Expeditious synthetic approach and photophysical properties of fluorescent benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine derivatives

Article abstract of DOI:10.1039/c2ra22527a

A short and efficient synthetic route to novel benzimidazo[1,2-d]dibenzo[b, f][1,4]diazepines has been developed using a copper catalyzed intramolecular Ullmann type C-N bond forming reaction as a key step. Copper iodide and 1,10-phenanthroline furnished the desired compounds in good yield. The products are intensely fluorescent with appreciably long lifetimes. Looking at their prospective use as markers for biomacromolecules and in biochemical analysis, we have explored the photophysical properties of these compounds. The spectrophotometric and spectrofluorometric studies reveal that while the absorbance maxima of the compounds are in the UV region, the emission maxima fall in the visible (blue-green) region.

Full text of DOI:10.1039/c2ra22527a

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PAPER
Expeditious synthetic approach and photophysical
properties of fluorescent benzimidazo[1,2-
d]dibenzo[b,f][1,4]diazepine derivatives3
Cite this: RSC Advances, 2013, 3,
1862
Sudipta Mitra,a Nitin Chattopadhyayb and Partha Chattopadhyay*a
A short and efficient synthetic route to novel benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepines has been
developed using a copper catalyzed intramolecular Ullmann type C–N bond forming reaction as a key step.
Copper iodide and 1,10-phenanthroline furnished the desired compounds in good yield. The products are
intensely fluorescent with appreciably long lifetimes. Looking at their prospective use as markers for
biomacromolecules and in biochemical analysis, we have explored the photophysical properties of these
compounds. The spectrophotometric and spectrofluorometric studies reveal that while the absorbance
maxima of the compounds are in the UV region, the emission maxima fall in the visible (blue-green)
region.
Received 16th October 2012,
Accepted 22nd November 2012
DOI: 10.1039/c2ra22527a
www.rsc.org/advances
catalyst and phosphine ligands.13–21
A blemish in this
Introduction
amination reaction is that these ligands are often air-sensitive,
toxic, and expensive. Consequently, the copper-based proto-
cols of Ullmann type amination attracted our attention in view
of its low cost and low toxicity. We therefore became interested
in taking up a project on the synthesis of this new class of
compounds, benzimidazole fused dibenzodiazepines exploit-
ing copper chemistry. We herein report our results on Cu
catalyzed intramolecular cycloamination reaction,22–26 leading
to the formation of benzimidazodibenzodiazepines.
The synthesized compounds are fluorescent with appreci-
ably long lifetimes. So they are promising agents to be tagged
with biomacromolecules like DNA, RNA etc. to serve as
markers for biochemical analysis. Fluorescence has been a
major topic for photofunctional materials, and has found
extensive applications in a variety of fields such as organic
light emitting diodes (OLED), photovoltaic cells, laser chem-
istry, fluorescent probes and related areas.27 Organic electro-
luminescent devices employing organic fluorophore emitters
have been the focus of considerable interest because of their
possible applications as displays for mobile phones, personal
computers, and televisions.28–33 The strong fluorescence of
some of our synthesized compounds leads to the optimism
that they may also be used as promising emitters for the
fabrication of electroluminescent devices covering a wide
range of color. Considering the prospects in this area, we have
studied the photophysical properties of the synthesized
compounds in some detail.
Over the past few years, interest has been growing in the
synthesis of various benzimidazole fused medium ring
heterocycles due to the pharmacological, medicinal and
biological activities associated with hybrid structures involving
benzimidazole1–4 and medium rings.5,6 Among them, benzi-
midazo benzodiazepines play an important role in pharma-
ceuticals.7–11
For
example
tetrahydroimidazo[4,5,1-
jk][l,4]benzodiazepi-2(1H)-thione (TIBO),10,11 the first member
of a series of potent selective, non-competitive inhibitors of
HIV-l reverse transcriptase and Tivirapine (8-chloro TIBO), a
preclinical lead belong to the class of benzimidazobenzodia-
zepines while UK-129 485 is an imidazobenzodiazepine.7–9
A
search in the literature revealed that there are only few reports
on the synthesis of benzimidazoles fused with benzazepine
and benzodiazepine.12 These include ring-closing metathesis,
metal induced C–C bond formation, microwave irradiation or
other methods. However the synthesis of dibenzofused
benzimidazobenzodiazepine ring has not been reported so
far. For quite sometime, we have been engaged in the
synthesis of several benzannulated and dibenzannulated
medium ring heterocycles by means of the most effective
alternative, Buchwald–Hartwig intramolecular C–N/C–O bond
forming cyclization reaction in the presence of Pd based
aChemistry Division, CSIR Indian Institute of Chemical Biology, 4 Raja S.C. Mullick
Road, Kolkata, 700 032, India. E-mail: partha@iicb.res.in; Fax: +91 33 2473 5197;
Tel: +91-33-2473 0492
bDepartment of Chemistry, Jadavpur University, Kolkata, 700 032, India
Electronic supplementary information (ESI) available: Copies of 1H NMR and
3
13C NMR spectra for all the synthesized compounds and COSY, NOSY spectra of
4e. See DOI: 10.1039/c2ra22527a
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Scheme 1 Synthesis of benzimidazole fused aromatic amines. Reagents and conditions: (a) acetone, KOH, o-fluoronitrobenzenes, reflux, 5 h. (b) Fe, AcOH, 80 uC, 1 h.
structures. For example, the 1H NMR of 3a consisted of one
exchangeable sharp singlet for amine (–NH2) protons (d = 3.67)
along with appropriate chemical shifts for the twelve aromatic
protons of the three aromatic moieties.
Results and discussion
The starting materials 1a–e were synthesized34 by heating a
mixture of commercially available o-phenylenediamines and
o-bromobenzoic acids with polyphosphoric acid (PPA) in neat
The amine precursor 3a was chosen as a representative
conditions. These products were then refluxed in dry acetone
substrate for the optimization studies of intramolecular
for 4–5 h in presence of o-fluoronitrobenzenes and KOH to
give the intermediates 2a–h (Scheme 1) in good yield.
However, 2d and 2f were isolated as regioisomeric mixtures.
