m, 1H), 3.66 (s, 3H); 13C NMR (125 MHz, TMS,
CDCl3): 199.3, 148.6, 147.2, 145.0, 141.2, 140.0, 135.8, 133.0, 130.0,
129.6, 129.55, 128.8, 128.6, 128.5, 127.9, 127.6, 124.7, 124.4, 122.1,
121.1, 120.0, 119.3, 115.2, 108.4, (Aromatic C), 31.9 (Aliphatic C);
HRMS (ESI-MS) calcd for C27H18N2O; 387.1497 (MþH) found:
387.1497.
4.2.8. (7H-Indolo[3,2-b]acridin-6-yl)(p-tolyl)methanone (3h). Yield:
43%; Rf¼0.38 in 90% hexanes/10% EtOAc; mp 276e278 ꢀC; IR (KBr):
3023, 2998, 2920, 2890, 1647, 1690, 1548, 1160, 1032, 805 cmꢂ1; 1H
NMR (500 MHz, TMS, CDCl3): 10.10 (br s, 1H), 8.96 (s, 1H), 8.81 (s,
1H), 8.22 (d, J¼8.0 Hz, 1H), 8.02e8.03 (m, 4H), 7.66e7.67 (m, 1H),
7.54 (t, J¼7.0 Hz, 1H), 7.45e7.47 (m, 2H), 7.34 (t, J¼7.0 Hz, 1H), 7.18
(d, J¼8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, TMS, CDCl3):
198.3,148.0,146.3,145.7,144.4,143.1,142.1,138.9,136.6,130.3,130.1,
129.8, 129.2, 128.9, 128.3, 127.9, 124.7, 123.7, 122.3, 121.8, 121.4,
4.2.3. (10-Bromo-7H-indolo[3,2-b]acridin-6-yl)(phenyl)methanone
(3c). Yield: 40%; Rf¼0.35 in 90% hexanes/10% EtOAc; mp
262e264 ꢀC; IR (KBr): 3380, 2955, 2870, 2690, 1555, 1490, 1256,
790 cmꢂ1 1H NMR (500 MHz, TMS, CDCl3): 10.16 (s, 1H), 8.98 (s,
;
1H), 8.82 (s, 1H), 8.36 (s, 1H), 8.03 (d, J¼8.5 Hz, 1H), 7.72 (d,
J¼8.0 Hz, 2H), 7.66 (t, J¼6.5 Hz, 2H), 7.53e7.58 (m, 2H), 7.49 (t,
J¼7.5 Hz, 1H), 7.35e7.40 (m, 3H); 13C NMR (125 MHz, TMS, CDCl3):
198.7, 148.2, 146.3, 145.9, 142.0, 141.6, 136.9, 131.6, 131.3, 130.5,

8274
K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
120.8, 112.2, 111.1 (Aromatic C), 21.7 (Aliphatic C); HRMS (ESI-MS)
55.4, 31.8 (Aliphatic C); HRMS (ESI-MS) calcd for C28H20N2O2;
calcd for C27H18N2O; 387.1497 (MþH), found: 387.1497.
417.1603 (MþH), found: 417.1603.
4.2.9. (10-Bromo-7H-indolo[3,2-b]acridin-6-yl)(p-tolyl)methanone
(3i). Yield: 41%; Rf¼0.36 in 90% hexanes/10% EtOAc; mp
282e284 ꢀC; IR (KBr): 3740, 3005, 2950, 2850, 1627, 1490, 1348,
1080, 1035, 820 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 9.93 (s, 1H),
8.99 (s, 1H), 8.81 (s, 1H), 8.35 (s, 1H), 8.04 (d, J¼8.5 Hz, 1H),
7.65e7.68 (m, 5H), 7.48e7.51 (m, 1H), 7.33 (d, J¼8.0 Hz, 1H), 7.18 (d,
J¼8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (125 MHz, TMS, CDCl3): 198.1,
148.3, 146.3, 145.4, 142.4, 141.6, 138.7, 136.9, 131.5, 130.5, 130.2,
129.9, 129.2, 128.4, 128.0, 126.8, 125.0, 124.8, 124.3, 124.2, 121.8,
113.4, 112.7, 112.4 (Aromatic C), 21.7 (aliphatic C); HRMS (ESI-MS)
calcd for C27H17BrN2O; 465.0602 (MþH), found: 465.0602 (MþH),
467.0585 (Mþ2).
