2-aryl(hetaryl)-4H-[1,2,4]triazolo[1,5-a]benzimidazoles

Article abstract of DOI:10.1134/S107042801306016X

2-(4-Methylphenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole and its previously unknown 2-(2-furyl)- and 2-(2-thienyl)-substituted analogs were synthesized by cyclization of benzimidazole-1,2-diamine with the corresponding carboxylic acid chlorides. The IR, ¹H, ¹³C, and ¹⁵N NMR, and mass spectra of the cyclization products in combination with the results of quantum-chemical calculations of NMR chemical shifts showed radical differences of [1,2,4]triazolo[1,5-a]benzimidazoles having no substituent on N⁴ from the recently reported low-melting products of oxidation of 2-amino-1-arylmethylideneaminobenzimidazoles with (diacetoxy-λ³-iodanyl)benzene, which, as we believe, were erroneously assigned analogous structure.

Full text of DOI:10.1134/S107042801306016X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 6, pp. 895–903. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.S. Morkovnik, T.A. Kuz’menko, L.N. Divaeva, G.S. Borodkin, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49,
No. 6, pp. 909–917.
2-Aryl(hetaryl)-4H-[1,2,4]triazolo[1,5-a]benzimidazoles
A. S. Morkovnik, T. A. Kuz’menko, L. N. Divaeva, and G. S. Borodkin
Research Institute of Physical and Organic Chemistry, Southern Federal University,
pr. Stachki 194/2, Rostov-on-Don, 344090, Russia
e-mail: asmork2@ipoc.rsu.ru
Received September 19, 2012
Abstract—2-(4-Methylphenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole and its previously unknown
2-(2-furyl)- and 2-(2-thienyl)-substituted analogs were synthesized by cyclization of benzimidazole-1,2-di-
amine with the corresponding carboxylic acid chlorides. The IR, 1H, 13C, and 15N NMR, and mass spectra of the
cyclization products in combination with the results of quantum-chemical calculations of NMR chemical shifts
showed radical differences of [1,2,4]triazolo[1,5-a]benzimidazoles having no substituent on N4 from the
recently reported low-melting products of oxidation of 2-amino-1-arylmethylideneaminobenzimidazoles with
(diacetoxy-λ3-iodanyl)benzene, which, as we believe, were erroneously assigned analogous structure.
DOI: 10.1134/S107042801306016X
Kumar et al. [1] recently reported on the oxidation
of 2-amino-1-(arylmethylideneamino)benzimidazoles
with (diacetoxy-λ3-iodanyl)benzene; the oxidation
products were assigned the structure of 2-aryl[1,2,4]-
triazolo[1,5-a]benzimidazoles Ia–Id on the basis of
their IR, 1H and 13C NMR, and mass spectra.
are high-melting substances, which may be due to their
ability to form H-dimers [9].
Nevertheless, despite citing the data of [2–4], no
comments were given in [1] on so evident inconsis-
tency between the most important physical character-
istic of the synthesized compounds and those of known
analogs. The present communication is anticipated to
clarify the problem which properties are in fact in-
trinsic to triazolobenzimidazoles I.
N1
R
8
9N
2
8a
7
N3
3a
4
For this purpose, we synthesized 2-(4-methylphe-
nyl)[1,2,4]triazolo[1,5-a]benzimidazole (Ia), which
was differently characterized in [1, 2], by an independ-
ent method, cyclization of diamine II with p-toluoyl
chloride. This reaction, as well as the reaction with
carboxylic acid anhydrides [4], is likely to involve
intermediate formation of quaternary salt A, since the
primary product was 4-acyl derivative III (Scheme 1).
The subsequent hydrolysis of III gave the correspond-
ing N-unsubstituted triazolobenzimidazole Ia with
mp 317–318°C, which is consistent with the data of
[2]. Unlike low-melting compound described in [1],
which was readily soluble in chloroform and in hex-
ane–ethyl acetate (9:1), the cyclization product synthe-
sized by us was poorly soluble in most organic sol-
vents and was purified by recrystallization from DMF.
6
4a
N
5
H
Ia–Id
R = 4-MeC6H4 (a), 4-MeOC6H4 (b), 4-ClC6H4 (c),
4-BrC6H4 (d).
However, these compounds had unexpectedly low
melting points (116–143°C, depending on the aryl
substituent [1]), which were lower by approximately
200°C than those of structurally identical compounds
obtained by pyrolysis of 2-tetrazolylbenzimidazoles
[2]. The parent compound of this series, [1,2,4]tri-
azolo[1,5-a]benzimidazole and its 2-methyl- and
2-phenyl-substituted derivatives [3, 4] synthesized by
cyclization of benzimidazole-1,2-diamine (II) with
carboxylic acid derivatives are characterized by fairly
high melting points. Furthermore, it is well known that
structurally related N-unsubstituted [1,2,4]triazolo-
[4,3-a]benzimidazoles [5], pyrazolo[1,5-a]benzimid-
azoles [6, 7], and imidazo[1,2-a]benzimidazoles [8]
With a view to extend the substrate series, by reac-
tion of diamine II with 2-furoyl and 2-thenoyl chlo-
rides we synthesized previously unknown 2-hetaryl
[1,2,4]triazolo[1,5-a]benzimidazoles Ie and If which
895

MORKOVNIK et al.
896
Scheme 1.