When we used 1e, the reaction was somewhat more complex
and the separation was difficult. So we subjected the mixture
directly to the next step. All the N-arylated benzimidazoles
cycloamination reaction using copper source, ligands, solvents
and bases (Table 1). In order to optimize this coupling
protocol, the influence of each parameter on the outcome of
the reaction was thoroughly investigated. As shown in Table 1,
various copper salts including CuI, CuCl, Cu(OAc)2?H2O, and
CuSO4?5H2O were studied as alternative catalyst precursors.
were reduced in presence of iron and acetic acid to afford the
Although all these copper compounds are catalytically active,
amines 3a–h in good to excellent yield (Scheme 1). The spectral
data of 3a–h are in full agreement with the assigned
none of them is as effective as CuI (Entry 6, Table 1). The best
result was obtained with 5 mol% catalyst loading. Ligands
Table 1 Optimization of copper catalysts, ligands, solvents and bases on the cyclization of amine precursor 3a to benzimidazodibenzdiazepine 4a
Entry
Catalyst (5 mol%)
Ligand (10 mol%)
Base (2 equiv.)
Solvent (8 mL)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuSO4?5H2O
Cu(OAc)2?H2O
CuCl
—
—
L1
K2CO3
KO-tBu
K2CO3
KO-tBu
K2CO3
KO-tBu
KO-tBu
KO-tBu
KO-tBu
KO-tBu
KO-tBu
KO-tBu
KO-tBu
KO-tBu
DMF
DMF
DMF
DMF
Toluene
Toluene
Toluene
Toluene
DME
17 h
17 h
17 h
18 h
18 h
17 h
17 h
17 h
16 h
17 h
18 h
18 h
18 h
18 h
2
5
b
30
45
52
72
52
47
35
25
42
12
18
22
L1
L1
L1c
L2d
L3
L1
L1
L1
L1
L1
L1
THF
1,4-Dioxane
Toluene
Toluene
Toluene
a
b
c
d
Isolated Yield. L1: 1,10 phenanthroline monohydrate. L2: (¡)-trans-1,2-cyclohexane diamine. L3: N,N9-dimethylethylene diamine.
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including 1,10-phenanthroline monohydrate (L1), (¡)-trans-
1,2-cyclohexane
diamine
(L2)
and
N,N9-dimethylethylenediamine (L3) were screened, with L2
and L3 proving less efficient than L1. Bases were found to have
dramatic influence on the cyclization reaction and KO-tBu (2
equiv.) was the most effective one. A study of the solvent effect
(THF, DMF, DME, 1,4-dioxane and toluene) suggested that
toluene was the solvent of choice. The optimal temperature for
the coupling proved to be 110–120 uC (higher temperatures
gave the same results) and the reaction was complete within 17
h, as revealed by the consumption of the aryl bromide by TLC.
The optimized conditions for the aryl amination reaction of 3a
employed CuI (5 mol%) as a catalyst, 1,10-phenanthroline
monohydrate (10 mol%) as a ligand, KO-tBu (2 equiv.) as a
base, and toluene as solvent. To the best of our knowledge,
this is the first copper catalyzed intramolecular aryl amination
reaction using benzimidazole fused aromatic primary amines.
With 3d and 3f the products (4d and 4f, Fig. 1) were isolated
as difficult to separate regioisomeric mixtures (4d and 4d*;4f
and 4f*, Fig. 1). Interestingly, 3e furnished a single isomer 4e
(Fig. 1). The structure of 4e could be predicted using COSY and
NOESY spectral analysis. The singlet at d 8.13 can only belong
to the proton lying between the imidazole ring and the benzoyl
group. As it showed NOESY correlation with the proton signal
at d 7.76 (doublet), assignable to H-9 of the neighbouring
benzene ring, only the isomer 4e (Fig. 1) appeared likely.
We have made spectrophotometric and fluorometric
studies of the synthesized compounds 4a–h in dichloro-
methane medium. The normalized absorption and fluores-
cence spectra are depicted in Fig. 2 and 3 respectively to reveal
the spectral shifts for the different molecular systems. For the
absorption measurements, concentrations of all the com-
Fig. 2 Normalized absorption spectra of 4a–h in dichloromethane (normalized
at 290 nm).
compounds do not differ very much from one another except
4e for which both the absorption and the fluorescence spectra
show remarkable bathochromic shifts.
The fluorescence maxima are reported in Table 2. A
remarkable bathochromic shift in the emission spectrum of
4e compared to the others is worth mentioning. This may be
ascribed to an extension of conjugation of the p electrons from
the benzimidazole ring to the benzoyl (–COPh) group. The
fluorescence quantum yields (Wf) of the products, measured
using quinine sulphate in 1.0 N sulfuric acid solution as a
standard (Wf # 0.54),35 were found to vary widely in the range
0.02–0.22 (Table 2). A critical look at selected pairs of
compounds differing in one methyl substitution (4a-4b, 4a-
pounds in the experimental solution were y1026 mol dm23
As is obvious from the figures the spectral behavior of the
.
Fig. 1 List of products formed by intramolecular aryl amination of aryl bromides with CuI. Reaction conditions: CuI (5 mol%), 1,10 phenanthroline?H2O (10 mol%), KO-
tBu (2 equiv.), toluene, 110 uC, 17–19 h.
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Fig. 4 Fluorescence decays of the synthesized compounds in dichloromethane.
The samples are indicated in the legends. The sharp profile in black represents
the instrumental response function (IRF).
Fig. 3 Normalized fluorescence spectra of 4a–h in dichloromethane. lexc = 358
nm.
and non-radiative (knr) decay constants for all the compounds
were determined from the fluorescence quantum yields (Wf)
and lifetimes (t) using the following relations. The values are
displayed in Table 3.
4g, 4a-4d, 4g-4f, 4c-4h) reveals that introduction of the methyl
group leads to an increase in the fluorescence quantum yield;
although the increment in the Wf value depends on the
particular point of attachment of the group. Similarly, a
comparison with 4a-4c and 4g-4h reveals that introduction of a
wf
kr~
(1)
(2)
–CF3 group induces
a remarkable enhancement in the
tf
fluorescence quantum yield, although we cannot offer any
specific reason for this increase at this moment. The high
fluorescence quantum yields of some of the compounds,
particularly 4h, render them useful as fluorescence standards
as well as markers of the biological samples like DNA.
1
krzknr~
tf
The fluorescence lifetimes of the compounds were deter-
mined from time-resolved intensity decays by the method of
time-correlated single-photon counting (TCSPC). All the
samples were excited at 370 nm. The monitoring wavelength
was 500 nm for all the samples except 4e for which it was 535
nm. The fluorescence decays of all the compounds were single
exponentials (Fig. 4). The lifetimes (t) of the excited species
were extracted through deconvolution and the values are
presented in Table 3. Interestingly, all these compounds
exhibit relatively long fluorescence lifetimes. The radiative (kr)
Both high fluorescence quantum yield and long lifetime
should render some of these novel compounds efficient
fluorescent markers for biosystems to be studied in vivo using
single molecule fluorescence techniques. The positive fluoro-
metric behavior may also be exploited towards developing
electroluminescent display devices.
