Synthesis and some transformations of trans-1-methyl-2-[β-(2′- thienyl)vinylene]-1H-benzimidazole

Article abstract of DOI:10.1134/S1070363213010155

The condensation of 1,2-dimethylbenzimidazole with thiophene-2-aldehyde in the presence of fused zinc chloride results in 1-methyl-2-[β-(2-thienyl) vinylene]-1H-benzimidazole. Its electrophilic substitution reactions (nitration, bromination, sulfonation,

Full text of DOI:10.1134/S1070363213010155

ISSN 1070-3632, Russian Journal of General Chemistry, 2013, Vol. 83, No. 1, pp. 91–94. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © E.V. Illenzeer, M.M. El’chaninov, A.A. Alexandrov, 2013, published in Zhurnal Obshchei Khimii, 2013, Vol. 83, No. 1, pp. 99–102.
Synthesis and Some Transformations
of trans-1-Methyl-2-[β-(2'-thienyl)vinylene]-1H-benzimidazole
E. V. Illenzeer, M. M. El’chaninov, and A. A. Alexandrov
South-Russian State Technical University, ul. Prosveshcheniya 132, Novocherkassk, 346428 Russia
e-mail: aaanet1@yandex.ru
Received December 12, 2011
Abstract—The condensation of 1,2-dimethylbenzimidazole with thiophene-2-aldehyde in the presence of
fused zinc chloride results in 1-methyl-2-[β-(2-thienyl)vinylene]-1H-benzimidazole. Its electrophilic
substitution reactions (nitration, bromination, sulfonation, formylation, acylation) were studied. All the reac-
tions occur in the 5-position of the thiophene ring. Only in the case of bromination in dichloroethane 5',5(6)-
dibromo-derivative was obtained. Data of the quantum-chemical calculations of the total positive charge on the
carbon atoms of the protonated molecules of thienylbenzimidazoles including the vinylene group and without it
are reported.
DOI: 10.1134/S1070363213010155
The mutual influence of heterocyclic rings in
bihetaryls is an interesting and as yet poorly studied
problem. The scarcest data are on the reactivity of
compounds in which benzothiazole and π-excessive
thiophene rings are linked to each other. Previously the
reactivity of furylvinylbenzimidazole was studied [1].
Introducing the substituents containing a π-system into
the benzimidazole molecule increases the fluorescence
quantum yield. To this type belong, for example,
benzimidazolylstilbenes containing benzene and pyri-
dine rings used as the optical bleaching agents [2, 3].
enetetramine and carboxylic acids in polyphosphoric
acid (PPA) (Table 1).
A comparison of the chemical shifts of the Н3'
protons (7.22 and 7.51 ppm) of the 2-thienyl group in
the 1H NMR spectra of compounds I and II shows that
in these compounds the proton of I is the most strongly
shielded. This is primarily due to the inductive effect
and the deshielding (electron-acceptor) effect of the
benzimidazole substituents, which is less in the first
case. Therefore, we can expect a high reactivity of the
thiophene ring in compound I.
The goal of our study was to develop or to choose a
convenient synthesis method and to examine the
relative reactivity of 1-methyl-2-[β-(2-thienyl)vinyl-
ene]benzimidazole I and to compare it with that of the benz-
imidazole analog II lacking the vinylene group [4].
Our studies confirm this assumption. Thus, the
nitration of 1-methyl-2-[β-(2-thienyl)vinylene]-1H-
benz-imidazole I proceeds under mild conditions by
the action of Cu(NO3)2 and acetic anhydride at 10°C
(yield of 5-nitro-derivative III was 75%), while
compound II is nitrated with a mixture of fuming nitric
acid (d 1.51 g cm–3) and acetic anhydride at 0°C [4].
We failed in similar to carry out the selective nitration
of compound I. Unlike benzimidazole II, the bro-
mination of I with bromine in acetic acid at 20°C
results also in the 5-substitution of the thiophene ring.
The bromination of compound I in refluxing di-
chloroethane proceeds interestingly: not only
thiophene ring, but also benzene moiety undergoes an
electrophilic attack. This is apparently explained by the
electron-donor effect of vinylene group in the neutral
molecule of compound I. In contrast, in an acid
N
S
N
S
N
N
Me
II
Me
I
Compound I we synthesized in ~75% yield by
heating of a mixture of 1,2-dimethylbenzimidazole
with thiophene-2-aldehyde at 160°C in the presence of
fused zinc chloride. Further compound I was brought
into reactions with the electrophilic reagents: acetyl
nitrate, bromine in dichloroethane, a mixture of
sulfuric acid and polyphosphoric acids, hexamethyl-
91