R
NH2
NHCOR
N
N
N
N
N
RCOCl
OH–
N
Ia
NH2
NH2
N
N
Cl–
COR
COR
III
II
A
R
N
(1) RCOCl
(2) OH–
MeI, OH–
N
N
N
II
Ie, If
Me
IVe, IVf
III, R = 4-MeC6H4; I, IV, R = 2-furyl (e), 2-thienyl (f).
also melted at high temperature and, like other tri-
azolo[1,5-a]benzimidazoles [4], were smoothly al-
kylated with methyl iodide in alkaline medium to
produce 4-methyl derivatives IVe and IVf.
Unfortunately, we failed to obtain crystals of I and
III suitable for X-ray analysis, and their structure was
studied by IR spectroscopy, mass spectrometry, and
one- and two-dimensional 1H, 13C, and 15N NMR tech-
niques. In order to interpret their NMR spectra, the 1H,
13C, and 15N chemical shifts of the 4H-tautomers
(which were shown [4] to dominate for triazolo[1,5-a]-
benzimidazoles) of Ia, acyl derivative III, and two
N9 209.9
1
Fig. 1. Experimental and calculated (in parentheses) H, 13C, and 15N NMR chemical shifts of 4-(4-methylbenzoyl)-2-(4-methyl-
phenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole (III).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

2-ARYL(HETARYL)-4H-[1,2,4]TRIAZOLO[1,5-a]BENZIMIDAZOLES
897
N9 (195.32)
V
N9 (222.77)
VI
Fig. 2. Calculated 1H, 13C, and 15N NMR chemical shifts of model 1- and 3-acyl-substituted 4H-[1,2,4]triazolo[1,5-a]benzimidazoles
V and VI.
model structures V and VI with an aroyl group on N1
compound was selected among those possible; in par-
ticular, such conformer of acyl derivative III was that
and N3 (Figs. 1–3) were calculated by the density
in which the 5-H proton is as close as possible to the
C=O group and is therefore deshielded to the strongest
extent.
The IR spectrum of N-acyl derivative III contains
a strong carbonyl stretching vibration band at
functional-based SOS DFPT method using IGLO-II
basis set [10] without considering solvent effects. The
geometric parameters were preliminarily optimized at
the DFT B3LYP/6-31G** level of theory. To simplify
the calculation procedure, only one conformer of each
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

MORKOVNIK et al.
898
N9 208.5 (225.0)
Fig. 3. Experimental and calculated (in parentheses) 1H, 13C, and 15N NMR chemical shifts of 2-(4-methylphenyl)-4H-[1,2,4]triazolo-
[1,5-a]benzimidazole (Ia).
1696 cm–1. No such band is present in the spectrum of
N-unsubstituted triazolobenzimidazole Ia, but a broad
band is observed in the region 2620–3017 cm–1 due to
stretching vibrations of the NH group. A signal assign-
able to the NH proton (δ ~12 ppm) was detected in the
1H NMR spectra of Ia, Ie, and If, whereas Kumar et al.
[1] noted the absence of NH signal in the NMR
spectra.
The 13C NMR spectrum of acyl derivative III
interpreted with account taken of the calculation data
and two-dimensional spectra contains 19 expected sig-
nals from carbon nuclei (or couples of carbon nuclei)
whose chemical shifts were as a rule lower by 2–4 ppm
than the calculated values (Fig. 1). The difference may
be attributed to errors of the calculation methods and
neglect of solvation effects. It was impossible to dis-
tinguish between the C6 and C7 signals at δC 125.11
and 125.14 ppm; due to insignificant difference in the
chemical shifts, common cross peaks with protons
were observed in the two-dimensional spectra, and
comparison of the experimental and calculated chemi-
cal shifts is rendered incorrect. The calculations also
predicted similarity of the chemical shifts of C6/C7 and
6-H/7-H in III; the corresponding differences Δδ
should be 0.09 and 0.05 ppm, respectively (Fig. 1).
The C2 and C=O carbon atoms (δC 163.99 and
165.92 ppm) which do not display cross-peaks with
protons in the 1H–13C HMBC spectrum were identified
only on the basis of the calculation data. The aromatic
carbons atoms in the two aryl substituents were
1
The H NMR spectrum of 4-(p-toluoyl) derivative
III (Fig. 1) is very similar to the spectrum of known
4-acetyl[1,2,4]triazolo[1,5-a]benzimidazole where the
position of the acetyl group was reliably determined
[4]. Multiplet signals from 6-H and 7-H in the spec-
trum of III (δ 7.54 and 7.51 ppm,* respectively) also
overlapped each other, and the 5-H and 8-H signals
were displaced downfield due to magnetic anisotropy
of the C=O group and N1 atom. According to the data
of two-dimensional NMR spectroscopy and quantum-
chemical calculations, the 5-H proton of III and 8-H in
I and IV should resonate in a weaker field.
The calculated chemical shifts of protons in com-
pound III differ from the corresponding experimental
values by ~0.1–0.2 ppm. Exceptions are 5-H and ortho
protons in the aryl and aroyl groups, for which δcalc
values are overestimated by 0.75, 0.48, and 0.33 ppm,
respectively. This may be related to specific features of
the selected conformer and slanting potential energy
surface of the molecule in the region corresponding to
rotation of the tolyl groups about C–C bonds.
1
1
assigned by analysis of the H–13C HMBC and H–1H
COSY spectra.