Acknowledgements
We thank DST (Project number: SR/S1/OC-70/2008) for financial
assistance and for the single-crystal X-ray diffractometer facility in
our school. We thank Advanced Centre for Research in High Energy
Materials, University of Hyderabad for providing TNT and specifi-
cally Dr. Pradeepta K. Panda. K.S.P. thanks UGC, INDIA for a Senior
Research Fellowship.
Supplementary data
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2013.07.016.
4.2.10. (7-Methyl-7H-indolo[3,2-b]acridin-6-yl)(p-tolyl)methanone
(3j). Yield: 64%; Rf¼0.48 in 90% hexanes/10% EtOAc; mp
258e260 ꢀC; IR (KBr): 3739, 2958, 2905, 2860, 1657, 1540, 1468,
1060, 1020, 810 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 8.89 (s, 1H),
8.71 (s, 1H), 8.21 (d, J¼7.5 Hz, 1H), 7.92 (m, 2H), 7.83 (d, J¼8.0 Hz,
2H), 7.53e7.57 (m, 2H), 7.38 (t, J¼8.0 Hz, 1H), 7.24e7.30 (m, 2H),
7.18 (d, J¼8.0 Hz, 2H), 3.62 (s, 3H), 2.37 (s, 3H); 13C NMR (125 MHz,
TMS, CDCl3): 198.9, 148.6, 147.1, 145.0, 143.9, 141.0, 137.6, 135.8,
130.1, 129.6, 129.5, 129.3, 128.6, 127.9, 127.6, 124.8, 124.4, 122.1,
121.2, 121.1, 120.0, 119.2, 115.5, 108.4 (Aromatic C), 31.8, 21.7 (Ali-
phatic C); HRMS (ESI-MS) calcd for C28H20N2O; 401.1654 (MþH),
found: 401.1654.
References and notes
€
1. (a) Schmidt, A. W.; Reddy, K. R.; Knolker, H.-J. Chem. Rev. 2012, 112, 3193e3328;
€
(b) Knolker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303e4427; (c) Li, J.;
€
Grimsdale, A. C. Chem. Soc. Rev. 2010, 39, 2399e2410; (d) Knolker, H.-J. In The
Alkaloids; Cordell, G. A., Ed.; Academic: Amsterdam, 2008; Vol. 65, pp 1e430.
2. (a) Pagano, N.; Wong, E. Y.; Breiding, T.; Liu, H.; Wilbuer, A.; Bregman, H.; Shen,
Q.; Diamond, S. L.; Meggers, E. J. Org. Chem. 2009, 74, 8997e9009; (b) Bregman,
H.; Williams, D. S.; Atilla, G. E.; Carroll, P. J.; Meggers, E. J. Am. Chem. Soc. 2004,
126, 13594e13595; (c) Williams, D. S.; Atilla, G. E.; Bregman, H.; Arzoumanian,
A.; Klein, P. S.; Meggers, E. Angew. Chem., Int. Ed. 2005, 44, 1984e1987; (d)
Bregman, H.; Carroll, P. J.; Meggers, E. J. Am. Chem. Soc. 2006, 128, 877e884; (e)
Bregman, H.; Meggers, E. Org. Lett. 2006, 8, 5465e5468; (f) Debreczeni, J.-E.;
Bullock, A. N.; Atilla, G. E.; Williams, D. S.; Bregman, H.; Knapp, S.; Meggers, E.
Angew. Chem., Int. Ed. 2006, 45, 1580e1585; (g) Maksimoska, J.; Feng, L.; Harms,
K.; Yi, C.; Kissil, J.; Marmorstein, R.; Meggers, E. J. Am. Chem. Soc. 2008, 130,
15764e15765; (h) Dieckmann, S.; Riedel, R.; Harms, K.; Meggers, E. Eur. J. Inorg.
Chem. 2012, 813e821.
