A mild and expedient one-pot synthesis of substituted benzimidazoles in water using a phase-transfer catalyst

Article abstract of DOI:10.1007/s00706-008-0036-z

1-Alkyl/phenyl-2-arylbenzimidazoles have been synthesized in very good to excellent yields by a one-pot condensation of N-alkyl/phenyl-o-phenylenediamines with aryl aldehydes in water at room temperature using cetylpyridinium bromide as a cheap and eco-friendly catalyst.

Full text of DOI:10.1007/s00706-008-0036-z

Monatsh Chem (2009) 140:375–380
DOI 10.1007/s00706-008-0036-z
ORIGINAL PAPER
A mild and expedient one-pot synthesis of substituted
benzimidazoles in water using a phase-transfer catalyst
Manas Chakrabarty Æ Sulakshana Karmakar Æ
Ratna Mukherjee Æ Shiho Arima Æ Yoshihiro Harigaya
Received: 6 May 2008 / Accepted: 1 July 2008 / Published online: 4 September 2008
Ó Springer-Verlag 2008
Abstract 1-Alkyl/phenyl-2-arylbenzimidazoles have been
synthesized in very good to excellent yields by a one-pot
condensation of N-alkyl/phenyl-o-phenylenediamines with
aryl aldehydes in water at room temperature using cetyl-
pyridinium bromide as a cheap and eco-friendly catalyst.
gained more popularity due to the availability of a wide
range of aryl aldehydes. Although a variety of reagents/
catalysts have been recently employed in this second route
[21–34], many of these methods use preformed, expensive,
lachrymatory or hygroscopic reagents, highly inflammable
or potentially explosive solvents, high temperatures, and/or
require long reaction times. In continuation of our interest
in developing novel syntheses of condensed heterocycles
with proven or potential bioactivities [35–41], we planned
to find out a suitable catalyst and conditions for the syn-
thesis of substituted benzimidazoles via the second route,
but with better efficacy and without the difficulties cited
above. Since the rates of organic reactions are accelerated
in water [42, 43] and since the phase transfer catalysts
(PTCs) are well known as constituting one of the most
efficient ways of avoiding waste generation [44–46], our
plan was to carry out the reactions in water using a PTC.
Although a few water-mediated reactions have been
reported very recently for the synthesis of 2-aryl-1-arylm-
ethylbenzimidazoles [47, 48] and 2-arylbenzimidazoles
[49, 50], there was still room for improvement of reaction
conditions. Therefore, we continued our efforts, and as a
result, we have been able to develop a mild and highly
efficient synthesis of 1,2-disubstituted benzimidazoles by
the condensation of N-alkyl/aryl-o-PDs with aryl aldehydes
in water using cetylpyridinium bromide, a PTC. Our find-
ings are presented briefly in this communication.
Keywords Benzimidazoles ꢀ Synthesis ꢀ
N-alkyl/phenyl-o-phenylenediamines ꢀ Aryl aldehydes ꢀ
Phase-transfer catalyst
Introduction
Since the discovery of thiabendazole in 1960 [1], benz-
imidazoles have been widely used as anthelmintics in
veterinary medicine as well as in human therapeutics [2–4].
They also display significant antiviral [5–9], antiulcerative,
antiinflammatory, antihistaminic [10–12], and anticancer
[13, 14] properties and are considered as privileged sub-
structures in drug design because of their strong affinity to
various enzymes and protein receptors [15, 16]. The ear-
liest route to this class of molecules involves the reaction of
o-phenylenediamines (o-PDs) with carboxylic acids,
nitriles, amidates, or orthoesters under strongly acidic or
harsh dehydrating conditions [17–20]. The second route,
comprising the reaction of o-PDs with aryl aldehydes, has
M. Chakrabarty (&) ꢀ S. Karmakar ꢀ R. Mukherjee
Department of Chemistry, Bose Institute,
93/1, A. P. C. Road, Kolkata 700009, India
e-mail: chakmanas@yahoo.co.in
Results and discussion
Our previous experience in the synthesis of benzimidazoles
via this route, but using other catalysts dictated that 1.5
equivalents of the aryl aldehydes would be required
for reactions with o-PD itself. Hence, a mixture of o-PD
S. Arima ꢀ Y. Harigaya
School of Pharmaceutical Sciences, Kitasato University,
Minato-ku, Tokyo 108, Japan
123