It was impossible to determine the position of the
acyl group in molecule III on the basis of two-
1
dimensional 13C–1H and H–1H NMR spectra because
of the lack of cross-peaks between nuclei in the acyl
group and triazolobenzimidazole system. Therefore,
the structure of III as 4-acyl derivative was confirmed
by comparing the experimental 1H, 13C, and 15N chem-
ical shifts with those calculated for structure III and
model structures V and VI where the acyl group is
* The 6-H and 7-H signals of III and I were identified taking into
account that these protons showed in the 15N–1H HMBC spectra
correlations with the 15N nuclei in the meta rather than para
position.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

2-ARYL(HETARYL)-4H-[1,2,4]TRIAZOLO[1,5-a]BENZIMIDAZOLES
899
7-H
Me
2′-H
3′-H
5-H
6-H
8-H
DMSO
H2O
δC, ppm
CMe
C
Me/CH3
24
40
56
72
88
104
C8/8-H
C8
C5
C7
C6
C5/5-H
C7/7-H
C2′/2′-H
C6/6-H
C2′
120
C3′
C3′/3′-H
8.0
7.0
6.0
5.0
4.0
3.0
δ, ppm
Fig. 4. Two-dimensional 1H–13C HSQC spectrum of 2-(4-methylphenyl)-4H-[1,2,4]triazolo[1,5-a]benzimidazole (Ia).
attached to N1 and N3, respectively (Fig. 2). In this
respect, the most indicative were the 15N NMR data for
N4. The N4 atom in 4-substituted triazolobenzimid-
azoles is sp3-hybridized, and in 1- and 3-substituted
derivatives, sp2-hybridized. As followed from the
15N–1H HMBC spectrum,** the chemical shift of N4 is
δN 149.0 ppm. This value is much closer to that calcu-
lated for structure III (δN 166.1 ppm) than to those
found for model 1- and 3-acyl-substituted isomers
(δN 234.1 and 209.9 ppm, respectively; Fig. 2). In this
case, the reduced accuracy of the calculations may be
rationalized by strong effect of solvation on the chemi-
cal shifts of nitrogen nuclei [11], which is untypical of
carbon nuclei.
ture of 1- or 3-(4-methylbenzoyl)-2-(4-methylphenyl)-
[1,2,4]triazolo[1,5-a]benzimidazole, is most likely to
be 4-acyl derivative III, for it is characterized by the
same melting point and almost identical IR and 1H and
13C NMR spectra.
Unlike 4-acyl derivative III, N-unsubstituted com-
pounds I displayed larger differences in the chemical
shifts of 6-H and 7-H and especially of C6 and C7; e.g.,
for Ia: Δδ(6-H/7-H) = 0.06, Δδ(C6/C7) = 2.57 ppm. In
this case, signals from 6-H and 7-H with similar multi-
plicities and spin–spin coupling constants, as well as
signals from C6 and C7, can be readily identified using
the two-dimensional HSQC (Fig. 4) and HMBC tech-
niques. The C4a/6-H cross-peak in the 13C–1H HMBC
spectrum was much more intense than the cross-peak
of C4a with more distant 7-H proton, and the 15N–1H
HMBC spectrum contained N4/6-H and N9/7-H cross
peaks, whereas neither N4/7-H nor N9/6-H coupling
was observed.
The cyclization product of 1,2-bis(triphenyl-λ5-
phosphanylideneamino)benzimidazole with p-toluoyl
chloride, which was assigned previously [12] the struc-
** The spectrum contained only signals of N4 and N9 whose cross-
peaks with protons were considerably stronger than those of
more distant N1 and N3 nuclei.
Comparison of the NMR spectra of triazolo[1,5-a]-
benzimidazoles I synthesized in the present work with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

MORKOVNIK et al.
900
the spectra of compounds described in [1] revealed
considerable differences in the spectral regions corre-
sponding directly to the heterocyclic system. The
1H NMR spectra of our samples lacked aromatic pro-
ton signals downfield from δ 7.9 ppm (Fig. 4), whereas
the compounds described in [1] displayed two signals
in the region δ 8.1–8.5 ppm, which were assigned to
5-H and 8-H. So strong downfield shift of signals from
protons in the benzimidazole fragment was observed
for neither known triazolobenzimidazoles [4, 12, 13]
nor structurally related 2-arylpyrazolo[1,5-a]benzimid-
azoles [7] and imidazo[1,2-a]benzimidazoles [9].
The chemical shifts of C5 and C8 in the compounds
under comparison were also considerably different.
According to the calculations, the C5 and C8 nuclei in
triazolo[1,5-a]benzimidazoles should experience en-
hanced shielding, and their signals should therefore be
shifted appreciably upfield. In particular, the calculated
chemical shifts of C5 and C8 in Ia are δC 112.75 and
113.22 ppm, respectively; these values are consider-
ably lower than the next following calculated chemical
shift of C7 (δC 121.08 ppm). The theoretical predictions
are completely confirmed by the experimental data not
only for compounds I and IV but also for other
triazolobenzimidazoles reported previously [12, 14]. In
the molecule of triazolobenzimidazole Ia, the most
shielded carbon nuclei are C8 (δC 110.11 ppm), C5
(112.75), and C7 (121.08), and the carbon chemical
shifts in known 2-methylaminotriazolobenzimidazole
[12] increase in the series (δC, ppm): C8 (108.28) <
C5 (111.95) < C6 (120.56) < C7 (121.23) < C8a (124.52) <
C4a (132.49) < C3a (152.87) < C2 (168.32), which
almost coincides with that observed for compounds I
and IV. No increased shielding of carbon nuclei was
noted for the compounds described in [1]. The two
most upfield carbon signals from the heteroaromatic
system, which were not assigned in [1], were located at
about δC 128 ppm, closely to signals from other carbon
nuclei (δC ~129 ppm).
of the triazolobenzimidazole structure to the products
obtained by oxidation of 2-amino-1-arylmethylidene-
aminobenzimidazoles with (diacetoxy-λ3-iodanyl)ben-
zene [1]. Therefore, further study on the structure of
these compounds seems to be intriguing.