3. (a) Palayangoda, S. S.; Cai, X.; Adhikari, R. M.; Neckers, D. C. Org. Lett. 2008, 10,
281e284; (b) Wu, Y.; Li, Y.; Gardner, S.; Ong, B. S. J. Am. Chem. Soc. 2005, 127,
614e618; (c) Hu, N.-X.; Xie, S.; Popovic, Z.; Ong, B.; Hor, A.-M. J. Am. Chem. Soc.
1999, 121, 5097e5098; (d) Kawaguchi, K.; Nakano, K.; Nozaki, K. Org. Lett. 2008,
10, 1199e1202; (e) Wong, K.-T.; Chen, Y.-M.; Lin, Y.-T.; Su, H.-C.; Wu, C.-C. Org.
Lett. 2005, 7, 5361e5364; (f) Zhang, S.; Chen, R.; Yin, J.; Liu, F.; Jiang, H.; Shi, N.;
An, Z.; Ma, C.; Liu, B.; Huang, W. Org. Lett. 2010, 12, 3438e3441.
4. For recent selected reports, see: (a) Boens, N.; Leen, V.; Dehaen, W. Chem. Soc.
Rev. 2012, 41, 1130e1172; (b) Han, J.; Burgess, K. Chem. Rev. 2010, 110,
2709e2728; (c) Kundu, K.; Knight, S. F.; Willett, N.; Lee, S.; Taylor, W. R.;
Murthy, N. Angew. Chem., Int. Ed. 2009, 48, 299e303; (d) Quang, D. T.; Kim, J. S.
Chem. Rev. 2010, 110, 6280e6301; (e) You, Y.; Han, Y.; Lee, Y.-M.; Park, S. Y.;
Nam, W.; Lippard, S. J. J. Am. Chem. Soc. 2011, 133, 11488e11491; (f) Buccella, D.;
Horowitz, J. A.; Lippard, S. J. J. Am. Chem. Soc. 2011, 133, 4101e4114; (g) Ajaya-
ghosh, A.; Carol, P.; Sreejith, S. J. Am. Chem. Soc. 2005, 127, 14962e14963; (h)
Kim, T.-H.; Swager, T. M. Angew. Chem., Int. Ed. 2003, 42, 4803e4806; (i) Kwan,
P. H.; MacLachlan, M. J.; Swager, T. M. J. Am. Chem. Soc. 2004, 126, 8638e8639;
(j) Zhou, Q.; Swager, T. M. J. Am. Chem. Soc. 1995, 117, 7017e7018; (k) Ajaya-
ghosh, A.; Arunkumar, E.; Daub, J. Angew. Chem., Int. Ed. 2002, 41, 1766e1769.
5. Pluth, M. D.; McQuade, L. E.; Lippard, S. J. Org. Lett. 2010, 12, 2318e2321.
6. Belousov, V. V.; Fradkov, A. F.; Lukyanov, K. A.; Staroverov, D. B.; Shakhbazov, K.
S.; Terskikh, A. V.; Lukyanov, S. Nat. Methods 2006, 3, 281e286.
4.2.11. (7-Benzyl-7H-indolo[3,2-b]acridin-6-yl)(p-tolyl)methanone
(3k). Yield: 62%; Rf¼0.45 in 90% hexanes/10% EtOAc; mp
262e264 ꢀC; IR (KBr): 3735, 2991, 2900, 2480, 1647, 1690, 1458,
1090, 1030, 816 cmꢂ1; 1H NMR (400 MHz, TMS, CDCl3): 8.87 (s, 1H),
8.74 (s, 1H), 8.24 (d, J¼6.8 Hz, 1H), 7.90 (d, J¼8.0 Hz, 1H), 7.85 (d,
J¼8.8 Hz, 1H), 7.50e7.52 (m, 2H), 7.30e7.37 (m, 4H), 7.16 (d,
J¼7.6 Hz, 1H), 6.87e6.94 (m, 5H), 6.79 (m, 2H), 5.40 (s, 2H), 2.24 (s,
3H); 13C NMR (100 MHz, TMS, CDCl3): 198.6, 148.6, 147.2, 145.0,
143.3, 140.3, 136.7, 136.6, 135.7, 129.9, 129.7, 129.6, 128.8, 128.76,
128.3, 127.9, 127.8, 126.8, 126.1, 124.8, 124.5, 122.3, 121.2, 121.1,
120.4, 119.2, 116.1, 109.3 (Aromatic C), 48.1, 21.6 (Aliphatic C);
HRMS (ESI-MS) calcd for C34H24N2O; 477.1967 (MþH) found:
477.1967.