Table 2 Steady state photophysical parameters of compounds 4a–h
Table 3 Dynamic photophysical parameters of compounds 4a–h
tf (ns)a
kr (s21) (Wf/tf)b
knr (s21 c
)
a
b
Compound
lexc (nm)
lem (nm)
Wfc
Compound
Wf
4a
4b
4c
4d
4e
4f
291
293
292
293
309
293
288
292
499
510
502
510
533
497
498
499
0.045
0.058
0.122
0.080
0.025
0.138
0.133
0.219
4a
4b
4c
4d
4e
4f
0.045
0.058
0.122
0.080
0.025
0.138
0.133
0.219
8.60
5.59
18.56
9.50
5.23 6 106
10.38 6 106
6.57 6 106
8.42 6 106
7.96 6 106
11.22 6 106
11.10 6 106
9.71 6 106
11.11 6 107
16.85 6 107
4.73 6 107
9.68 6 107
31.05 6 107
7.01 6 107
7.24 6 107
3.46 6 107
3.14
12.30
11.98
22.56
4g
4h
4g
4h
a
b
c
a
b
c
Excitation wavelength. Emission wavelength. Fluorescence
quantum Yield.
Fluorescence lifetime. Radiative decay constant. Non-radiative
decay constant.
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yellow solid 2a (0.221 g, 76%) ; mp 155–157 uC, IR (KBr, nmax
)
Conclusions
3062, 1602, 1530, 1442, 1381, 1345, 1320, 1260, 1192, 1123,
1025, 849, 761, 748, 700, 620 cm21; EtOAc : Pet.ether (3 : 7); Rf
0.47. 1H NMR (300 MHz, CDCl3) d 7.14 (d, J = 7.8 Hz, 1H), 7.22–
7.33 (m, 3H), 7.35–7.40 (m, 1H), 7.42–7.46 (m, 1H), 7.52–7.56
(m, 1H), 7.59–7.61 (m, 1H), 7.65–7.75 (m, 2H), 7.94 (d, J = 8.1
Hz, 1H), 8.00 (dd, J = 8.1, 1.2 Hz, 1H). 13C NMR (75 MHz,
CDCl3) d 109.6, 120.6, 123.3, 123.4, 124.1, 125.7, 127.4, 129.4,
130.0, 131.0, 131.2, 131.5, 132.5, 132.7, 134.0, 135.6, 142.9,
145.8, 151.1. ESI-MS m/z : 394, 396 (M+H+ for 79Br, 81Br), 416,
418 (M+Na+ for 79Br, 81Br). Anal. Calcd C19H12BrN3O2; C, 57.89;
H, 3.07; N, 10.66; found C, 58.09; H, 3.02; N, 10.81.
In summary, we have developed a simple and efficient three-
step synthetic route to benzimidazole fused dibenzodiazepines
using a copper catalyzed intramolecular Ullmann type amina-
tion reaction as the key step. The presence of –NH group in the
diazepine unit offers more opportunities for further functio-
nalization. The photophysical studies reveal that some of these
compounds are novel fluorophores having high fluorescence
quantum yields and long lifetime. Apart from the pharmaceu-
tical prospect of the synthesized compounds, the fluorometric
properties are expected to make them promising for their use
as biomarkers in cells.
2-(2-Bromophenyl)-1-(5-methyl-2-nitrophenyl)benzimidazole
(2b). Yellow solid, yield (0.244 g, 72%), mp 157–159 uC; IR
(KBr, nmax) 3051, 1599, 1522, 1447, 1344, 1319, 1257, 1126,
1023, 826, 747 cm21; EtOAc : Pet. ether (3 : 7); Rf 0.50. 1H NMR
(300 MHz, CDCl3) d 2.45 (s, 3H), 7.13 (d, J = 7.5 Hz, 1H), 7.24–
7.38 (m, 5H), 7.43 (d, J = 10.5 Hz, 2H), 7.52 (d, J = 7.2 Hz, 1H),
7.92 (d, J = 8.1 Hz, 2H). 13C NMR (75 MHz, CDCl3) d 21.3, 109.7,
120.4, 123.2, 124.0, 125.7, 127.3, 129.3, 130.5, 130.9, 131.0,
131.4, 131.5, 132.4, 132.5, 132.6, 135.5, 142.8, 145.8, 151.1. EI-
MS m/z : 407, 409 (for 79Br, 81Br). Anal. Calcd C20H14BrN3O2; C,
58.84; H, 3.46; N, 10.29; found C, 59.09; H, 3.49; N, 10.14.
2-(2-Bromophenyl)-1-(2-nitro-4-trifluoromethylphenyl)benzi-
midazole (2c). Pale yellow solid, yield (0.288 g, 85%), mp 147–
149 uC; IR (KBr, nmax) 3068, 1618, 1543, 1445, 1381, 1321, 1256,
1180, 1142, 1088, 1031, 741, 636 cm21; EtOAc : Pet. ether
(3 : 7); Rf 0.53. 1H NMR (300 MHz, CDCl3) d 7.15 (d, J = 7.8 Hz,
1H), 7.27–7.36 (m, 2H), 7.37–7.40 (m, 1H), 7.43–7.48 (m, 2H),
7.55 (dd, J = 1.2, 7.6 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.94–8.00
(m, 2H), 8.26 (s, 1H). 13C NMR (75 MHz, CDCl3) d 109.4, 120.9,
123.3, 123.8, 124.6, 127.8, 130.5, 130.6, 130.7, 131.90, 132.2,
132.4, 132.7, 133.0, 135.2, 143.1, 145.6, 150.8. ESI-MS m/z : 462,
464 (M+H+ for 79Br, 81Br), 484, 486 (M+Na+ for 79Br, 81Br). Anal.
Calcd C20H11BrF3N3O2; C, 51.97; H, 2.40; N, 9.09; found: C,
52.24; H, 2.36; N, 9.24.
2-(2-Bromophenyl)-1-(2-nitrophenyl)-5-methylbenzimidazole
(2d). Yellow solid, yield (0.260 g, 73%), mp 165–167 uC; IR
(KBr, nmax) 2918, 1599, 1530, 1491, 1441, 1383, 1343, 1024, 950,
757, 537 cm21; EtOAc : Pet. ether (3 : 7); Rf 0.49. 1H NMR (300
MHz, CDCl3) d 2.53 (s, 3H), 7.02 (d, J = 8.4 Hz, 1H), 7.15 (d, J =
8.1 Hz, 1H), 7.22–7.31 (m, 2H), 7.43 (d, J = 7.2 Hz, 1H), 7.53 (d,
J = 7.8 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 6.9 Hz, 1H),
7.70 (d, J = 8.1 Hz, 2H), 8.00 (d, J = 8.1 Hz, 1H). 13C NMR (75
MHz, CDCl3) d 21.4, 109.1, 120.2, 123.4, 125.5, 125.6, 127.3,
129.4, 129.8, 131.0, 131.3, 132.4, 132.6, 133.04, 133.6, 134.0,
134.2, 143.1, 145.7, 151.0. ESI-MS m/z 408, 410 (M+H+ for 79Br,
81Br), 430, 432 (M+Na+ for 79Br, 81Br). Anal. calcd.
