Hypervalent iodine mediated oxidation of 1,2-diaminobenzimidazole and its schiff bases: Efficient synthesis of 3-amino-1,2,4-benzotriazine and 2-aryl-1,2,4-triazolo[1,5-a]benzimidazoles

Article abstract of DOI:10.1055/s-0028-1088055

Hypervalent iodine mediated oxidation of 1,2-diaminobenzimidazole and its Schiff bases is described. The reaction produces 3-amino-1,2,4-benzotriazine and 2-aryl-1,2,4-triazolo[1,5-a]benzimidazoles efficiently. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088055

PAPER
1663
Hypervalent Iodine Mediated Oxidation of 1,2-Diaminobenzimidazole and Its
Schiff Bases: Efficient Synthesis of 3-Amino-1,2,4-benzotriazine and 2-Aryl-
1,2,4-triazolo[1,5-a]benzimidazoles
O
xidation of 1,2-D
s
iaminobe
h
nzimidazole
o
and Its Schif
k
f
B
ase
s
Kumar, Mahavir Parshad, Rakesh K. Gupta, Devinder Kumar*
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar 125001, Haryana, India
Fax +91(01662)276240; E-mail: dk_ic@yahoo.com
Received 6 January 2009; revised 23 January 2009
Oxidation of 1,2-Diaminobenzimidazole with Hyper-
valent Iodine Reagents
Abstract: Hypervalent iodine mediated oxidation of 1,2-diami-
nobenzimidazole and its Schiff bases is described. The reaction pro-
duces 3-amino-1,2,4-benzotriazine and 2-aryl-1,2,4-triazolo[1,5-
a]benzimidazoles efficiently.
1,2-Diaminobenzimidazole (1), which was needed in the
present study, was prepared from 2-aminobenzimidazole
Key words: hypervalent iodine reagents , 1,2-diaminobenzimida- and hydroxylamine-O-sulphonic acid. 1,2-Diaminobenz-
zole, 1,2,4-benzotriazine, 2-aryl-1,2,4-triazolo[1,5-a]benzimida-
zoles
imidazole (1), on stirring with iodobenzene diacetate
[PhI(OAc)2] or polymer-supported iodobenzene diacetate
(PSIBD) at 25 °C, efficiently afforded 3-amino-1,2,4-
benzotriazine (3) exclusively in 80% yield via ring expan-
Hypervalent iodine compounds have gained much signif-
icance in view of their versatile applications and diverse
chemical behavior in organic synthesis.1 In the recent
past, there has been much research in the field of nitrogen
heterocycles. 1,2-Diaminobenzimidazole and its deriva-
tives are biologically important molecules and reactions
with these molecules have generated a wide variety of het-
erocycles.2 1,2-Diaminobenzimidazoles have been shown
to be potential antimalarial agents3 as well as selective in-
hibitors of nitric oxide synthase.4
sion of the imidazole nucleus (Scheme 1). The most prob-
able mechanism for the ring expansion is best rationalized
via the intermediacy of nitrene 2, generated by the initial
attack of the 1-amino nitrogen on the electron-deficient
iodine(III) reagent. The nitrene, so generated, inserts into
the C–N bond to furnish 3. The benzotriazine was purified
by column chromatography over silica gel (60–120 mesh)
using hexane–ethyl acetate (4:1) as eluent.
N
N
N
PhI(OAc)2
CH2Cl2
NH2
NH2
3-Amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine,
TPZ), one of the most promising prodrugs, is currently in
phase II and III clinical trials.5 A series of 3-amino-1,2,4-
benzotriazine-1,4-dioxide derivatives that has recently
been synthesized even show more hypotoxic-cytotoxic
activity than TPZ itself.6 Recently, [7-(2,6-dichlorophe-
nyl)-5-methylbenzo[1,2,4]triazi-3-yl]-[4-(2-pyrrolidin-1-
ylethoxy)phenyl]amine, which is a potent orally active
Src inhibitor with desirable pK properties, demonstrated
activity in human tumor cell lines and in animal models of
tumor growth.7 Similarly, triazolo[1,5-a]benzimidazoles,
derived from 1,2-diaminobenzimidazole, have been found
to possess antifungal, anti-inflammatory and analgesic8 as
well as anti-histamine effects.9 Bearing in mind the bio-
logical importance of 1,2,4-benzotriazines and 2-aryl-
1,2,4-triazolo[1,5-a]benzimidazoles, it was thought to be
of interest to provide an efficient synthesis of these mole-
cules by the oxidation of 1,2-diaminobenzimidazole and
its Schiff bases utilizing hypervalent iodine reagents.