EXPERIMENTAL
The IR spectra were recorded on a Varian Excalibur
3100 FT-IR spectrometer from solid samples. The
1H NMR spectra of Ie and IVf were obtained on
a Varian Unity-300 spectrometer (300 MHz), and the
1H, 13C (with decoupling from protons), and 15N NMR
spectra of the other compounds were measured on
a Bruker Avance 600 instrument; DMSO-d6 was used
1
as solvent and reference (for H and 13C). The 15N
chemical shifts are given relative to ammonia. Signals
in the NMR spectra were assigned using 1H–1H COSY
1
[16, 17], H–13C HSQC (hsqcetgp) [18], and HMBC
1
(1H–13C and H–15N; hmbcgpndqf) techniques [19,
20]; sample concentration 0.1 M, operating frequencies
600 (1H), 150 (13C), and 60 MHz (15N); PABBO
Z-gradient probe; temperature 303 K; the data were
acquired using standard multipulse sequences. The
mass spectrum of Ia (electron impact, 70 eV) was re-
corded on a Finnigan MAT INCOS 50 mass spectrom-
eter with direct sample admission into the ion source.
The progress of reactions was monitored, and the
purity of the products was checked, by TLC on
aluminum oxide plates (activity grade III) using
chloroform as eluent; spots were visualized by treat-
ment with iodine vapor.
The geometric parameters of molecules III, V, and
VI were optimized using Firefly 7.1G program [21]
partly based on the Gamess code [22]. The energy
minima were localized by calculating force constant
matrices. The chemical shifts were calculated using
DeMon 2K 1.0.4 and DeMonMAG [23] with the
PW91PW91 functional and IGLO-II basis set.
The structure of compounds I as 2-substituted
triazolobenzimidazoles is also convincingly confirmed
by the mass spectrum of Ia. The spectrum contains
a strong molecular ion peak with m/z 248 (100%) and
fragment ion peaks corresponding to protonated and
nonprotonated nitrile species which are typical of
nitrogen-containing heterocycles with an endocyclic
N–N bond [15].
1H-Benzimidazole-1,2-diamine (II) was synthe-
sized according to the procedure described in [4];
carboxylic acid chlorides were commercial products
(Aldrich).
(4-Methylphenyl)[2-(4-methylphenyl)-4H-[1,2,4]-
triazolo[1,5-a]benzimidazol-4-yl]methanone (III).
A mixture of 0.75 g (5 mmol) of compound II and
2.7 ml (20 mmol) of p-toluoyl chloride was heated for
2 h at 160°C. The mixture was cooled, treated with
25 ml of water, and left to stand for 4–5 h. The precip-
itate was filtered off and washed on a filter with water,
Thus, analysis of published data on [1,2,4]triazolo-
[1,5-a]benzimidazoles and the results of our present
study convincingly demonstrate erroneous assignment
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

2-ARYL(HETARYL)-4H-[1,2,4]TRIAZOLO[1,5-a]BENZIMIDAZOLES
901
a small amount of alcohol, and diethyl ether (to re-
move excess p-toluic acid). Yield 1.60 g (87%), color-
less crystals, mp 234–235°C (from toluene). IR spec-
trum, ν, cm–1: 1696 s (C=O), 1554 m, 1425 s, 1309 v.s,
7.7 Hz), 7.32 t (1H, 6-H, J = 7.7 Hz), 7.51 d (1H, 5-H,
J = 8.1 Hz), 7.77 d (1H, 8-H, J = 8.1 Hz), 7.99 d (2H,
2′-H, 6′-H, J = 8.0 Hz), 12.05 br.s (1H, NH). Two-
dimensional HMBC spectra, δ, ppm (intensity, cross-
peak), 13C–1H: 20.62, 7.99 (1.5, 4′-CH3/2′-H); 20.90,
7.26 (85.3, 4′-CH3/3′-H); 110.33, 7.51 (6.7, C8/5-H);
110.50, 7.33 (76.6, C8/6-H); 110.65, 7.26 (15.1,
C8/7-H); 113.04, 7.27 (83.5, C5/7-H); 113.05, 7.32
(13.2, C5/6-H); 113.07, 7.78 (3.8, C5/8-H); 121.50,