376
M. Chakrabarty et al.
(1a, 1 mmol) and benzaldehyde (2a0, 1.5 mmol) in water
was stirred at room temperature in the absence of any
catalyst when the reaction started progressing (TLC), but at
an unacceptably slow rate. The reaction was, therefore,
repeated using 5 mol% of each of five PTCs, viz. tetra-n-
butylammonium bromide (TBAB), cetyltrimethylammo-
nium bromide (CTAB), benzyltriethylammonium chloride
(BTAC), cetylpyridinium bromide (CPB), and tetra-n-
butylammonium hydrogensulfate (TBAHS) separately as
catalysts. In each case, the same mixture of two products
was formed (TLC). These products were identified as 2-
phenylbenzimidazole (3) and 1-benzyl-2-phenylbenzimi-
dazole (4) by direct comparison (mp, mixed mp, and co-
TLC) with the same compounds prepared earlier in our
laboratory [37]. The results (Scheme 1; Table 1) pin-
pointed CPB to be the catalyst of our choice in terms of
both reaction period and overall yield of the products. In
order to check the influence, if any, of a higher proportion
of the aryl aldehyde, the reaction of o-PD (1a) with
two equivalents of 2a0 was repeated under similar condi-
tions when the same products 3 and 4 were isolated in
52 and 35% yields, respectively (not detailed in the
‘‘Experimental’’).
Table 1 Effect of PTCs (5 mol%) on the reaction of o-PD (1a;
1 mmol) with benzaldehyde (2a0; 1.5 mmol) in water at rt
PTC
Time (h)
Yield (%)
Overall yield (%)
3
4
TBAB
CTAB
BTAC
CPB
3
36
40
–
28
32
–
64
72
–
1
Incompletea
0.5
Incompletea
52
–
30
–
82
–
TBAHS
a
Incomplete even after 6 h (TLC)
IR, 1H and 13C NMR (PND, DEPT 135), LR and HR
EI-MS data besides elemental analyses. The reactions have
been shown in Scheme 2 and the results in Table 2.
Elemental analyses
Compound Molecular
formula
Expected
Observed
C
H
N
C
H
N
5ca0
5cb0
5cc0
5cd0
5ce0
5db0
5dc0
5dd0
5de0
C16H16N2
81.36 6.78 11.86 81.42 6.76 11.83
C17H18N2O 76.69 6.77 10.53 76.77 6.75 10.56
C16H15N2Br 60.95 4.76 8.89 60.71 4.76 8.83
C16H15N3O2 68.33 5.34 14.95 68.38 5.32 14.99
C14H14N2S 69.42 5.78 11.57 69.48 5.77 11.61
C20H16N2O 80.00 5.33 9.33 79.93 5.35 9.36
C19H13N2Br 65.33 3.72 8.02 65.31 3.71 8.05
C19H13N3O2 72.38 4.13 13.33 72.44 4.14 13.29
C17H12N2S 73.91 4.35 10.14 73.86 4.34 10.18
Since many of the 1-substituted-2-arylbenzimidazoles
exhibit significant bioactivities, e.g., the antihypertensive
drug telmisartan (Micardis) [51], and since they can be
obtained by the condensation of N-substituted-o-PDs with
aryl aldehydes, each of N-methyl, N-iso-propyl and N-
phenyl-o-PDs (1b–1d, respectively; 1 mmol each) was
allowed to react separately with each of the five aromatic
aldehydes (2a0–2e0; 1 mmol each since equimolar amounts
of the aldehydes were found to consume 1b–1d com-
pletely) in water at room temperature using 5 mol% of
CPB as the catalyst. As expected, the respective 1-alkyl/
phenyl–2-arylbenzimidazoles (5ba0–5be0, 5ca0–5ce0, 5da0–
5de0) were obtained as the sole products and isolated in 65–
100% yields. The known compounds (5ba0–5be0, 5da0)
were identified by comparing their melting points with
Clearly, the reactions of both 2d0 and 2e0 with all the
three o-PDs (1b–1d) were noticeably slow. In order to
ascertain the effect of a higher concentration of the PTC on
these reactions, each of both 2d0 and 2e0 was allowed to
react separately with each of 1b–1d on a similar scale in
water at room temperature, but using 20 mol% of CPB.