N
NH2
N
1
2
••
NH2OSO3H
N
N
N
N
NH2
N
NH2
H
3 80%
Scheme 1
The structure of the benzotriazine was established by
physical and spectroscopic techniques. The IR spectrum
of the 3-amino-1,2,4-benzotriazine displays two broad ab-
sorptions at 3280 cm–1 and 3148 cm–1, due to the NH2
1
group, in addition to other bands. In the H NMR spec-
trum, the NH2 protons appear at d = 5.60 ppm as a broad
singlet, the H-6 and H-7 protons resonate at d = 7.78 and
7.50 ppm, respectively, the H-5 proton appears as doublet
at d = 7.62 ppm (J = 8.4 Hz), while the H-8 proton reso-
nates as doublet of doublets at d = 8.31 ppm (J = 8.4, 1.2
Hz).
Oxidation of 1,2-diaminobenzimidazole with either
PhI(OAc)2 or PSIBD is a simple and efficient method of
preparing 3-amino-1,2,4-benzotriazine (3) and illustrates
the versatility of hypervalent iodine reagents in the oxida-
SYNTHESIS 2009, No. 10, pp 1663–1666
Advanced online publication: 20.04.2009
DOI: 10.1055/s-0028-1088055; Art ID: Z00209SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9

1664
A. Kumar et al.
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tion of N-amino compounds. Furthermore, the obtained 3- trum of 5a showed absorption bands at 3038 cm–1 due to
amino-1,2,4-benzotriazine can be employed as a precur- N–H stretching and at 1679 cm–1 and 1589 cm–1 due to
sor for synthesizing 3-amino-1,2,4-benzotriazine-1,4-ox- C=N stretching, in addition to other bands. The structure
ides (TPZ).6 This method offers many advantages over of 5a was established through NMR (1H, 13C) and 2D
similar oxidation reactions with 1,2-diaminobenzimida- NMR. The HRMS and fragmentation pattern of 5b was in
zoles using lead(IV) acetate10 or manganese dioxide,11 to complete agreement with the structure.
afford 3-amino-1,2,4-benzotriazines.
Oxidation of 2-Amino-N1-(arylideneamino)benzimi- involves initial electrophilic attack of either PhI(OAc)2 or
A plausible mechanistic pathway for the formation of 5
dazoles with Hypervalent Iodine Reagents
PSIBD on the C=N bond of 4, with simultaneous intramo-
lecular nucleophilic participation of the 2-amino group,
resulting in cyclic adduct 6. Reductive elimination of the
iodobenzene or iodopolystyrene, in addition to acetic
acid, furnished 5 (Scheme 3).
2-Amino-1-(arylideneamino)benzimidazoles
(Schiff
bases, 4) were obtained regioselectively from 1 and aryl-
aldehydes in ethanol, in 76–81% yield (Scheme 2). The
regioselective formation of 4 may be attributed to the
greater nucleophilicity of the 1-amino nitrogen as com-
pared to the 2-amino nitrogen. The structure of Schiff
bases was established by physical and spectroscopic tech-
N
N
PhI(OAc)2
NH2
NH2
CH2Cl2, AcOH
N
N
1
niques (IR, H and 13C NMR and HRMS). The IR spec-
N
N
CH Ar
CH Ar
4
trum of the Schiff bases displayed two broad absorption
bands at 3445 15 cm–1 and 3050 20 cm–1, corresponding
OAc
OAc
Ph
I
1
to the NH2 group, in addition to other bands. In the H
– OAc–
NMR spectrum of 4b, the methoxy protons resonate at
d = 3.88 ppm, while the NH2 protons appeared as a broad
singlet. The methine proton was found as singlet at d =
8.88 ppm, in addition to other signals (see experimental).