4.2.12. (2,7-Dimethyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)meth-
anone (3l). Yield: 68%; Rf¼0.42 in 90% hexanes/10% EtOAc; mp
290e292 ꢀC; IR (KBr): 3759, 2968, 2940, 2870, 1647, 1590, 1448,
1130 cmꢂ1 1H NMR (500 MHz, TMS, CDCl3): 8.77 (s, 1H), 8.69 (s,
;
1H), 8.24 (d, J¼7.5 Hz, 1H), 7.97e7.99 (m, 2H), 7.82 (d, J¼9.0 Hz, 1H),
7.67 (s, 1H), 7.53e7.58 (m, 2H), 7.43 (m, 3H), 7.31 (t, J¼7.0 Hz, 1H),
7.27e7.30 (m, 1H), 3.64 (s, 3H), 2.52 (s, 3H); 13C NMR (125 MHz,
TMS, CDCl3): 199.4, 147.5, 146.6, 144.9, 140.8, 139.9, 139.3, 134.6,
134.0, 132.9, 132.5, 129.9, 129.1, 128.5, 127.3, 125.8, 122.1, 121.2,
121.0, 119.9, 115.1, 114.1, 108.3 (Aromatic C), 31.8, 21.7 (Aliphatic C);
HRMS (ESI-MS) calcd for C28H20N2O; 401.1654 (MþH), found:
401.1654.
7. (a) Bhalla, V.; Gupta, A.; Kumar, M. Org. Lett. 2012, 14, 3112e3115; (b) Sohn, H.;
Calhoun, R. M.; Sailor, M. J.; Trogler, W. C. Angew. Chem., Int. Ed. 2001, 40,
2104e2105; (c) Lee, Y. H.; Liu, H.; Lee, J. Y.; Kim, S. H.; Kim, S. K.; Sessler, J. L.;
Kim, Y.; Kim, J. S. Chem.dEur. J. 2010, 16, 5895e5901; (d) Toal, S. J.; Magde, D.;
Trogler, W. C. Chem. Commun. 2005, 5465e5467; (e) Sohn, H.; Sailor, M. J.;
Magde, D.; Trogler, W. C. J. Am. Chem. Soc. 2003, 125, 3821e3830; (f) Andrew, T.
L.; Swager, T. M. J. Am. Chem. Soc. 2007, 129, 7254e7255; (g) Kartha, K. K.; Babu,
S. S.; Srinivasan, S.; Ajayaghosh, A. J. Am. Chem. Soc. 2012, 134, 4834e4841; (h)
Yang, J.-S.; Swager, T. M. J. Am. Chem. Soc. 1998, 120, 11864e11873; (i) Yang, J.-S.;
Swager, T. M. J. Am. Chem. Soc. 1998, 120, 5321e5322; (j) Zhang, C.; Che, Y.; Yang,
X.; Bunes, B. R.; Zang, L. Chem. Commun. 2010, 5560e5562; (k) Feng, L.; Li, H.;
4.2.13. (2-Methoxy-7-methyl-7H-indolo[3,2-b]acridin-6-yl)(phenyl)
methanone (3m). Yield: 70%; Rf¼0.48 in 90% hexanes/10% EtOAc;
mp 302e304 ꢀC; IR (KBr): 3012, 2950, 2980, 1647, 1595, 1458, 1110,
1080, 900 cmꢂ1; 1H NMR (500 MHz, TMS, CDCl3): 8.61 (s, 1H), 8.59
(s, 1H), 8.23 (d, J¼8.0 Hz, 1H), 7.98 (d, J¼7.5 Hz, 2H), 7.80 (d,
J¼9.5 Hz, 1H), 7.55 (t, J¼7.5 Hz, 2H), 7.41 (t, J¼7.5 Hz, 2H), 7.29e7.30
(m, 2H), 7.22 (d, J¼8.0 Hz, 1H), 7.02 (s, 1H), 3.92 (s, 3H), 3.60 (s, 3H);
13C NMR (125 MHz, TMS, CDCl3): 199.5, 156.1, 145.7, 145.6, 144.9,
140.3, 139.9, 133.4, 133.0, 131.0, 129.9, 128.5, 128.4, 127.3, 125.3,
124.8,122.0,121.3,121.1,119.7,118.7,115.2,108.3,102.7 (Aromatic C),
€
Qu, Y.; Lu, C. Chem. Commun. 2012, 4633e4635; (l) Venkatramaiah, N.; Kumar,
S.; Patil, S. Chem. Commun. 2012, 5007e5009; (m) Mathew, A.; Sajanlal, P. R.;
Pradeep, T. Angew. Chem., Int. Ed. 2012, 51, 9596e9600 For a review on reagents
to detect explosives, see: (n) Salinas, Y.; Manez, R. M.; Marcos, M. D.; Sancenon,
F.; Costero, A. M.; Parraad, M.; Gilad, S. Chem. Soc. Rev. 2012, 41, 1261e1296; (o)
Rana, A.; Panda, P. K. RSC Adv. 2012, 2, 12164e12168.