1
those reported in the literature and supportive H NMR
spectroscopic data. All the nine new compounds
(5ca0–5ce0, 5db0–5de0) were identified by analysing their
CPB (5 mol%)
NH2
N
H2O, rt
ArCHO
2a'-2e'
+
Ar
5 min - 6 h
65-100%
N
R
NH2
NHR
1b-1d
5ba'-5be', 5ca'-5ce',
5da'-5de'
NH2
1a
N
N
N
5 mol% PTC
Ph
Ph
Ph
+
+
Throughout:
H2O, rt
N
H
N
PhCHO
R = H (a), Me (b), iPr (c), Ph (d)
Ar = Ph (a'), 4-OCH3C6H4 (b'),
4-BrC6H4 (c'), 4-NO2C6H4(d'),
2-thienyl (e')
Et
N
Ph
2a'
3
4
6
PTC : TBAB, CTAB, BTAC, CPB, TBAHS
Scheme 1
Scheme 2
123

Mild and expedient one-pot synthesis of substituted benzimidazoles
377
Table 2 Reactions of N-alkyl/
Entry
o-PD (1)
ArCHO (2)
Time (min)
Product: yield (%)a
mp (°C) found (reported)
phenyl-o-PDs (1 mmol) with
aryl aldehydes (1 mmol) in
presence of 5 mol% of CPB in
water at rt
1
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
1d
1d
1d
1d
1d
2a0
2b0
2c0
2d0
2e0
2a0
2b0
2c0
2d0
2e0
2a0
2b0
2c0
2d0
2e0
5
5ba0: 77
5bb0: 82
5bc0: 100
5bd0: 95
5be0: 89
5ca0: 72
5cb0: 80
5cc0: 95
5cd0: 93
5ce0: 83
5da0: 80
5db0: 85
5dc0: 90
5dd0: 89
5de0: 65
96–98 (97–98)b
117–118 (118–120)b
107–109 (109–110)b
210–212 (204–206)b
81–83 (83–84)b
150–152 (–)
2
30
3
45
4
1.75 h
1.25 h
5
5
6
7
30
150–151 (–)
8
30
141–143 (–)
9
2.5 h
1.5 h
5
154–156 (–)
10
11
12
13
14
15
111–113 (–)
111–112 (110–112)b
30
126–128 (–)
30
162–164 (–)
a
Yields of isolated pure
products
4 h
6 h
175–176 (–)
125–126 (–)
b
Ref. [36]
The outcome (Table 3), not detailed in the ‘‘Experimen-
tal,’’ reflected that the reactions were faster, although the
yields of the products were comparable to those obtained
using 5 mol% of the catalyst.
(7), which then undergo CPB-catalysed cyclisation to form
the unisolable 1-alkyl/phenyl-2-arylbenzimidazolines (8).
Subsequent aerial oxidation of the latter, taking place
during the reactions and workups, results in the formation
of the benzimidazoles 5 (Scheme 3).
In order to check the applicability of the present method
in the case of alkyl aldehydes, N-phenyl-o-PD (1d,
1 mmol) was treated with n-propanal (1 mmol) in the
presence of 5 mol% of CPB in water at room temperature
(not detailed in the ‘‘Experimental’’). It furnished, as
expected, 2-ethyl-1-phenylbenzimidazole (6) [52, 53],
To conclude, we have demonstrated that 5 mol%, or
better, 20 mol% of CPB in water at room temperature is a
mild and highly efficient catalyst for a one-pot synthesis of
1-substituted-2-arylbenzimidazoles from N-alkyl/phenyl-o-
PDs and aryl aldehydes. In a recent report on the thermal
one-pot synthesis of 2-arylbenzimidazoles by the oxidative
condensation of o-PDs with aryl aldehydes using sodium
metabisulphite as the oxidant, the presence of an electron-
withdrawing group (CF3) and an electron-donating group
(CH3) separately in the benzene ring of o-PD was reported
to decelerate and accelerate the reactions, respectively [54].
A similar observation was expected in our case as well,
which, however, we did not study. The fact that CPB,
acting like a surfactant, increases the substrate concentra-
tion at air-water interface, explains the observed efficacy of
1
identified mainly by its H and 13C NMR spectroscopic
data (vide ‘‘Experimental’’), in 80% yield. But the reaction
took about 24 h for completion, which suggested that al-
kanals are not useful substrates for the present method.