C20H14BrN3O2; C, 58.84; H, 3.46; N, 10.29; found C, 59.09; H,
3.51; N, 10.42.
Experimental section
General
Some reagents were obtained from commercial sources and
used without purification. The solvents used were of technical
grade, and freshly distilled prior to use. All melting points
were obtained on a laboratory devices melting point bath and
are uncorrected. 1H (300 MHz, 600 MHz) and 13C (75 MHz, 150
MHz) NMR spectra were recorded using CDCl3 as solvent and
tetramethyl silane (TMS) as internal standard on Bruker DPX
300 MHz and Bruker DRX 600 MHz NMR instruments at
ambient temperature. Chemical shifts are stated in parts per
million in d scales. Infrared spectra were recorded on a JASCO-
FTIR Model-410, using KBr pellets. Mass spectra were
measured in EIMS, ESIMS(+) and HRMS (ESI+) mode. EIMS
were done on a SHIMADZU GCMS (model: GCMS-QP5050A)
mass spectrometer. ESIMS and HRMS (ESI+) were done on a
Waters Micromass Q-TOF microTM Mass Spectrometer. TLC
was performed on pre-coated plates (0.25 nm, silica gel 60
F254).
A
SHIMADZU
(model
UV-1700)
UV-vis
Spectrophotometer was used for recording UV-vis spectra
keeping concentrations of the compounds at y1026 mol
dm23. The corrected fluorescence spectra were recorded with
SPEX Fluorolog II spectrofluorometer at right angle config-
uration. Fluorescence lifetimes were determined from the time
resolved fluorescence decays by the method of time-correlated
single photon counting (TCSPC) using Horiba Jobin Yvon
Fluorocube spectrofluorometer with excitation source
NanoLED-03 at 370 nm and TBX-04 detector. The instrument
response time was y1 ns.
General procedure for the synthesis of 2: 2-(2-Bromophenyl)-
1-(2-nitrophenyl)benzimidazole (2a). To the solution of benzi-
midazole 1a (0.20 g, 0.740 mmol) in acetone (7 mL), KOH
(0.082 g, 2 equiv.) was added and the reaction mixture was
stirred for 30 min. at room temperature. To this, o-fluoroni-
trobenzene (0.08 mL, 0.735 mmol) was added and the mixture
was refluxed for 4 h. Acetone was evaporated under vacuum
and the resulting reaction mixture was diluted with ethylace-
tate and washed with water and brine. The combined organic
layer was dried over sodium sulphate and evaporated under
vacuum to get the crude mixture. The crude material was
purified by column chromatography over silica gel (100–200
mesh) eluting with 12% ethylacetate in Pet. ether to get a pure
2-(2-Bromo-4-methylphenyl)-1-(2-nitrophenyl)-5-methylben-
zimidazole (2f). Yellow solid, yield (0.151 g, 72%), mp 94–96
uC; IR (KBr, nmax) 3032, 1605, 1530, 1489, 1463, 1382, 1346,
1206, 1147, 1037, 819, 788, 729 cm21; EtOAc : Pet. ether (3 : 7);
1
Rf 0.46. H NMR (300 MHz, CDCl3) d 2.30 (s, 3H), 2.52, 2.45
(26s, total 3H), 6.9–7.01 (m, 1H), 7.07 (d, J = 7.2 Hz, 1H), 7.12–
7.20 (m, 1H), 7.26–7.34 (m, 2H), 7.53–7.61 (m, 1H), 7.63–7.66
(m, 1H), 7.67–7.80 (m, 2H), 7.99 (ddd, J = 1.2, 3.3, 8.1 Hz, 1H).
1866 | RSC Adv., 2013, 3, 1862–1870
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13C NMR (75 MHz, CDCl3) d 21.0, 21.5, 109.1, 120.0, 124.8,
125.6, 128.2, 129.7, 131.1, 132.2, 133.1, 133.6, 133.9, 134.1,
135.7, 141.0, 141.9, 143.2, 145.7, 150.77, 151.0. ESI-MS m/z :
422, 424 (M+H+ for 79Br, 81Br), 444, 446 (M+Na+ for 79Br, 81Br).
Anal. calcd C21H16BrN3O2; C, 59.73; H, 3.82; N, 9.95; found; C,
60.01; H, 3.77; N, 10.09.
2-(2-Bromo-4-methylphenyl)-1-(2-nitrophenyl)benzimidazole
(2g). Yellow solid, yield (0.311 g, 73%), mp 164–166 uC; IR (KBr,
nmax) 3043, 1605, 1528, 1449, 1379, 1346, 1256, 1037, 825, 753
cm21; EtOAc : Pet. ether (3 : 7); Rf 0.50. 1H NMR (300 MHz,
CDCl3) d 2.31 (s, 3H), 7.07 (d, J = 3.9 Hz, 1H), 7.12 (d, J = 3.9 Hz,
1H), 7.29–7.32 (m, 2H), 7.35 (s, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.58
(t, J = 7.8 Hz, 1H), 7.65 (d, J = 3.9 Hz, 1H), 7.72 (t, J = 7.5 Hz,
1H), 7.93 (d, J = 3.9 Hz, 1H), 8.00 (d, J = 4.2 Hz, 1H). 13C NMR
(75 MHz, CDCl3) d 21.0, 109.6, 120.5, 123.1, 123.3, 124.0, 125.7,
127.9, 128.3, 129.6, 129.9, 131.3, 132.2, 133.2, 134.0, 135.6,
142.1, 143.0, 145.8, 151.3. ESI-MS m/z : 408, 410 (M+H+ for
79Br, 81Br), 430, 432 (M+Na+ for 79Br, 81Br). Anal. Calcd
C20H14BrN3O2; C, 58.84; H, 3.46; N, 10.29; found C, 59.14; H,
3.38; N, 10.42.