7.51 (67.2, C7/5-H); 121.51, 7.32 (3.9, C7/6-H);
124.02, 7.78 (57.5, C6/8-H); 124.04, 7.32 (10.4,
C8a/6-H); 124.06, 7.51 (74.4, C6/5-H); 124.11, 7.26
(77.0, C6/7-H, C8a/7-H); 126.30, 2.32 (11.4,
C2′/4′-CH3); 126.31, 7.25 (13.2, C2′/3′-H); 129.04, 7.25
(244.4, C1′/3′-H); 129.38, 7.98 (9.8, C3′/2′-H); 129.39,
2.32 (898.4, C3′/4′-CH3); 134.12, 7.26 (7.0, C4a/7-H);
134.41, 7.33 (67.5, C4a/6-H); 134.42, 7.78 (61.2,
C4a/8-H); 138.93, 2.32 (595.8, C4′/4′-CH3); 138.95,
7.99 (117.5, C4′/2′-H); 138.98, 7.25 (1.0, C4′/3′-H); C3a
showed no cross-peaks; 164.61, 7.99 (80.9, C2/2′-H);
164.75, 2.32 (6.2, C2/4′-CH3); 164.76, 7.25 (1.6,
C2/3′-H); 15N–1H: 101.29, 7.51 (15.5, N4/5-H); 101.30,
7.32 (1.0, N4/6-H); 208.45, 7.26 (2.2, N9/7-H); 208.45,
7.77 (19.1, N9/8-H); 208.98, 7.51 (3.3, N9/5-H). Mass
spectrum, m/z (Irel, %): 248 (100) [M]+, 222 (1.7) [M –
CH≡CH]+, 208 (0.8) [M – Me–C≡CH]+, 182 (0.2) [M –
CH≡CH – MeC≡CH]+, 158 (0.8) [M – p-MeC6H4]+,
144 (1.7) [M – C6H4N2]+, 131 (8.3) [M – p-MeC6H4-
CN]+, 118 (10.0) [p-MeC6H4C≡NH]+, 116 (4.2)
[NCC6H4CH2]+, 104 (5.0) [C6H4N2]+, 102 (4.9)
[PhNC]+, 91 (4.2) [C7H7]+, 90 (4.1) [C7H6]+, 77 (3.3)
[Ph]+, 65 (1.7) [C5H5]+, 51 (1.7) [C4H3]+. Found, %:
C 72.61; H 4.73; N 22.38. C15H12N4. Calculated, %:
C 72.56; H 4.87; N 22.57.
1
1074 s, 754 v.s, 737 v.s. H NMR spectrum,*** δ,
ppm: 2.34 s (3H, 4′-CH3), 2.48 s (3H, 4″-CH3), 7.25–
7.27 m (2H, 3′-H, 5′-H), 7.39–7.43 m (2H, 3″-H,
5″-H), 7.51 t.d (1H, 7-H, J = 7.8, 1.5 Hz), 7.54 t.d (1H,
6-H, J = 7.7, 1.3 Hz), 7.80–7.82 m (2H, 2′-H, 6′-H),
7.91 d.d.d (1H, 8-H, J = 7.8, 1.6, 0.8 Hz), 7.94–7.98 m
(2H, 2″-H, 6″-H), 8.25 d.d.d (1H, 5-H, J = 7.9, 1.3,
0.7 Hz). Two-dimensional HMBC spectra, δ, ppm (in-
tensity,**** cross-peak): 13C–1H: 21.03, 7.26 (638,
4′-CH3/3′-H); 21.44, 7.41 (484, 4″-CH3/3″-H); 110.33,
7.51 (20, C8/7-H); 110.50, 7.54 (125, C8/6-H); 117.30,
7.54 (7.8, C5/7-H); 117.31, 7.51 (1.0 C5/6-H); 125.12,
7.51 (495, C7/6-H); 125.12, 8.24 (1245, C7/5-H,
C6/5-H, C8a/5-H, common peak); 125.13, 7.54 (23,
C6/7-H, C8a/7-H); 125.13, 7.92 (36, C6/8-H, C7/8-H,
C8a/8-H); 125.90, 7.80 (473, C3′/2′-H); 125.95, 7.80
(473, C8a/7-H); 128.40, 2.48 (38123, C3″/4″-CH3);
128.40, 7.26 (2920, C1′/3′-H); 129.18, 7.41 (2954,
C1″/3″-H); 129.20, 2.34 (34967, C3′/4′-CH3); 132.72,
7.52 (920, C4a/6-H, C4a/7-H); 132.82, 7.92 (95,
C4a/8-H); 139.15, 7.81 (4016, C4′/2′-H); 139.29, 2.34
(21559, C4′/4′-CH3); 143.75, 7.93 (3514, C4″/2″-H);
143.86, 2.48 (23225, C4″/4″-CH3); 164.08, 7.81 (2154,
C2/2′-H); 165.54, 7.92 (2464, C=O/2″-H); 15N–1H:
148.21, 7.51 (3.5, N4/6-H); 209.60, 7.91 (1.0, N9/8-H);
209.82, 7.55 (1.2, N9/7-H). Found, %: C 75.27; H 4.83;
N 15.45. C23H18N4O. Calculated, %: C 75.39; H 4.95;
N 15.29.
2-(4-Methylphenyl)-4H-[1,2,4]triazolo[1,5-a]-
benzimidazole (Ia). A suspension of 1.10 g (3 mmol)
of 4-acyl derivative III in 30 ml of a 10% solution of
sodium hydroxide was heated for 0.5 h under reflux
until it became homogeneous. The solution was cooled
and acidified with concentrated aqueous HCl to pH 3–
4, and the precipitate was filtered off and thoroughly
washed with water. Yield 0.68 g (92%), colorless fiber-
like crystals, mp 317–318°C (from DMF); published
data: mp 116–118°C [1], 330–331°C [2]. The product
was sparingly soluble in alcohol, chloroform, and
water. IR spectrum, ν, cm–1: 3017–2620 w (NH),
1602 s, 1468 s, 1225 m, 1107 m, 819 s, 741 v.s.