Based on the current state of knowledge on the mech-
anism of formation of 2-arylbenzimidazoles from the
condensation of o-PDs with aryl aldehydes [30, 32], the
following mechanism of formation of compounds 5 may be
envisaged. N-Alkyl/phenyl-o-PDs (1b–1d) condense with
aryl aldehydes to form the corresponding monoimines
Table 3 Reactions of 1b–1d (1 mmol) with 2d0 and 2e0 (1 mmol)
using 20 mol% of CPB in water at rt
CHAr
N
NH2
+
ArCHO
NHR
NHR
Entry 1 ? 2
Time using CPB (h) Product Yield (%) using
20 mol% 5 mol% 20 mol% 5 mol%
7
2
1b-1d
CPB-cat.
1
2
3
4
5
6
1b ? 2d0
1b ? 2e0
1c ? 2d0
1c ? 2e0 1.25
1d ? 2d0 2.5
1d ? 2e0
1
1
2
1.75
1.25
2.5
1.5
4
5bd0
5be0
5cd0
5ce0
5dd0
5de0
95
90
95
85
91
66
95
89
93
83
89
65
H
N
N
O2 (air)
Ar
Ar
N
R
N
R
8
5
1
6
Scheme 3
123

378
M. Chakrabarty et al.
General procedure for the synthesis of benzimidazoles 5
our PTC-mediated aqueous method. Although CPB could
not be recovered due to its high solubility in water, this
aspect is more than compensated by the fact that CPB is
quite inexpensive. Thus, our method constitutes a viable
alternative to the few existing water-based methodologies
[47–50].
To a mixture of N-alkyl/phenyl-o-PD (1 mmol) and aryl
aldehyde (1 mmol) in water (5 cm3) was added 0.019 g
cetylpyridinium bromide (5 mol%). The mixture was stir-
red at rt until the reaction was over (TLC). The solution
was then poured into brine, warmed a little to break the
emulsion, and extracted with EtOAc (3 9 15 cm3). The
pooled solvent extracts were washed with water, dried
(Na2SO4), and the solvent distilled off. The residues were
purified by CC using EtOAc-PE (5–20%) as eluent to
afford pure benzimidazoles 5.
Experimental
Melting points were recorded on a Toshniwal apparatus.
The IR spectra were recorded on Nicolet Impact 410 or
Perkin-Elmer RX 1 FT-IR spectrophotometers, the 1H
(500 MHz) and 13C (125 MHz) NMR spectra, including
DEPT-135, on a BRUKER DRX-500 NMR spectrometer
and the LR and HR EI-MS on JEOL JMS-AX505HA and
JEOL JMS-700 MStation mass spectrometers, respectively.
The nine new compounds (5ca0, 5cb0, 5cc0, 5cd0, 5ce0, 5db0,
5dc0, 5dd0, 5de0) were subjected to elemental analysis in a
Perkin Elmer 2400 Series II C, H, N Analyzer, and the
results were found to be in good agreement with the cal-
culated values. Thin-layer chromatographies (TLC) were
carried out on silica gel G (Merck, India) plates and col-
umn chromatographies (CC) on silica gel (60–120 mesh,
Qualigens, India). PE refers to petroleum ether, bp
60–80 °C. N-Methyl and N-phenyl-o-PDs were procured
from Aldrich.
2-Phenyl-1-iso-propylbenzimidazole (5ca0, C16H16N2)
White crystals (0.17 g, 72%); Rf = 0.42 (PE-EtOAc, 4:1);
ꢀ
mp 150–152 °C; IR (nujol): m = 1600, 1281, 1162, 1135,
1102, 1016, 777, 751, 704 cm-1 1H NMR (500 MHz,
;
CDCl3): d = 1.65 (d, J = 7 Hz, 6H), 4.82 (septet,
J = 7 Hz, 1H), 7.23–7.32 (m, 2H), 7.48–7.54 (m, 3H),
7.59–7.68 (m, 3H), 7.80–7.86 (m, 1H) ppm; 13C NMR
(125 MHz): d = 21.8 (CH3), 49.1, 112.6, 120.7, 122.4,
122.6, 129.0, 129.8, 130.0 (all CH), 131.5, 133.9, 144.2,
154.0 (all C) ppm; LR EI-MS: m/z (%) = 236 (M?, 69),
235 (20), 222 (12), 221 (54), 195 (17), 194 (100), 193 (32),
77 (16); HR EI-MS calcd for C16H16N2, 236.1313 (M)?,
found 236.1314.