2-(2-Bromo-4-methylphenyl)-1-(2-nitro-4-trifluoromethylphe-
nyl)benzimidazole (2h). Yellow solid, yield (0.313 g, 84%), mp
128–130 uC; IR (KBr, nmax) 3062, 2318, 1616, 1544, 1450, 1382,
1321, 1256, 1181, 1141, 1095, 974, 908, 822, 743; EtOAc : Pet.
ether (3 : 7); Rf 0.48. 1H NMR (300 MHz, CDCl3) d 2.35 (s, 3H),
7.13 (d, J = 7.8 Hz, 2H), 7.31–7.44 (m, 4H), 7.83 (d, J = 8.4 Hz,
1H), 7.93–7.99 (m, 2H), 8.26 (s, 1H). 13C NMR (75 MHz, CDCl3)
d 21.0, 109.3, 120.8, 122.9, 123.3, 123.7, 124.4, 127.3, 128.6,
130.6, 132.2, 132.3, 132.8, 133.4, 135.1, 142.6, 143.1, 145.5,
151.0. ESI-MS m/z 476, 478 (M+H+ for 79Br, 81Br), 498, 500
(M+Na+ for 79Br, 81Br). Anal. Calcd. C21H13BrF3N3O2; C, 52.96;
H, 2.75; N, 8.82; found C, 53.18; H, 2.61; N, 8.96.
1-(2-Amino-5-methylphenyl)-2-(2-bromophenyl)benzimida-
zole (3b). Pale brown solid, yield (0.166 g, 90%), mp 105–107
uC; IR (KBr, nmax) 3312, 3190, 3044, 2919, 2851, 2313, 1630,
1512, 1454, 1375, 1316, 1258, 1153, 1023, 816, 751, 547 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.36. 1H NMR (300 MHz, CDCl3) d
2.14 (s, 3H), 3.52 (s, 2H), 6.70 (d, J = 8.4 Hz, 1H), 6.81 (s, 1H),
6.98 (dd, J = 1.2, 7.8 Hz, 1H), 7.19 (d, J = 7.2 Hz, 1H), 7.23–7.27
(m, 2H), 7.28–7.35 (m, 1H), 7.37–7.43 (m, 2H), 7.60 (dd, J = 1.8,
7.8 Hz, 1H), 7.93 (d, J = 7.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 20.1, 111.0, 116.5, 120.3, 120.9, 122.9, 123.5, 123.7, 126.7,
128.0, 129.2, 130.7, 130.9, 131.9, 132.0, 132.8, 135.0, 140.4,
142.8, 152.0. EI-MS m/z 377, 379 (for 79Br, 81Br). Anal. Calcd.
C20H16BrN3; C, 63.50; H, 4.26; N, 11.11; found C, 63.70; H,
4.30; N, 11.24.
1-(2-Amino-4-trifluoromethylphenyl)-2-(2-bromophenyl)ben-
zimidazole (3c). Yellow solid; yield (0.196g, 84%), mp 169–171
uC; IR (KBr, nmax) 3462, 3310, 3158, 1644, 1518, 1445, 1383,
1322, 1258, 1163, 1125, 976, 872, 752 cm21; EtOAc : Pet. ether
1
(3 : 7); Rf 0.38. H NMR (300 MHz, CDCl3) d 3.94 (s, 2H), 6.90
(d, J = 7.5 Hz, 1H), 7.04–7.10 (m, 2H), 7.18 (d, J = 6.6 Hz, 1H),
7.26–7.28 (m, 2H), 7.34–7.40 (m, 3H), 7.60 (d, J = 6.3 Hz, 1H),
7.94 (d, J = 7.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 110.9,
113.1, 114.8, 120.6, 123.4, 123.5, 123.6, 124.0, 127.0, 129.7,
131.3, 131.5, 132.0, 133.0, 134.4, 142.9, 143.1, 151.7. ESI-MS m/
z 432, 434 (M+H+ for 79Br, 81Br), 454, 456 (M+Na+ for 79Br,
81Br). Anal. Calcd C20H13BrF3N3; C, 55.57; H, 3.03; N, 9.72 ;
found C, 55.77; H, 2.99; N, 9.60.
1-(2-Aminophenyl)-2-(2-bromophenyl)-5-methylbenzimida-
zole (3d). Brown solid, yield (0.159 g, 86%), mp 99–101 uC; IR
(KBr, nmax) 3460, 3378, 3194, 3037, 2920, 2855, 1623, 1505,
1455, 1378, 1318, 1264, 1200, 1150, 1030, 977, 800, 756 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.36. 1H NMR (300 MHz, CDCl3) d
2.47, 2.53 (26s, 3H), 3.7 (brs, 2H), 6.64–6.69 (m, 1H), 6.77–6.80
(m, 1H), 6.97–7.0 (m, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.15 (d, J =
7.5 Hz, 2H), 7.20–7.28 (m, 2H), 7.38–7.41 (m, 1H), 7.58 (dd, J =
2.1, 7.5 Hz, 1H), 7.72 (s, 1H). 13C NMR (75 MHz, CDCl3) d 21.4,
110.57, 116.3, 118.2, 119.8, 120.8, 123.6, 125.0, 126.7, 129.0,
130.0, 130.8, 131.7, 131.9, 132.7, 132.7, 132.8, 142.8, 142.9,
151.8. ESI-MS m/z : 378, 380 (M+H+ for 79Br, 81Br), 400, 402
(M+Na+ for 79Br, 81Br). Anal. Calcd C20H16BrN3; C, 63.50; H,
4.26; N, 11.11; found C, 63.72; H, 4.31; N, 10.97.
General procedure for the synthesis of 3: 1-(2-Aminophenyl)-
2-(2-bromophenyl) benzimidazole (3a). To the solution of
compound 2a (0.20 g, 0.508 mmol) in AcOH (5 mL), Fe powder
(0.142 g, 2.54 mmol) was added and the reaction mixture was
heated at 90 uC for one hour. Then the reaction mixture was
cooled and poured onto ice water. The white precipitate was
filtered and the resulting solution was extracted with
ethylacetate. The organic layer was washed with saturated
bicarbonate, water and brine. The combined organic layer was
dried over sodium sulphate, filtered and concentrated under
reduced pressure to get the crude product that was further
purified by column chromatography over silica gel (100–200
mesh) eluting with 14% ethylacetate in pet. ether furnishing
3a (0.169 g, 92%), yellowish brown solid, mp 164–166 uC; IR
(KBr, nmax) 3439, 3301, 3180, 1637, 1609, 1502, 1455, 1381,
1-(2-Aminophenyl)-2-(2-bromophenyl)-6-benzoylbenzimida-
zole (3e). Pale brown solid, yield (0.142 g, 76%), mp 114–116uc;
IR (KBr, nmax) 3453, 3356, 3058, 1633, 1505, 1439, 1381, 1320,
1271, 1109, 1026, 9771, 907, 835, 727, 427 cm21; EtOAc : Pet.