As expected, the molecular ion of 4b was found at m/z =
266.1171 (71%) in the HRMS. The characteristic frag-
mentation involves cleavage of the N–N bond to produce
the 2-aminobenzimidazole radical cation [m/z = 132.0568
(100%)] as the base peak.
H
N
H
N
– PhI, AcOH
N
N
N
N
H
N
N
Ar
Ar
I
Ph
5
OAc
Scheme 3
Although 2-aryl-1,2,4-triazolo[1,5-a]benzimidazoles (5)
may exist in three tautomeric forms (1H, 3H and 4H),
NMR data revealed that it exists mostly in the 4H form
(Figure 1). This observation has found support from a
similar study that established the position of the tautomer-
ic equilibrium by means of a number of physicochemical
methods in conjunction with quantum-mechanical calcu-
lations and alkylation data.12 The relative amount of the
4H tautomer in the equilibrium mixture was two to three
orders of magnitude greater than the amount of 3H tau-
tomer, while no evidence for the existence of the 1H form
was found.
N
N
ArCHO, EtOH, AcOH
reflux, 10–12 h
NH2
NH2
N
N
NH2
N
CH Ar
1
4 76–81%
PhI(OAc)2
CH2Cl2
H
N
a Ar = 4-MeC6H4
b Ar = 4-MeOC6H4
c Ar = 4-ClC6H4
d Ar = 4-BrC6H4
3
+
N
N
N
Ar
5
Scheme 2
H
N
N
N
N
N
Oxidation of 4 with either PhI(OAc)2 or PSIBD in dichlo-
romethane at 25 °C resulted in the formation of 2-aryl-
1,2,4-triazolo[1,5-a]benzimidazoles (5) in 48–57% yield,
along with minor amounts (18–25%) of 3-amino-1,2,4-
benzotriazine (3). The formation of 4 may be explained by
the intramolecular participation of the 1-amino group,
while 3 is probably formed due to partial cleavage of the
Schiff base to generate the 1,2-diaminobenzimidazole (1),
which is then available for further oxidation. The products
were separated by column chromatography over silica gel
(60–120 mesh) using hexane–ethyl acetate as eluent.
N
NH
N
N
N
N
N
Ar
Ar
Ar
H
3H
1H
4H
Figure 1
A number of reports describe the synthesis of 2-aryl-
1,2,4-triazolo[1,5-a]benzimidazoles (5), for example, py-
rolysis of 1-(2-benzimidazolyl)-5-1H-tetrazoles13 and
from the reaction of 1,2-diaminobenzimidazole with car-
boxylic anhydrides14,15 or formamides.16 However, al-
though compound 5 could not be obtained by the
cyclization of 4 using copper(II) acetate monohydrate,10
The structure of 2-aryl-1,2,4-triazolo[1,5-a]benzimida-
zoles (5) was established using physical and spectroscopic
techniques (IR, NMR, HRMS). In particular, the IR spec-
Synthesis 2009, No. 10, 1663–1666 © Thieme Stuttgart · New York

PAPER
Oxidation of 1,2-Diaminobenzimidazole and Its Schiff Bases
1665
Synthesis of Schiff Bases of 1,2-Diaminobenzimidazole; Gener-
al Procedure
2-methylamino-1-arylidenebenzimidazoles were convert-
ed into the corresponding triazolo[1,5-a]benzimidazoles
on refluxing in nitrobenzene (20–30% yield), along with
trace amounts of 2-methylaminobenzimidazole and aryl
nitriles.17 Biologically active 1-acyl-2-alkylthio-1,2,4-tri-
azolo[2,3-a]benzimidazoles were also synthesized by the
reaction of 1,2-diaminobenzimidazole with carbon disul-
fide in dimethyl formamide, followed by reaction with
one equivalent of alkyl halide to give the corresponding 2-
alkylthio-1,2,4-triazolo[2,3-a]benzimidazole and acyla-
tion with various acyl halides.8 In the present study the re-
action has been generalized and involves simple and
efficient experimental techniques that result in good
yields of pure product.