2-(4-Methoxyphenyl)-1-iso-propylbenzimidazole
(5cb0, C17H18N2O)
Off-white crystals (0.213 g, 80%); Rf = 0.48 (PE-EtOAc,
Reaction of o-PD (1a) with benzaldehyde (2a0)
ꢀ
1:1); mp 150–151 °C; IR (nujol): m = 1659, 1606, 1281,
1
1255, 1182, 1155, 1036, 850, 758, 612 cm-1; H NMR
A mixture of o-PD (1 mmol) and benzaldehyde (1.5 mmol)
was treated separately with 5 mol% of each of the five
different PTCs (TBAB, CTAB, BTAC, CPB, and TBAHS) in
water at rt. After the reaction was over (TLC), viz. in the
cases of TBAB, CTAB, and CPB or incomplete even after
6 h, viz. for BTAC and TBAHS, the reaction was terminated
by adding brine to it, followed by warming the solution a
little to break the emulsion and then extracting it with
EtOAc (3 9 15 cm3). The pooled solvent extracts were
washed with water, dried (Na2SO4), and the solvent distilled
off. The residue, a mixture of two products (TLC), was
separated into its constituents, viz. 2-phenylbenzimidazole
(3) (Rf = 0.49) and 1-benzyl-2-phenylbenzimidazole (4)
(Rf = 0.63) by preparative TLC (double development) in
PE-benzene-EtOAc (2:2:1).
(500 MHz, CDCl3): d = 1.64 (d, J = 7 Hz, 6H), 3.87 (s,
3H), 4.82 (septet, J = 7 Hz, 1H), 7.03 (d, J = 9 Hz, 2H),
7.24 (td, J1 = 7 Hz, J2 = 1.5 Hz, 1H), 7.27 (td,
J1 = 7 Hz, J2 = 1.5 Hz, 1H), 7.58 (d, J = 9 Hz, 2H),
7.59–7.62 (m, 1H), 7.79–7.82 (m, 1H) ppm; 13C NMR
(125 MHz): d = 21.8, 55.8 (CH3), 49.1, 112.6, 114.5,
120.5, 122.2, 122.4, 131.2 (all CH), 123.7, 133.9, 144.2,
153.9, 161.0 (all C) ppm; LR EI-MS: m/z (%) = 266 (M?,
100), 265 (32), 251 (37), 224 (84), 223 (38), 180 (21), 133
(34), 103 (11), 77 (16); HR EI-MS calcd for C17H18N2O,
266.1419 (M)?, found 266.1421.
2-(4-Bromophenyl)-1-iso-propylbenzimidazole
(5cc0, C16H15N2Br)
Light cream crystals (0.3 g, 95%); Rf = 0.55 (PE-EtOAc,
ꢀ
7:3); mp 141–143 °C; IR (KBr): m = 1593, 1449, 1398,
Preparation of N-iso-propyl-o-PD (1c)
1281, 1130, 1068, 1003, 838, 742 cm-1 1H NMR
;
(500 MHz, CDCl3): d = 1.65 (d, J = 7 Hz, 6H), 4.76
(septet, J = 7 Hz, 1H), 7.28 (dd, J1 = 9 Hz, J2 = 2 Hz,
2H), 7.52 (d, J = 8.5 Hz, 2H), 7.60–7.64 (m, 1H), 7.66 (d,
J = 8.5 Hz, 2H), 7.80–7.84 (m, 1H) ppm; 13C NMR
(125 MHz): d = 21.8 (CH3), 49.3, 112.7, 120.8, 122.6,
N-Iso-propyl-o-PD was prepared in 90% yield in a two-
step process from o-nitroaniline by alkylation with iso-
propyl bromide in DMSO/NaH [55, 56], followed by
reduction of the product by SnCl2 [57]. It was identified by
1
its H NMR spectroscopic data [58].