1H NMR spectrum, δ, ppm: 2.32 s (3H, Me), 7.24 d
(2H, 3′-H, 5′-H, J = 8.0 Hz), 7.26 t (1H, 7-H, J =
2-(2-Furyl)-4H-[1,2,4]triazolo[1,5-a]benzimid-
azole (Ie). A mixture of 0.75 g of diamine II and 2 ml
(20 mmol) of 2-furoyl chloride was fused for 2 h at
150–160°C. The melt was cooled and treated with
25 ml of 10% aqueous sodium hydroxide, the mixture
was heated for 15–20 min under reflux until it became
homogeneous, 0.1 g of activated charcoal was added,
and the mixture was heated for 5–7 min under reflux
and filtered while hot. The filtrate was cooled and
acidified with concentrated aqueous HCl to pH 3–4,
and the precipitate (a mixture of compound Ie and
2-furoic acid) was thoroughly washed on a filter with
water, 3–5 ml of cold alcohol, and diethyl ether. Yield
0.95 g (85%), mp 295–296°C (from EtOH). IR spec-
trum, ν, cm–1: 3140–2530 br (NH), 1602 w, 1585 s,
**** Hereinafter, primed locants refer to the substituent on C2,
and double-primed, to the substituent on N4.
1
1513 m, 1310 s, 1223 s, 1170 s, 738 v.s. H NMR
**** Given are intensities relative to the weakest cross-peak.
spectrum, δ, ppm: 6.55 d.d (1H, 4′-H, J = 3.3, 1.8 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

MORKOVNIK et al.
902
6.93 d.d (1H, 3′-H, J = 3.3, 0.9 Hz), 7.22–7.32 m (2H,
6-H, 7-H), 7.47 d (1H, 5-H, J = 7.5 Hz), 7.65 d.d
(1H, 5′-H, J = 1.8, 0.9 Hz), 7.74 d (1H, 8-H, J =
7.8 Hz), 12.25 s (1H, NH). Found, %: C 64.35; H 3.72;
N 24.78. C12H8N4O. Calculated, %: C 64.28; H 3.60;
N 24.99.
acetone, and 0.25 ml (4 mmol) of methyl iodide was
added. The mixture was stirred for 2 h at 20–25°C and
evaporated, the residue was treated with 15 ml of
chloroform, and the solution was passed through a col-
umn charged with Al2O3 (10×1.5 cm) using chloro-
form as eluent. A fraction with Rf 0.7 was collected.
Yield 0.54 g (76%), colorless crystals which darkened
2-(2-Thienyl)-4H-[1,2,4]triazolo[1,5-a]benzimid-
azole (If) was synthesized as described above for Ie
from diamine II and 2-thenoyl chloride. Yield 82%,
light yellow crystals, mp 336–337°C (from DMF).
1H NMR spectrum, δ, ppm: 7.17 d.d (1H, 3′-H, J = 5.0,
3.6 Hz), 7.30 distorted d.d.d (1H, 7-H, J = 7.9 Hz),
7.36 distorted d.d.d (1H, 6-H, J = 7.7 Hz), 7.55 d (1H,
5-H, J = 8.0 Hz), 7.63 d.d (1H, 2′-H, J = 5.0, 1.2 Hz),
7.69 d.d (1H, 4′-H, J = 3.6, 1.2 Hz), 7.82 d (1H, 8-H,
J = 7.8 Hz), 12.41 br.s (1H, NH). 13C NMR spectrum,
δC, ppm: 110.34 (C8), 112.96 (C5), 121.37 (C7), 123.64
(C8a), 123.94 (C6), 126.13 (C3′), 127.28 (C5′), 127.90
(C4′), 134.08 (C4a), 134.58 (C2′), 153.74 (C3a), 160.23
(C2). Two-dimensional HMBC spectra, δ, ppm:
13C–1H: 110.31, 7.55 (18.9, C8/5-H); 110.51, 7.37
(185.4, C8/6-H); 110.69, 7.30 (51.3, C8/7-H); 112.95,
7.37 (55.4, C5/6-H); 113.01, 7.30 (204.2, C5/7-H);
113.01, 7.82 (10.1, C5/8-H); 121.34, 7.55 (149.8,
C7/5-H); 121.57, 7.37 (7.7, C7/6-H); 123.64, 7.37
(37.1, C8a/6-H); 123.72, 7.30 (150.7, C8a/7-H); 123.73,
7.55 (138.7, C8a/5-H); 123.98, 7.82 (120.1, C6/8-H);
124.16, 7.30 (11.6, C6/7-H); 124.16, 7.55 (11.8,
C6/5-H); 126.22, 7.17 (80.5, C3′/4′-H); 126.23, 7.63
(66.5, C3′/5′-H); 127.36, 7.17 (99.4, C5′/4′-H); 127.36,
7.69 (69.8, C5′/3′-H); 127.92, 7.63 (40.2, C4′/5′-H);
127.98, 7.69 (28.0, C4′/3′-H); 134.13, 7.82 (121.3,
C4a/8-H); 134.16, 7.37 (164.8, C4a/6-H); 134.21, 7.30
(7.7, C4a/7-H); 134.62, 7.17 (230.1, C2′/4′-H); 134.63,
7.63 (62.7, C2′/5′-H); 134.66, 7.69 (87.3, C2′/3′-H);
C3a showed no cross peaks; 160.27, 7.17 (1.6,
C2/4′-H); 160.28, 7.63 (1.3, C2/5′-H); 160.34, 7.69
(63.3, C2/3′-H); 15N–1H: 99.87, 7.36 (232.4, N4/6-H);
no N4/7-H peak; 99.87, 7.55 (206.7, N4/5-H); 99.90,
7.82 (1.0, N4/8-H); 192.90, 7.63 (2.9, N3/4′-H); 192.90,
7.69 (1.5, N3/2′-H); 193.60, 7.17 (62.6, N3/3′-H);
208.70, 7.30 (203.7, N9/7-H); 208.70, 7.55 (70.5,
N9/5-H); 208.70, 7.82 (345.1, N9/8-H); 253.10, 7.17
(219.5, N1/3′-H); 253.10, 7.69 (21.8, N1/2′-H). Found,
%: C 59.78; H 3.47; N 23.54; S 13.17. C12H8N4S. Cal-
culated, %: C 59.98; H 3.36; N 23.32; S 13.34.