ether (3 : 7); Rf 0.30. 1H NMR (300 MHz, CDCl3) d 3.68 (s, 2H),
6.68 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 8.1 Hz, 1H), 7.01 (d, J = 7.5
Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.28–7.31 (m, 2H), 7.42–7.50
(m, 3H), 7.55–7.62 (m, 2H), 7.81 (t like, J = 7.8 Hz, 4H), 7.97 (d,
J = 8.4 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 113.6, 116.7, 118.6,
119.7, 120.3, 123.5, 125.8, 126.9, 128.2, 129.0, 130.0, 130.4,
131.3, 131.4, 131.9, 132.2, 133.0, 133.2, 134.8, 138.1, 142.8,
146.0, 154.9, 196.5. ESI-MS m/z 468, 470 (M+H+ for 79Br, 81Br),
490, 492 (M+Na+ for 79Br, 81Br). Anal. Calcd C26H18BrN3O; C,
66.68; H, 3.87; N, 8.97; found C, 66.90; H, 3.91; N, 8.82.
1-(2-Aminophenyl)-2-(2-bromo-4-methylphenyl)-5-methyl-
benzimidazole (3f). Brown solid, yield (0.180 g, 87%), mp 97–
99 uC; IR (KBr, nmax) 3461, 3316, 3193, 3032, 2919, 2857, 1617,
1317, 1265, 1191, 1152, 1033, 976, 910, 831, 752, 622 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.37. 1H NMR (300 MHz, CDCl3) d
3.67 (s, 2H), 6.66 (t, J = 7.2 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 7.0
(d, J = 7.5 Hz, 1H), 7.14–7.38 (m, 7H), 7.57 (d, J = 6.6 Hz, 1H),
7.92 (d, J = 7.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 111.0,
116.4, 118.4, 120.3, 120.96, 123.0, 123.6, 123.7, 126.8, 129.1,
130.0, 130.9, 131.9, 132.0, 132.8, 134.9, 142.9, 152.0. ESI-MS m/
z: 364, 366 (M+H+ for 79Br, 81Br), 386, 388 (M+Na+ for 79Br,
81Br). Anal. Calcd C19H14BrN3; C, 62.65; H, 3.87; N, 11.54;
found C, 62.89; H, 3.82; N, 11.66.
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1503, 1460, 1380, 1315, 1264, 1203, 1151, 1036, 976, 815, 745,
605, 430 cm21; EtOAc : Pet. ether (3 : 7); Rf 0.38. 1H NMR (300
MHz, CDCl3) d 2.31 (s, 3H), 2.46 (s, 3H), 2.53 (s, 3H), 3.66 (s,
2H), 6.65–6.71 (m, 1H), 6.78–6.81 (m, 1H), 6.96–7.07 (m, 3H),
7.12–7.20 (m, 2H), 7.25–7.27 (t, J = 7.5 Hz, 1H), 7.40 (s, 1H),
7.71–7.81 (m, 1H). 13C NMR (75 MHz, CDCl3) d 21.0, 21.5,
110.5, 116.3, 118.4, 120.0, 121.2, 123.4, 124.5, 125.0, 127.6,
129.0, 129.2, 129.8, 130.0, 131.7, 133.3, 141.3, 142.9, 143.2,
152.0. ESI-MS m/z : 392, 394 (M+H+ for 79Br, 81Br), 414, 416
(M+Na+ for 79Br, 81Br). Anal. Calcd C21H18BrN3; C, 64.30; H,
4.62; N, 10.71; found C, 64.12; H, 4.67; N, 10.85.
NH), 6.90 (d, J = 7.8 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 7.14 (t, J =
7.2 Hz, 1H), 7.21–7.25 (m, 1H), 7.26–7.36 (m, 3H), 7.66 (dd, J =
14.4, 7.8, 2H), 7.89 (d, J = 7.8, 1H), 8.19 (d, J = 7.2, 1H). 13C
NMR (125 MHz, CDCl3) d 111.5, 119.5, 120.1, 121.6, 121.9,
123.1, 123.2, 123.5, 124.0, 127.7, 129.0, 130.9, 131.3, 134.8,
143.3, 144.0, 149.2, 152.3. ESI-MS m/z 284 (M+H)+; HRMS
(ESI+): calcd for C19H12N3Na [M+Na]+ 306.1007, found
306.1031.
8-Methyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine
(4b). Pale yellow solid, yield (0.148 g, 75%), mp 214–216 uC, IR
(KBr, nmax): 3270, 1602, 1516, 1461, 1373, 1309, 1267, 815, 742
cm21; EtOAc : Pet. ether (3 : 7); Rf 0.49. 1H NMR (300 MHz,
CDCl3) d 2.37 (s, 3H), 5.35 (s, 1H, NH), 6.88 (d, J = 7.8, 1H), 6.97
(d, J = 8.1, 1H), 7.04 (d, J = 8.7, 1H), 7.13 (t, J = 7.5 Hz, 1H),
7.28–7.36 (m, 3H), 7.48 (s, 1H), 7.65 (dd like, J = 2.4, 6.9 Hz,
1H), 7.87 (dd like, J = 2.4, 6.9, Hz, 1H), 8.16 (dd like, J = 1.2, 7.5
Hz, 1H). 13C NMR (75 MHz, CDCl3) d 20.6, 111.6, 119.4, 120.0,
121.6, 121.7, 123.0, 123.2, 123.4, 124.3, 128.2, 128.8, 130.9,
131.3, 133.9, 134.8, 140.7, 144.0, 149.5, 152.4. ESI-MS m/z 298
(M+H)+, 320 (M+Na)+. HRMS (ESI+) calcd for C20H15N3Na
[M+Na]+ 320.1164, found 320.1196.
7-Trifluoromethyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]-
diazepine (4c). White solid, yield (0.088 g, 54%), mp 224–226
uC, IR (neat, nmax) 2921, 1597, 1507, 1445, 1383, 1323, 1211,
1164, 1123, 1072, 746 cm21; EtOAc : Pet. ether (3 : 7); Rf 0.47.
1H NMR (600 MHz, CDCl3) d 5.54 (s, 1H, NH), 6.95 (d, J = 7.8
Hz, 1H), 7.19 (t, J = 15 Hz, 1H), 7.34 (t, J = 14.4, 2H), 7.36–7.39
(m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.80 (d,
J = 8.4 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H);
13C NMR (150 MHz, CDCl3) d 111.3, 118.9, 119.7, 120.4, 121.0,
123.7, 123.8, 124.2, 124.3, 124.4, 131.2, 131.8, 132.0, 143.0,
143.4, 148.2, 151.9. ESI-MS m/z 352 (M+H)+, 374 (M+Na)+.