Appropriate aromatic aldehyde (10 mmol) was added to a solution
of 1,2-diaminobenzimidazole (1; 1.48 g, 10 mmol) in anhydrous
EtOH (20 mL) containing 3–4 drops of glacial AcOH. The resulting
solution was refluxed for 10–12 h on a heating mantle. The solid ob-
tained on cooling was collected at suction, washed with H2O (3 × 10
mL) and recrystallized form aq EtOH to afford the pure Schiff
bases.
2-Amino-N1-(4-methylbenzylideneamino)benzimidazole (4a)
Yield: 79%; mp 231–232 °C.
IR (KBr): 3441, 3079, 1659, 1611, 1551, 1491, 1439, 1412, 1354,
1302, 1265, 1139, 865, 729 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 2.42 (s, 3 H, CH3), 5.96 (br s,
2 H, NH2), 7.05 (dt, J = 1.4, 7.6 Hz, 1 H, 6-H), 7.13 (dt, J = 0.7, 7.7
Hz, 1 H, H-5), 7.29 (d, J = 7.9 Hz, 2 H, H-3¢, H-5¢), 7.37 (d, J = 7.5
Hz, 1 H, H-4), 7.60 (d, J = 7.8 Hz, 1 H, H-7), 7.79 (d, J = 8.0 Hz,
2 H, H-2¢, H-6¢), 8.89 (s, 1 H, N=CH).
13C NMR (CDCl3 + DMSO-d6): d = 21.02 (CH3), 109.3, 116.3,
119.3, 122.0, 127.0, 129.0, 130.4, 140.8, 141.2, 147.8, 153.2.
In conclusion, we have found that hypervalent iodine me-
diated oxidative reaction of 1,2-diaminobenzimidazole
(1) led to the efficient synthesis of 3-amino-1,2,4-benzo-
triazines (3), whereas 2-amino-1-(arylideneamino)benz-
imidazoles (Schiff bases, 4) produced 2-aryl-1,2,4-
triazolo[1,5-a]benzimidazoles (5) in 48–57% yield. All
the reactions were also carried out using 2% cross-linked
HRMS: m/z (%) calcd for C15H14N4: 250.1218; found: 250.1215
(59), 249.1141 (19), 133.0630 (26), 132.0565 (100), 105.0442 (38),
polystyrene-supported (diacetoxyiodo)benzene (PSDIB). 90.0342 (14).
It was found that the reactivity, reaction time and yields of
2-Amino-N1-(4-methoxybenzylideneamino)benzimidazole (4b)
Yield: 76%; mp 213–214 °C.
both approaches were comparable. However, the advan-
tage of using PSDIB was that iodopolystyrene generated
during the reaction could be filtered off and recycled to
PSDIB for further use.
IR (KBr): 3437, 3024, 1660, 1606, 1552, 1514, 1481, 1452, 1417,
1359, 1303, 1255, 1168, 1028, 829, 719 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 3.88 (s, 3 H, OCH3), 5.86 (br s,
2 H, NH2), 7.00 (d, J = 8.0 Hz, 2 H, H-3¢, H-5¢), 7.05 (dt, J = 0.8,
7.6 Hz, 1 H, H-6), 7.13 (dt, J = 0.9, 7.6 Hz, 1 H, H-5), 7.37 (d,
J = 7.5 Hz, 1 H, H-4), 7.59 (d, J = 7.8 Hz, 1 H, H-7), 7.83 (d, J = 8.8
Hz, 2 H, H-2¢, H-6¢), 8.88 (s, 1 H, N=CH).
13C NMR (CDCl3 + DMSO-d6): d = 54.8 (OCH3), 109.1, 113.7,
116.3, 119.2, 121.8, 125.6, 128.7, 129.0, 141.2, 148.0, 153.0, 161.3.
Melting points were determined in open capillaries and are uncor-
rected. FTIR spectra were obtained in KBr on either Shimadzu
FTIR 8210 PC or Perkin–Elmer Spectrum RX1 instruments and are
1
reported in cm–1. H and 13C NMR spectra were determined on a
Bruker Avance II NMR spectrometer operating at 400 MHz and
100 MHz, respectively, in CDCl3 or CDCl3 + DMSO-d6 and are ex-
pressed in ppm with respect to TMS. 2D-NMR spectra were
scanned on a Bruker Avance II NMR spectrometer. Elemental anal-
ysis was carried out on a Perkin–Elmer 2400 instrument. HRMS
were recorded on a VG 70 EB mass spectrometer and accurate mass
measurements were made on a PE-Biosystems Mariner ESI-TOF
mass spectrometer. All solvents were dried using standard proce-
dures.