1
on storage, mp 139–140°C (from EtOAc). H NMR
spectrum, δ, ppm: 3.83 s (3H, Me), 6.66 d.d (1H, 4′-H,
J = 3.4, 1.8 Hz), 7.04 d.d (1H, 3H, J = 3.4, 0.8 Hz),
7.34 d.d.d (1H, 7-H, J = 8.1, 7.3, 1.1 Hz), 7.43 d.d.d
(1H, 6-H, J = 8.3, 7.83, 1.2 Hz), 7.69 d.m (1H, 5-H,
J = 8.1 Hz), 7.83 d.d (1H, 5′-H, J = 1.8, 0.8 Hz),
7.83 d.d.d (1H, 8-H, J = 8.0, 1.2, 0.6 Hz). 13C NMR
spectrum, δC, ppm: 29.65 (Me), 109.77 (C3′), 110.29
(C8), 111.34 (C5), 111.73 (C4′), 121.48 (C7), 123.23
(C8a), 123.86 (C6), 135.25 (C4a), 143.93 (C5′), 146.55
(C2′), 154.17 (C3a), 157.05 (C2). Two-dimensional
HMBC spectra, δ, ppm: 13C–1H: 109.85, 6.66 (112.4,
C3′/4′-H); 110.01, 7.83 (132.9, C3′/5-H); 110.41, 7.42
(304.2, C8/6-H); 110.58, 7.33 (93.3, C8/7-H); 111.31,
7.42 (61.3, C5/6-H); 111.31, 7.83 (279.6, C5/8-H);
111.34, 7.33 (374.4, C5/7-H); 111.79, 7.03 (145.7,
C4′/3′-H); 121.67, 7.69 (264.0, C7/5-H); 121.82, 7.42
(36.1, C7/6-H); 123.00, 7.69 (382.7, C8a/5-H); 123.02,
7.42 (71.2, C8a/6-H); 123.20, 7.83 (9.9, C8a/8-H);
123.34, 7.33 (310.4, C8a/7-H); 123.76, 7.69 (8.1,
C6/5-H); 123.80, 7.83 (202.1, C6/8-H); 135.27, 3.82
(1811.5, C4a/4-CH3); 135.27, 7.42 (279.5, C4a/6-H);
135.29, 7.83 (227.3, C4a/8-H); 135.41, 7.33 (73.0,
C4a/7-H); 144.05, 6.66 (195.9, C5′/4′-H); 146.33, 7.03
(448.8, C2′/3′-H); 146.53, 6.66 (318.3, C2′/4′-H);
146.64, 7.83 (163.9, C2′/5′-H); 154.24, 3.82 (2181.9,
C3a/4-CH3); 157.06, 6.66 (1.0, C2/4-H); 157.06, 7.04
(27.5, C2/3-H); 157.13, 7.83 (11.2, C2/8-H); 15N–1H:
94.19, 3.82 (705.4, N4/4-CH3); 94.19, 7.42 (5.1,
N4/6-H); 94.19, 7.69 (49.4, N4/5-H); 94.19, 7.83 (1.0,
N4/8-H); 205.82, 7.33 (7.7, N9/7-H); 205.82, 7.68
(9.6, N9/5-H); 205.82, 7.83 (58.7, N9/8-H). Found, %:
C 65.66; H 4.37; N 23.38. C13H10N4O. Calculated, %:
C 65.54; H 4.23; N 23.52.
4-Methyl-2-(2-thienyl)-4H-[1,2,4]triazolo[1,5-a]-
benzimidazole (IVf) was synthesized as described
above for compound IVe from triazolobenzimidazole
If. Yield 72%, colorless crystals, mp 130–131°C.
1H NMR spectrum, δ, ppm: 3.88 s (3H, Me), 7.12 d.d
(1H, 4′-H, J = 6.9, 3.5 Hz), 7.28–7.41 m (4H, 3′-H,
5-H, 6-H, 7-H), 7.79 d.d (1H, 5′-H, J = 3.5, 1.3 Hz),
7.82 d (1H, 8-H, J = 8.1 Hz). Found, %: C 61.54;
H 4.07; N 22.17; S 12.50. C13H10N4S. Calculated, %:
C 61.40; H 3.96; N 22.03; S 12.61.