ꢁꢂ
ꢁ
8. Prasanna de Silva, A. Nat. Chem. 2012, 4, 440e441.
9. (a) Godoi, B.; Schumacher, R. F.; Zeni, G. Chem. Rev. 2011, 111, 2937e2980; (b)
Verma, A. K.; Rustagi, V.; Aggarwal, T.; Singh, A. P. J. Org. Chem. 2010, 75,
7691e7703; (c) Roesch, K. R.; Larock, R. C. Org. Lett. 1999, 1, 553e556; (d)
Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86e94; (e) Dai, G.; Larock, R. C.
Org. Lett. 2001, 3, 4035e4038; (f) Asao, N.; Takahashi, K.; Lee, S.; Kasahara, T.;

K.S. Prakash, R. Nagarajan / Tetrahedron 69 (2013) 8269e8275
8275
Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650e12651; (g) Dai, G.; Larock, R. C.
Org. Lett. 2002, 4, 193e196; (h) Asao, N.; Kasahara, T.; Yamamoto, Y. Angew.
Chem. 2003, 115, 3628e3630; Angew. Chem., Int. Ed. 2003, 42, 3504e3506; (i)
Huang, Q.; Hunter, J. A.; Larock, R. C. Org. Lett. 2001, 3, 2973e2976; (j) Bera, K.;
Sarkar, S.; Biswas, S.; Maiti, S.; Jana, U. J. Org. Chem. 2011, 76, 3539e3544; (k)
Chaitanya, T. K.; Nagarajan, R. Org. Biomol. Chem. 2011, 9, 4662e4670; (l) Pra-
kash, K. S.; Nagarajan, R. Tetrahedron Lett. 2013, 54, 3635e3638. For a review on
benzannulation, see: (m) Kotha, S.; Misra, S.; Halder, S. Tetrahedron 2008, 64,
10775e10790.
C
30H24N2O1, unit cell parameters: a¼12.0524(17), b¼13.4942(19), c¼15.342(2);
space group Pꢂ1. The CCDC deposition number of 3l is 900314; molecular
formula: C28H20N2O1, unit cell parameters: a¼33.695(3), b¼30.274(2), c¼8.
2167(7); space group Fdd2.
11. (a) Dyker, G.; Hildebrandt, D.; Liu, J.; Merz, K. Angew. Chem. 2003, 115,
4536e4538; Angew. Chem., Int. Ed. 2003, 42, 4399e4402; (b) Tang, R. Y.; Li, J. H.
Chem.dEur. J. 2010, 16, 4733e4738; (c) Prakash, K. S.; Nagarajan, R. Adv. Synth.
Catal. 2012, 354, 1566e1578.
€
12. Langhals, H.; Potrawa, T.; Noth, H.; Linti, G. Angew. Chem., Int. Ed. Engl. 1989, 28,
10. The CCDC deposition number of 3a is 900312; molecular formula: C26H16N2O1,
unit cell parameters: a¼17.4997(15), b¼4.9148(4), c¼21.8498(16); space group
P21/n. The CCDC deposition number of 3e is 900313; molecular formula:
478e480.
13. The detailed crystal packing of 3a, 3e and 3l. (See Supplementary data, pages
S2eS4).