HRMS (ESI+): calcd for C20H12F3N3Na [M+Na]+, 374.0881 found
374.0869.
1-(2-Aminophenyl)-2-(2-bromo-4-methylphenyl)benzimida-
zole (3g). Yellow solid; yield (0.247 g, 89%), mp 197–199 uC; IR
(KBr, nmax) 3461, 3300, 3176, 2921, 1636, 1604, 1502, 1455,
1380, 1317, 1262, 1150, 1036, 974, 821, 748, 533 cm21
;
1
EtOAc : Pet. ether (3 : 7); Rf 0.35. H NMR (600 MHz, CDCl3)
d 2.31 (s, 3H), 3.66 (s, 2H), 6.68 (t, J = 7.2 Hz, 1H), 6.80 (d, J =
8.4 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H),
7.13 (t, J = 8.4 Hz, 2H), 7.27 (d, J = 7.8 Hz, 1H), 7.31 (t like, J =
7.8 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.41 (s, 1H), 7.93 (d, J = 7.8
Hz, 1H). 13C NMR (125 MHz, CDCl3) d 21.0, 111.0, 116.4, 118.4,
120.2, 121.0, 122.9, 123.3, 123.5, 127.7, 128.7, 129.2, 129.9,
131.7, 133.3, 134.9, 141.4, 142.8, 142.9, 152.1. EI-MS m/z : 377,
379 (79Br, 81Br). Anal. Calcd C20H16BrN3 C, 63.50; H, 4.26; N,
11.11; found C, 63.77; H, 4.22; N, 11.26.
1-(2-Amino-4-trifluoromethylphenyl)-2-(2-bromo-4-methyl-
phenyl)benzimidazole (3h). Pale brown solid, yield (0.213 g,
83%), mp 144–146 uC; IR (KBr, nmax) 2666, 2315, 1633, 1516,
1447, 1383, 1325, 1258, 1167, 1127, 824, 748, 536 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.37. 1H NMR (300 MHz, CDCl3) d
2.34 (s, 3H), 3.90 (s, 2H), 6.91 (d, J = 6.9 Hz, 1H), 7.04–7.10 (m,
4H), 7.17 (d, J = 7.5 Hz, 1H), 7.30–7.37 (m, 2H), 7.40 (d, J = 8.1
Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) d
21.0, 110.9, 113.1, 113.1, 114.8, 120.5, 123.2, 123.3, 123.6,
123.8, 128.0, 128.3, 130.0, 131.7, 133.5, 134.4, 141.9, 142.8,
143.2, 151.8. EI-MS m/z 445, 447 (for 79Br, 81Br). Anal. Calcd
C21H15BrF3N3; C, 56.52; H, 3.39; N, 9.42; found C, 56.67; H,
3.44; N, 9.32.
12-Methyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine
(4d). Yellow solid, yield (0.115 g, 73%), mp 204–206 uC; IR
(KBr, nmax): 3028, 1594, 1505, 1461, 1382, 1247, 761 cm21
.
EtOAc : Pet. ether (3 : 7); Rf 0.50. 1H NMR (300 MHz, CDCl3) d
2.50 (s, 3H), 5.43 (s, major, 1H, NH), 6.89 (d, J = 6 Hz, 1H),
7.11–7.31(m, 8H), 7.44–7.74 (m, 3H), 8.15 (s, 1H); 13C NMR (75
MHz, CDCl3) d 21.5, 22.0, 112.1, 116.3, 116.5, 120.5, 123.1,
123.9, 124.0, 124.1, 124.2, 127.0, 129.8, 129.9, 130.9, 134.3,
144.5, 150.7, 172.6. ESI-MS m/z 298 (M+H)+, 320 (M+Na)+;
HRMS (ESI+): calcd for C20H15N3Na [M+Na]+, 320.1164. found
320.1199.
General procedure for the synthesis of cyclized product 4
To the stirred solution of 3a (0.150 g, 0.413 mmol) in dry
toluene (8 mL), KO-tBu (0.092 g, 2 equiv.), 1,10 phenanthroline
(10 mol%), and CuI (5 mol%) were added. Then the reaction
mixture was refluxed for 17 h under nitrogen atmosphere.
After completion of the reaction (monitored by TLC), toluene
was evaporated under vacuum, and the crude reaction mixture
was extracted with ethyl acetate (3 6 25 mL). The organic layer
was washed with water (3 6 25 mL) followed by brine (2 6 15
mL). The total organic layer was dried over sodium sulphate,
filtered, and the solvent was evaporated under reduced
pressure. The crude mass was purified by column chromato-
graphy over silica gel (100–200 mesh) eluting with 12% EtAOc
in Pet. ether to get the desired compound 4a (0.084 g, 72%
yield).
11-Benzoyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine
(4e). Pale yellow solid, yield (0.132 g, 64%), mp 191–193 uC; IR
(KBr, nmax) 2919, 1649, 1605, 1503, 1465, 1280, 903, 759 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.45. 1H NMR (300 MHz, CDCl3) d
5.5 (s, 1H, NH), 6.94 (d, J = 8.1 Hz, 1H), 7.11 (dd, J = 7.5, 1.5 Hz,
1H), 7.19 (d, J = 8.7 Hz, 1H), 7.24–7.30 (m, 2H), 7.35–7.41 (m,
1H), 7.50 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.65–7.68 (m, 1H),
7.76–7.84 (m, 3H), 7.90 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 1.2 Hz,
1H), 8.21 (s, 1H); 13C NMR (75 MHz, CDCl3) d 114.2, 119.4,
119.7, 121.2, 122.1, 123.7, 124.2, 124.5, 126.2, 128.2, 128.3,
128.6, 130.0, 131.2, 132.0, 132.1, 132.7, 134.8, 138.2, 143.4,
147.2, 149.6, 155.3, 196.5. ESI-MS m/z 388 (M+H)+, 410
5H-Benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine (4a). Pale
yellow solid, yield (0.084 g, 72%), mp 198–200 uC; IR (KBr, nmax
)
3276, 1607, 1502, 1458, 1385, 1258, 746 cm21; EtOAc : Pet.
1
ether (3 : 7); Rf 0.48. H NMR (600 MHz, CDCl3) d 5.49 (s, 1H,
1868 | RSC Adv., 2013, 3, 1862–1870
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(M+Na)+. HRMS (ESI+): calcd for C26H17N3ONa [M+Na]+,
410.1269. found 410.1305.