HRMS: m/z (%) calcd for C15H14N4O: 266.1167; found: 266.1171
(71), 265.1090 (18), 133.0629 (51), 132.0568 (100), 105.0461 (40),
90.0344 (23).
2-Amino-N1-(4-chlorobenzylideneamino)benzimidazole (4c)
Yield: 81%; mp 210–211 °C.
IR (KBr): 3452, 3091, 1653, 1601, 1593, 1538, 1449, 1375, 1281,
1068, 1011, 819, 742 cm–1.
Oxidation of 1,2-Diaminobenzimidazole (1) to 3-Amino-1,2,4-
benzotriazine (3) Using Iodobenzene Diacetate
1H NMR (CDCl3 + DMSO-d6): d = 6.02 (br s, 2 H, NH2), 7.06 (t,
J = 7.0, 7.4 Hz, 1 H, H-6), 7.15 (t, J = 7.2, 7.6 Hz, 1 H, H-5), 7.38
(d, J = 8.1 Hz, 1 H, H-4), 7.45 (d, J = 8.4 Hz, 2 H, H-3, H-5), 7.61
(d, J = 7.8 Hz, 1 H, H-7), 7.85 (d, J = 7.8 Hz, 2 H, H-2¢, H-6¢), 8.98
(s, 1 H, N=CH).
13C NMR (CDCl3 + DMSO-d6): d = 109.5, 116.3, 119.5, 122.4,
128.2, 128.5, 128.8, 131.8, 136.0, 141.1, 145.8, 153.1.
Iodobenzene diacetate (708 mg, 2.2 mmol) was added to a suspen-
sion of 1,2-diaminobenzimidazole (1; 296 mg, 2 mmol) in CH2Cl2
(10 mL), and the resulting mixture was stirred at 25 °C for 40 min
(TLC indicated the reaction was complete). Excess solvent was re-
moved under reduced pressure at low temperature and the crude,
gummy mass was purified by percolating through a short column of
silica gel (60–120 mesh; hexane–EtOAc, 4:1) to afford the yellow-
ish benzotriazine.
Yield: 80%; mp 206–207 °C (Lit.10 206 °C).
IR (KBr): 3235, 3090, 1665, 1545, 1201, 987, 764 cm–1.
1H NMR (CDCl3): d = 5.60 (br s, 2 H, NH2), 7.50 (dd, J = 1.2, 7.6
Hz, 1 H, H-7), 7.62 (d, J = 8.4 Hz, 1 H, H-5), 7.78 (dd, J = 1.4, 7.7
Hz, 1 H, H-6), 8.31 (dd, J = 1.2, 8.4 Hz, 1 H, H-8).
HRMS: m/z (%) calcd for C14H11ClN4: 272.0642, 270.0672; found:
272.0633 (13), 270.0662 (35), 133.0623 (23), 132.0569 (100),
105.0395 (38), 90.0345 (23).
2-Amino-N1-(4-bromobenzylideneamino)benzimidazole (4d)
Yield: 80%; mp 224–225 °C.
IR (KBr): 3460, 3068, 1656, 1612, 1589, 1550, 1454, 1365, 1299,
1278, 1247, 1066, 1008, 817, 734 cm–1.
1H NMR (CDCl3 + DMSO-d6): d = 5.99 (br s, 2 H, NH2), 7.06 (t,
J = 7.3, 8.0 Hz, 1 H, H-6), 7.15 (t, J = 7.2, 8.0 Hz, 1 H, H-5), 7.37
Synthesis 2009, No. 10, 1663–1666 © Thieme Stuttgart · New York

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A. Kumar et al.
PAPER
(d, J = 7.6 Hz, 1 H, H-4), 7.60–7.64 (m, 3 H, H-3¢, H-5¢, H-7), 7.80
(d, J = 8.4 Hz, 2 H, H-2, H-6), 8.89 (s, 1 H, N=CH).