123

Mild and expedient one-pot synthesis of substituted benzimidazoles
379
122.9, 131.4, 132.3 (all CH), 124.6, 130.4, 133.9, 144.1,
152.8 (all C) ppm; LR EI-MS: m/z (%) = 316 (M??2, 97),
315 (35), 314 (M?, 100), 313 (17), 301 (16), 299 (18), 274
(98), 273 (47), 272 (97), 271 (32), 235 (18), 220 (71), 219
(34), 193 (75), 192 (71), 77 (24); HR EI-MS calcd for
C16H15N279Br, 314.0419 (M)?, found 314.0421; calcd for
C16H15N281Br, 316.0398, found: 316.0401.
299 (80), 285 (5), 256 (30), 77 (7); HR EI-MS calcd for
C20H16N2O, 300.1262 (M)?, found 300.1268.
2-(4-Bromophenyl)-1-phenylbenzimidazole
(5dc0, C19H13N2Br)
White crystals (0.312 g, 90%); Rf = 0.61 (PE-EtOAc, 4:1);
ꢀ
mp 162–164 °C; IR (nujol): m = 1600, 1500, 1407, 1328,
1268, 1102, 1069, 1009, 976, 837, 744, 704 cm-1 1H
;
2-(4-Nitrophenyl)-1-iso-propylbenzimidazole
(5cd0, C16H15N3O2)
Pale yellow crystals (0.26 g, 93%); Rf = 0.41 (PE-EtOAc,
NMR (500 MHz, CDCl3): d = 7.23 (ddd, J1 = 8 Hz,
J2 = 1 Hz, J3 = 0.5 Hz, 1H), 7.26 (dd, J1 = 7 Hz,
J2 = 1 Hz, 1H), 7.28–7.32 (m, 1H), 7.30 (dd, J1 = 7 Hz,
J2 = 2 Hz, 1H), 7.34 (ddd, J1 = 8 Hz, J2 = 7 Hz,
J3 = 1 Hz, 1H), 7.42–7.45 (m, 5H), 7.48–7.54 (m, 1H),
7.51 (d, J = 7 Hz, 1H), 7.88 (d, J = 8 Hz, 1H) ppm; 13C
NMR (125 MHz): d = 110.9, 120.3, 123.5, 124.0, 127.7,
129.2, 130.4, 131.2, 131.9 (all CH), 124.4, 129.3, 137.1,
137.6, 143.3, 151.6 (all C) ppm; LR EI-MS: m/z
(%) = 350 (M??2, 96), 349 (97), 348 (M?, 100), 347
(82), 268 (32), 267 (20), 77 (11); HR EI-MS calcd for
C19H13N279Br, 348.0262 (M)?, found 348.0254; calcd for
C19H13N281Br, 350.0241, found 350.0243.
ꢀ
4:1); mp 154–156 °C; IR (KBr): m = 1706, 1598, 1521,
1
1452, 1404, 1345, 1246, 1105, 1011, 858, 744 cm-1; H
NMR (500 MHz, CDCl3): d = 1.70 (d, J = 7 Hz, 6H),
4.78 (septet, J = 7 Hz, 1H), 7.34 (dd, J1 = 6 Hz,
J2 = 3 Hz, 1H), 7.67 (dd, J1 = 6 Hz, J2 = 3 Hz, 1H),
7.87 (d, J = 8.5 Hz, 2H), 7.88 (d, J = 9 Hz, 1H), 8.25 (d,
J = 9 Hz, 1H), 8.39 (d, J = 8.5 Hz, 2H) ppm; 13C NMR
(125 MHz): d = 21.9 (CH3), 49.7, 113.0, 120.9, 123.2,
123.7, 124.3, 130.9 (all CH), 133.9, 137.4, 143.8, 148.9,
151.2 (all C) ppm; LR EI-MS: m/z (%) = 281 (M?, 100),
266 (32), 239 (75), 193 (66); HR EI-MS calcd for
C16H15N3O2, 281.1165 (M)?, found 281.1164.