2 R. B. Silverman, The Organic Chemistry of Drug Design and
Drug Action, Elsevier Academic Press, Oxford, 2nd edn,
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3 D. Lednicer, Strategies for Organic Drug Synthesis and
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3,12-Dimethyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]diaze-
pine (4f). Pale yellow solid, yield (0.088 g, 74%), mp 183–185
uC; IR (KBr, nmax) 3201, 3024, 2921, 1611, 1507, 1456, 1375,
1323, 1249, 809, 758 cm21; EtOAc : Pet. ether (3 : 7); Rf 0.48.
1H NMR (300 MHz, CDCl3) d 2.34 (s, 3H), 2.49, 2.50 (26s, 3H),
5.33 (s, 1H, NH), 6.72 (s, 1H), 6.96 (d, J = 7.8 Hz, 1H), 7.07 (d, J
= 7.5 Hz, 2H), 7.12–7.26 (m, 2H), 7.43–7.74 (m, 3H), 8.04 (d, J =
7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) d 21.2, 21.5, 21.9, 111.0,
111.4, 119.4, 119.7, 120.0, 121.7, 123.9, 124.0, 124.44, 124.5,
124.7, 127.5, 129.2, 129.3, 130.7, 141.8, 143.1, 148.9, 148.9. ESI-
MS m/z 312 (M+H)+, 334 (M+Na)+. HRMS (ESI+): calcd for
C21H17N3Na [M+Na]+, 334.1320; found 334.1339.
4 P. Helissey, S. Cros and S. Giorgi-Renault, Anti-Cancer Drug
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6 R. Pflantz, J. Sluiter, M. Kricka, W. Saak, C. Hoenke and
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10 H. J. Breslin, M. J. Kukla, D. W. Ludovici, R. Mohrbacher,
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11 M. J. Kukla, H. J. Breslin, C. J. Diamond, P. P. Grous, C.
Y. Ho, M. Miranda, J. D. Rodgers, R. G. Sherrill, E. de
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12 M. K. Dawood and B. F. Abdel-Wahab, Arkivoc, 2010,
333–389 and the references cited therein.
13 S. Mitra, T. S. Banerjee, S. K. Hota, D. Bhattacharya, S. Das
and P. Chattopadhyay, Eur. J. Med. Chem., 2011, 46,
1713–1720 and the references cited therein.
14 N. D. Adhikary and P. Chattopadhyay, Eur. J. Org. Chem.,
2010, 1754–1762.
15 A. Neogi, T. P. Majhi, B. Achari and P. Chattopadhyay, Eur.
J. Org. Chem., 2008, 330–336.
16 T. P. Majhi, A. Neogi, S. Ghosh, A. K. Mukherjee,
M. Helliwell and P. Chattopadhyay, Synthesis, 2008,
94–100.
17 A. Neogi, T. P. Majhi, R. Mukhopadhyay and
P. Chattopadhyay, J. Org. Chem., 2006, 71, 3291–3294.
18 J. P. Wolfe, S. Wagaw and S. L. Buchwald, J. Am. Chem. Soc.,
1996, 118, 7215–7216.
3-Methyl-5H-benzimidazo[1,2-d]dibenzo[b,f][1,4]diazepine
(4g). Pale yellow solid, yield (0.158 g, 73%), mp 267–269 uC; IR
(KBr, nmax): 3269, 1606, 1506, 1451, 1320, 1263, 813, 755 cm21
;
EtOAc : Pet. ether (3 : 7); Rf 0.49. 1H NMR (300 MHz, CDCl3) d
2.33 (s, 3H), 5.36 (s, 1H, NH), 6.72 (s, 1H), 6.96 (d, J = 8.1 Hz,
1H) , 7.07 (dd, J = 1.2, 7.2 Hz, 1H), 7.16–7.25 (m, 2H), 7.27–7.35
(m, 2H), 7.65 (t, J = 8.7 Hz, 2H), 7.85 (d, J = 7.5 Hz, 1H), 8.06 (d,
J = 8.1 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 21.2, 111.5, 118.7,
119.9, 120.1, 121.8, 123.0, 123.2, 123.9, 124.0, 124.5, 127.6,
129.0, 130.8, 134.8, 142.0, 143.3, 144.0, 149.1, 152.5. ESI-MS m/
z 298 (M+H)+, 320 (M+Na)+. HRMS (ESI+): calcd for C20H15N3Na
[M+Na]+, 320.1164; found 320.1195.
3-Methyl-7-trifluoromethyl-5H-benzimidazo[1,2-d]diben-
zo[b,f][1,4]diazepine (4h). Yellow solid, yield (0.163 g, 57%),
mp 241–243 uC; IR (KBr, nmax) 3228, 1611, 1508, 1451, 1378,
1329, 1227, 1171, 1127, 980, 886, 815, 744 cm21; EtOAc : Pet.
ether (3 : 7); Rf 0.48. 1H NMR (300 MHz, CDCl3) d 2.36 (s, 3H),
5.48 (s, 1H, NH), 6.76 (s, 1H), 7.0 (d, J = 7.8 Hz, 1H), 7.28–7.38
(m, 3H), 7.45 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.79 (d,
J = 8.1 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H).
13C NMR (75 MHz, CDCl3) d 21.2, 111.3, 118.6, 118.8, 118.9,
120.3, 120.8, 120.9, 123.5, 123.7, 124.3, 125.0, 129.4, 131.0,
132.2, 134.6, 142.5, 143.5, 144.2, 148.1, 152.1. EI-MS m/z 365;
HRMS (ESI+): calcd for C21H15F3N3 [M+H]+ , 366.1218; found
366.1239.
19 E. M. Beccalli, G. Broggini, G. Paladino and C. Zoni,
Tetrahedron, 2005, 61, 61–68.
Acknowledgements
20 L. Basolo, E. M. Beccalli, E. Borsini, G. Broggini,
M. Khansaa and M. Rigamonti, Eur. J. Org. Chem., 2010,
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21 B. Schlummer and U. Scholz, Adv. Synth. Catal., 2004, 346,
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22 For copper catalyzed intramolecular aryl amination see: Y.
M. Zhu, L. N. Qin, R. Liu, S. J. Ji and H. Katayama,
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Financial support from the Department of Science and
Technology (DST), New Delhi, Government of India is grate-
fully acknowledged. S. M. thanks the Council of Scientific and
Industrial Research (CSIR) for providing a senior research
fellowship (SRF). We acknowledge Dr G. S. Kumar for
providing us the UV-vis spectrophotometer and Dr B. Achari
for his valuable suggestions.
23 G. Evindar and R. A. Batey, Org. Lett., 2003, 5, 133–136.
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