IR (KBr): 3401, 2927, 1585, 1488, 1466, 1388, 1325, 1278, 1165,
1066, 1002, 763, 725 cm–1.
13C NMR (CDCl3 + DMSO-d6): d = 109.5, 116.4, 119.4, 122.3,
1H NMR (CDCl3): d = 7.70 (d, J = 8.6 Hz, 2 H, H-3¢, H-5¢), 7.86 (t,
J = 1.2, 6.8 Hz, 1 H, H-7), 7.96–7.98 (m, 1 H, H-6), 8.08 (d, J = 8.5
Hz, 1 H, H-5), 8.54 (d, J = 8.44 Hz, 1 H, H-8), 8.64 (dd, J = 2.1,
9.28 Hz, 2 H, H-2¢, H-6¢).
13C NMR (CDCl3): d = 126.5, 129.1, 129.6, 130.3, 130.5, 132.2,
134.5, 135.8, 141.0, 146.5, 159.0.
124.4, 128.4, 128.9, 131.4, 132.2, 141.4, 145.6, 153.2.
HRMS: m/z (%) calcd for C14H11BrN4: 316.0146, 314.0167; found:
316.0148 (21), 314.0178 (22), 133.0611 (23), 132.0551 (100),
105.0442 (38), 90.0357 (22).
Oxidation of Schiff Bases to Triazolo[1,5-a]benzimidazoles (5)
and 3-Amino-1,2,4-benzotriazine (3); General Procedure
Iodobenzene diacetate (1.42 g, 4.2 mmol) was added to a suspen-
sion of the appropriate Schiff base (4 mmol) in CH2Cl2 (15 mL),
whereupon the Schiff base started to dissolve and the reaction mix-
ture became dark-brown. The reaction was stirred for 1 h at 25 °C,
then excess solvent was removed under reduced pressure. The gum-
my mass, so obtained, was adsorbed on silica gel (60–120 mesh)
and purified by chromatography (silica gel; hexane–EtOAc,
9:1→95:5) to isolate first 3-amino-1,2,4-benzotriazine (3) followed
by triazolo[1,5-a]benzimidazoles (5).
HRMS: m/z (%) calcd for C14H9N4Br: 312.0011; found: 312.0003
(100) [M+].
Acknowledgment
The authors are thankful to the University Grants Commission,
New Delhi for financial support to Mr. Ashok Kumar (SRF). We
also appreciate Mr. Avtar Singh of Panjab University, Chandigarh
for recording NMR spectra efficiently. The mass spectrometry faci-
lity, University of California, USA is highly acknowledged for
HRMS data.
2-(Methylphenyl)-1,2,4-triazolo[1,5-a]benzimidazole (5a)
Yield: 56%; mp 116–117 °C (Lit.13 330–331 °C).
References
IR (KBr): 3314, 2927, 1606, 1560, 1504, 1448, 1394, 1328, 1236,
1103, 1010, 835, 763 cm–1.
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1H NMR (CDCl3): d = 2.47 (s, 3 H, CH3), 7.39 (d, J = 8.0 Hz, 2 H,
H-3¢, H-5¢), 7.78–7.82 (m, 1 H, H-7), 7.92–7.96 (m, 1 H, H-6), 8.07
(d, J = 8.2 Hz, 1 H, H-5), 8.51 (dd, J = 0.7, 8.4 Hz, 1 H, H-8), 8.65
(d, J = 8.2 Hz, 2 H, H-2, H-6).
13C NMR (CDCl3): d = 21.68 (CH3), 128.7, 129.1, 129.3, 129.6,
129.8, 129.9, 132.9, 135.4, 141.1, 141.9, 146.4, 159.9.
HRMS: m/z (%) calcd for C15H12N4: 248.1062; found: 248.1079
(100) [M+].
2-(Methoxyphenyl)-1,2,4-triazolo[1,5-a]benzimidazole (5b)
Yield: 48%; mp 133–134 °C (Lit. 320–322 °C,13 168–170 °C18).
IR (KBr): 3398, 3023, 2890, 1584, 1501, 1388, 1285, 1225, 1091,
845, 735 cm–1.