2-(4-Nitrophenyl)-1-phenylbenzimidazole
(5dd0, C19H13N3O2)
Yellow crystals (0.28 g, 89%); Rf = 0.41 (PE-EtOAc,
1-Iso-propyl-2-(2-thienyl)benzimidazole
(5ce0, C14H14N2S)
Light brown crystals (0.2 g, 83%); Rf = 0.45 (PE-EtOAc,
ꢀ
17:3); mp 175–176 °C; IR (nujol): m = 1600, 1513, 1343,
1
1102, 976, 857, 771, 744, 704 cm-1; H NMR (500 MHz,
ꢀ
7:3); mp 111–113 °C; IR (nujol): m = 1613, 1553, 1421,
CDCl3): d = 7.26 (d, J = 8 Hz, 1H), 7.29–7.35 (m, 3H),
7.38 (td, J1 = 7 Hz, J2 = 1 Hz, 1H), 7.51–7.58 (m, 3H),
7.76 (d, J = 9 Hz, 2H), 7.91 (d, J = 8 Hz, 1H), 8.15 (d,
J = 9 Hz, 2H) ppm; 13C NMR (125 MHz): d = 111.1,
120.7, 123.9, 124.0, 124.8, 127.7, 129.6, 130.4, 130.6 (all
CH), 136.5, 136.8, 137.8, 143.3, 148.4, 150.0 (all C) ppm;
LR EI-MS: m/z (%) = 315 (M?, 100), 314 (35), 285 (15),
284 (15), 269 (16), 268 (55), 267 (19), 77 (6); HR EI-MS
calcd for C19H13N3O2, 315.1007 (M)?, found 315.0996.
1281, 1155, 1116, 996, 857, 751, 724 cm-1 1H NMR
;
(500 MHz, CDCl3): d = 1.69 (d, J = 7 Hz, 6H), 5.11
(septet, J = 7 Hz, 1H), 7.18 (dd, J1 = 5.5 Hz,
J2 = 3.5 Hz, 1H), 7.25 (td, J1 = 7 Hz, J2 = 2 Hz, 1H),
7.27 (td, J1 = 7 Hz, J2 = 2 Hz, 1H), 7.40 (dd,
J1 = 3.5 Hz, J2 = 1 Hz, 1H), 7.52 (dd, J1 = 5.5 Hz,
J2 = 1 Hz, 1H), 7.58–7.63 (m, 1H), 7.79–7.83 (m, 1H)
ppm; 13C NMR (125 MHz): d = 21.8 (CH3), 49.2, 112.6,
120.7, 122.6, 122.8, 127.9, 128.82, 128.85 (all CH), 132.6,
134.2, 144.2, 147.6 (all C) ppm; LR EI-MS: m/z
(%) = 242 (M?, 75), 227 (25), 200 (100); HR EI-MS
calcd for C14H14N2S, 242.0878 (M)?, found 242.0890.
1-Phenyl-2-(2-thienyl)benzimidazole (5de0, C17H12N2S)
Cream coloured crystals (0.18 g, 65%); Rf = 0.45 (PE-
ꢀ
EtOAc, 17:3); mp 125–126 °C; IR (nujol): m = 1650, 1600,
1228, 1162, 1069, 970, 857, 811, 738 cm-1 1H NMR
;
2-(4-Methoxyphenyl)-1-phenylbenzimidazole
(5db0, C20H16N2O)
Cream coloured crystals (0.256 g, 85%); Rf = 0.41 (PE-
(500 MHz, CDCl3): d = 6.85 (dd, J1 = 3.5 Hz,
J2 = 1 Hz, 1H), 6.9 (dd, J1 = 5 Hz, J2 = 4 Hz, 1H),
7.06 (dd, J1 = 8 Hz, J2 = 1 Hz, 1H), 7.21 (ddd,
J1 = 8 Hz, J2 = 7 Hz, J3 = 1 Hz, 1H), 7.30 (ddd,
J1 = 8.5 Hz, J2 = 7 Hz, J3 = 1 Hz, 1H), 7.34 (dd,
J1 = 5 Hz, J2 = 1 Hz, 1H), 7.40–7.43 (m, 2H), 7.57–
7.61 (m, 3H), 7.85 (d, J = 8 Hz, 1H) ppm; 13C NMR
(125 MHz): d = 110.5, 119.9, 123.4, 123.7, 127.9, 128.5,
128.7, 130.0, 130.5 (all CH), 133.0, 136.8, 138.1, 143.2,
147.8 (all C) ppm; LR EI-MS: m/z (%) = 276 (M?, 100),
275 (63); HR EI-MS calcd for C17H12N2S, 276.0722 (M)?,
found 276.0717.