2-(2-Furyl)-4-methyl-4H-[1,2,4]triazolo[1,5-a]-
benzimidazole (IVe). A solution of 0.67 g (3 mmol) of
triazolobenzimidazole Ie and 0.22 g (4 mmol) of
potassium hydroxide in 1.5 ml of water was evaporat-
ed to dryness, the residue was dispersed in 10 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

2-ARYL(HETARYL)-4H-[1,2,4]TRIAZOLO[1,5-a]BENZIMIDAZOLES
903
11. Claramunt, R.M., Alkorta, I., Lopez, C., Elguero, J.,
Garcıa, M.A., and Denisov, G.S., New J. Chem., 2003,
vol. 27, p. 734; Witanowski, M., Stefaniak, L., and
Webb, G.A., Annu. Rep. NMR Spectrosc., 1993, p. 41.
This study was performed using the facilities of
“Molecular Spectroscopy” shared research center of
the Southern Federal University.
12. Molina, P., Aller, E., and Lorenzo, A., Heterocycles,
REFERENCES
1994, vol. 37, p. 997.
1. Kumar, A., Parshad, M., Gupta, R.K., and Kumar, D.,
Synthesis, 2009, p. 1663.
2. Rao, J.P. and Reddy, K.K., Synth. Commun., 1988,
13. Mohamed, B.G., Hussein, M.A., Abdel-Alim, A.-A.M.,
and Hashem, M., Arch. Pharm. Res., 2006, vol. 29,
p. 26.
vol. 18, p. 1995.
3. Ho, R.I.-F. and Day, A.R., J. Org. Chem., 1973, vol. 38,
14. Kuz’menko, T.A., Kuz’menko, V.V., Divaeva, L.N.,
Morkovnik, A.S., and Borodkin, G.S., Izv. Akad. Nauk,
Ser. Khim., 2012, p. 1150.
p. 3084.
4. Kuz’menko, V.V., Kuz’menko, T.A., Pozharskii, A.F.,
Doron’kin, V.N., Chikina, N.L., and Pozharskaya, S.S.,
Khim. Geterotsikl. Soedin., 1989, p. 209.
5. Badr, M.Z.A., Mahmoud, A.M., Mahgoub, S.A., and
Hozien, Z.A., Bull. Chem. Soc. Jpn., 1988, vol. 61,
p. 1339.
6. Wilde, H., Hauptmann, S., Ostermann, G., and
Mann, G., J. Prakt. Chem., 1984, vol. 326, p. 829.
7. Kuz’menko, T.A., Divaeva, L.N., and Morkovnik, A.S.,
15. Erra-Balsells, R., Org. Mass Spectrom., 1991, p. 293;
Cotte, J.L., Org. Mass Spectrom., 1972, p. 1071.
16. Nagayama, K., Kumar, A., Wuthrich, K., and
Ernst, R.R., J. Magn. Reson., 1980, vol. 40, p. 321.
17. Aue, W.P., Bartholdi, E., and Ernst, R.R., J. Chem.
Phys., 1976, vol. 64, p. 2229.
18. Davis, A.L., Keeler, J., Laue, E.D., and Moskau, D.,
J. Magn. Reson., 1992, vol. 98, p. 207.
19. Hurd, R.E. and John, B.K., J. Magn. Reson., 1991,
Izv. Akad. Nauk, Ser. Khim., 2011, p. 535.
vol. 91, p. 648.
8. Ogura, H., Takayanagi, H., Yamazaki, Y., Yonezawa, S.,
Takagi, H., Kobayashi, S., Kamioka, T., and Kamo-
shita, K., J. Med. Chem., 1972, vol. 15, p. 923; Anisi-
mova, V.A., Simonov, A.M., and Borisova, T.A., Khim.
Geterotsikl. Soedin., 1973, p. 791; Kuz’menko, T.A.,
Kuz’menko, V.V., Pozharskii, A.F., and Anisimo-
va, V.A., Khim. Geterotsikl. Soedin., 1990, p. 1517.
9. Mas, Th., Claramunt, R.M., Santa María, M.D.,
Sanz, D., Alarcón, S.H., Pérez-Torralba, M., and El-
guero, J., Arkivoc, 2002, part (v), p. 48; Catalan, J.,
de Paz, J.L.G., del Valle, J.C., Claramunt, R.M., and
Mas, Th., Chem. Phys., 2004, vol. 305, p. 175.
20. Willker, W., Leibfritz, D., Kerssebaum, R., and
Bermel, W., Magn. Reson. Chem., 1993, vol. 31, p. 287.
21. Granovsky, A.A., www.classic.chem.msu.su/gran/firefly/
index.htm
22. Schmidt, M.W., Baldridge, K.K., Boatz, J.A., El-
bert, S.T., Gordon, M.S., Jensen, J.H., Koseki, Sh.,
Matsunaga, N., Nguyen, K.A., Su, Sh., Windus, Th.L.,
Dupuis, M., and Montgomery, J.A., Jr., J. Comput.
Chem., 1993, vol. 14, p. 1347.
23. Koester, A.M., Flores-Moreno, R., Geudtner, G.,
Goursot, A., Heine, Th., Reveles, J.U., Patchkovskii, S.,
Vela, A., and Salahub, D.R., DeMon Developers,
DeMon2K 1.0.4, NRC, Canada, 2004.
10. Malkin, V.G., Malkina, O.L., Casida, M.E., and Sala-
hub, D.S., J. Am. Chem. Soc., 1994, vol. 116, p. 5898.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013