1H NMR (CDCl3): d = 3.92 (s, 3 H, OCH3), 7.09 (d, J = 8.9 Hz, 2 H,
H-3, H-5), 7.76–7.78 (m, 1 H, H-7), 7.93 (dt, J = 1.2, 8.4 Hz, 1 H,
H-6), 8.04 (d, J = 8.4 Hz, 1 H, H-5), 8.49 (d, J = 8.3 Hz, 1 H, H-5),
8.73 (d, J = 8.8 Hz, 2 H, H-2¢, H-6¢).
(7) Rosowsky, A.; Forsch, R. A.; Moran, R. G. Bioorg. Med.
Chem. Lett. 2007, 17, 602.
(8) Mohamed, B. G.; Abdel-Alim, A. M.; Hussein, M. A. Acta
Pharm. 2006, 56, 31.
(9) Spasov, A. A.; Chernikov, M. V.; Anisimova, V. A.;
Kuz’menko, T. A. Pharm. Chem. J. 2000, 34, 48.
(10) (a) Zeiger, A. V.; Joullie, M. M. J. Org. Chem. 1977, 42,
542. (b) Zeiger, A. V.; Joullie, M. M. Synth. Commun. 1976,
6, 457.
13C NMR (CDCl3): d = 55.5 (OCH3), 114.4, 128.3, 129.0, 129.6,
130.5, 135.4, 141.4, 141.2, 146.2, 159.7, 162.5.
HRMS: m/z (%) calcd for C14H12N4O: 264.1011; found: 264.1003
(23) [M+], 237.0924 (76), 209.0843 (100), 166.0655 (36), 103.0422
(22), 90.0347 (33).
(11) Nakajima, M.; Hisada, R.; Anselma, I.-P. J. Org. Chem.
1979, 43, 2693.
(12) Kuz’menko, V. V.; Kuz’menko, T. A.; Pozharskii, A. F.;
Dorron’kin, V. N.; Chikina, N. L.; Pozharskaya, S. S. Chem.
Heterocycl. Compd. 1989, 168.
(13) Rao, P. J.; Reddy, K. K. Synth. Commun. 1988, 18, 1995.
(14) Ho, R. I.-F.; Day, A. R. J. Org. Chem. 1973, 38, 3084.
(15) Tamura, Y.; Hayashi, H.; Kim, J.-H.; Ikeda, M. Chem.
Pharm. Bull. 1979, 27, 2521.
(16) Kuz’menko, V. V.; Kuz’menko, T. A.; Simonov, A. M.
Chem. Heterocycl. Compd. 1987, 235.
2-(Chlorophenyl)-1,2,4-triazolo[1,5-a]benzimidazole (5c)
Yield: 55%; mp 142–143 °C (Lit.13 339–340 °C).
IR (KBr): 3442, 3038, 2852, 1667, 1589, 1498, 1390, 1240, 1089,
1006, 836, 764 cm–1.
1H NMR (CDCl3): d = 7.56 (d, J = 8.6 Hz, 2 H, H-3¢, H-5¢), 7.86–
7.89 (m, 1 H, H-7), 7.99 (t, J = 6.9, 7.8 Hz, 1 H, H-6), 8.09 (d,
J = 8.4 Hz, 1 H, H-5), 8.54 (d, J = 8.3 Hz, 1 H, H-8), 8.72 (d, J = 8.6
Hz, 2 H, H-2¢, H-6¢).
13C NMR (CDCl3): d = 129.1, 129.3, 129.7, 130.1, 130.5, 134.1,
135.8, 137.9, 141.0, 146.5, 159.0. HRMS: m/z (%) calcd for
C14H9N4Cl: 268.0516; found: 268.0471 (100) [M+].
(17) Kuz’menko, T. A.; Kuz’menko, V. V.; Pozharshii, A. F.;
Klynev, N. A. Chem. Heterocycl. Compd. 1989, 1012.
(18) Reddy, B. S.; Sambaiah, T.; Reddy, K. K. Indian J. Chem.,
Sect. B: Org. Chem. Incl. Med. Chem. 1992, 31, 191.
2-(Bromophenyl)-1,2,4-triazolo[1,5-a]benzimidazole (5d)
Yield: 57%; mp 138–139 °C.
Synthesis 2009, No. 10, 1663–1666 © Thieme Stuttgart · New York