ꢀ
EtOAc, 7:3); mp 126–128 °C; IR (nujol): m = 1692, 1600,
1
1328, 1255, 1175, 1029, 830, 751, 704 cm-1; H NMR
(500 MHz, CDCl3): d = 3.78 (s, 3H), 6.81 (d, J = 9 Hz,
2H), 7.20–7.24 (m, 1H), 7.22 (d, J = 8 Hz, 1H), 7.29–7.34
(m, 3H), 7.43–7.52 (m, 3H), 7.50 (d, J = 9 Hz, 2H), 7.86
(d, J = 8 Hz, 1H) ppm; 13C NMR (125 MHz): d = 55.6
(CH3), 110.6, 114.1, 119.9, 123.2, 123.3, 127.9, 128.8,
130.2, 131.3 (all CH), 122.7, 137.64, 137.66, 143.4, 152.8,
160.9 (all C) ppm; LR EI-MS: m/z (%) = 300 (M?, 100),
123

380
M. Chakrabarty et al.
21. Tagawa Y, Yamagata K, Sumoto K (2008) Heterocycles 75:415
(Activated C–O2/xylenes)
22. Bahrami K, Khodaei MM, Kavianinia I (2007) Synthesis:547
(H2O2–HCl)
23. Du L-H, Wang Y-G (2007) Synthesis:675 (IBD)
24. Das B, Holla H, Srinivas Y (2007) Tetrahedron Lett 48:61
(Me2S?BrBr-)
25. Varala R, Nasreen A, Enugala R, Adapa SR (2007) Tetrahedron
Lett 48:69 (L-Proline–CHCl3)
26. Ma H, Wang Y, Li J, Wang J (2007) Heterocycles 71:135 (Ionic
liquid)
27. Nagawade RR, Shinde DB (2007) Indian J Chem 46B:349
(TiCl4)
28. Ramachary DB, Reddy GB (2006) Org Biomol Chem 4:4463
(L-Proline–EtOH)
2-Ethyl-1-phenylbenzimidazole (6, C15H14N2)
Oil (0.177 g, 80%) (Ref. [53] 45 °C); Rf = 0.6 (PE-EtOAc,
ꢀ
7:3); IR (neat): m = 1613, 1596, 1520, 1499, 1455, 1398,
1
1275, 1228, 1189, 1070, 1020, 743, 704 cm-1; H NMR
(500 MHz, CDCl3): d = 1.35 (t, J = 7.5 Hz, 3H), 2.81
(q, J = 7.5 Hz, 2H), 7.09 (d, J = 8 Hz, 1H), 7.18
(dt, J1 = 8 Hz, J2 = 1 Hz, 1H), 7.26 (dt, J1 = 7.5 Hz,
J2 = 1 Hz, 1H), 7.33–7.39 (m, 2H), 7.52 (tt, J1 = 7.5 Hz,
J2 = 1 Hz, 1H), 7.58 (t, J = 7.5 Hz, 2H), 7.79 (d, J = 8 Hz,
1H) ppm; 13C NMR (125 MHz): d = 12.4 (CH3), 21.6
(CH2), 110.3, 119.5, 122.7, 122.9, 127.7, 129.2, 130.3 (all
CH), 136.4, 137.0, 142.9, 156.6 (all C) ppm.
29. Ma H, Wang Y, Wang J (2006) Heterocycles 68:1669 (KHSO4)
30. Lin S, Yang L (2005) Tetrahedron Lett 46:4315 (Dioxane-air)
31. Curini M, Epifano F, Montanari F, Rosati O, Taccone S (2004)
Synlett:1832 (Yb(OTf)3)
32. Itoh T, Nagata K, Ishikawa H, Ohsawa A (2004) Heterocycles
63:2769 (Sc(OTf)3)
Acknowledgments We sincerely thank Professor S. Raha, the
Director, Bose Institute for laboratory facilities, the C.S.I.R., Gov-
ernment of India for providing a fellowship (S.K.), Mr. B. Majumder,
NMR Facilities and Mr. P. Dey, Microanalytical Laboratory, both of
the Bose Institute, for recording the spectra.
33. Nagata K, Itoh T, Ishikawa H, Ohsawa A (2003) Heterocycles
61:93 (Sc(OTf)3)
´
34. Beaulieu PL, Hache B, von Moos E (2003) Synthesis:1683
(OxoneÒ)
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