92
ILLENZEER et al.
Table 1. Yields, melting points, and elemental analysis data for compounds I, IIIa–IIIg
Found, %
Calculated, %
Comp.
no.
Yield,
%
mp, °С
Formula
С
Н
N
С
Н
N
75
76
66
57
63
89
79
83
86–87
70.29
59.33
52.97
41.89
52.76
66.79
67.73
73.49
4.88
4.11
3.59
2.76
3.93
4.33
4.93
4.87
11.72
15.04
С14H12N2S
С14H11N3O2S
69.97
58.93
52.68
42.24
52.48
67.14
68.06
73.23
5.03
3.89
3.47
2.53
3.78
4.51
5.00
4.68
11.66
14.72
25.03Br
40.14Br
8.74
10.4
9.92
8.13
I
215–216
123–124
144–145
295–296
176–177
220–221
174–175
IIIа
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
25.40 Br С14H11BrN2S
40.51 Br С14H10Br2N2S
9.03
10.79
10.22
7.73
С14H12N2O3S2
С15H12N2OS
С16H14N2OS
С21H16N2OS
medium (AcOH) the transformation of the substrate
into the cationic form is passivated by the benz-
imidazole fragment. As a result, the reaction involves
exclusively the thiophene moiety.
R
C(O)R'
S
N
S
Cu(NO3)2/Ac2O
Br2/AcOH
R'COOH/(CH2)6N4
S
PPA
N
IIIа, IIIb
IIIe−IIIg
Me
H2SO4
I
Br2
C2H4Cl2
PPA
H
N
N
N+
Br
SO3−
S
S
Br
N
Me
Me
IIIc
IIId
R = NO2 (a), Br (b), R' = H (e), Me (f), Ph (g).
Previously, the sulfonation of 1-methyl-2-(2'-
thienyl)benzimidazole II was performed by the action
of concentrated sulfuric acid and polyphosphoric acid
at 120°C [4]. In these conditions a strong tarring was
observed. Therefore the synthesis of sulfonic acid IIId
(in 63% yield) was performed at 60°C. Similar to
sulfonic acid of compound II, the acid IIId also exists
in the betaine form. In the lН NMR spectrum the signal
of the sulfo group proton was observed at 12.32 ppm
only in trifluoroacetic acid solution (Table 2).
acid also occurs under mild conditions (50–60°С, 1–2 h)
to afford the 5'-acyl derivatives IIIf and IIIg, whereas
in the case of compound II the acyl derivatives were
obtained at 110–150°С within 20 h in 22–51% yields.
The comparison of the behavior of thienyl-
benzimidazole II and thienylvinylenebenzimidazole I
in the electrophilic substitution reactions shows that
they form a 5'-substituted thiophene derivatives.
However, the reactions of compound I occur much
faster and under milder conditions than those of II.
The presence of the vinylene group between the rings
weakens the deshielding effect of the benzimidazole
substituent on the thiophene ring. The quantum-
chemical calculations by the B3LYP/6-31G(d, p)
method confirm this assumption. Thus, a net positive
charge on the carbon atoms of the thiophene ring in the
protonated molecules of compounds I and II (since the
reactions proceed in the acidic medium) equals
(+0.065) and (+0.113), respectively. In addition, unlike
Since the formylation of compound II with the
Vilsmeier reagent was unsuccessful, in this work for
the formylation of III we used hexamethylene-
tetramine in polyphosphoric acid at 60°C. The reaction
occurs in 0.5 h to give aldehyde IIIe in 89% yield. For
comparison, the formylation of compound II
proceeded over 10 h [5].
The acylation of compound I by the action of
carboxylic acids in the presence of polyphosphoric
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 83 No. 1 2013

SYNTHESIS AND SOME TRANSFORMATIONS
Table 2. Spectral parameters of compounds I, IIIa–IIIg
93
Comp.
no.
IR spectrum, ν, cm–1
1Н NMR spectrum, δ, ppm (J, Hz, СDCl3)
–
3.87 s (3H, NCH3), 6.89 d (1H, Hvinyl, J 15.8), 7.05 t (1H, H4', J 5.0), 7.12 d (1H, H3', J 3.9), 7.25–7.29
I
m (3H, 5,6,7-HAr), 7.37 d (1Н, Н5', J 5.5), 7.70–7.73 m (1H, 4-HAr), 8.03 d (1H, Hvinyl, J 15.8)
1370 s (NO2)
3.88 s (3H, NCH3), 7.09 d (1H, Hvinyl, J 15.5), 7.13 d (1H, H3', J 4.3), 7.29–7.36 m (3H, 5,6,7-HAr),
IIIа
IIIb
IIIc
IIIdа
IIIe
IIIf
IIIg
1530, 1550 as (NO2) 7.73–7.76 m (1H, 4-HAr), 7.85 d (1H, H4', J 4.3), 7.99 d (1H, Hvinyl, J 15.5)
–
3.88 s (3H, NCH3), 7.07 d (1H, H4', J 3.7), 7.15 d (1H, Hvinyl, J 15.8), 7.17 d (1H, H3', J 3.7), 7.27–
7.31 m (3H, 5,6,7-HAr), 7.69–7.72 m (1H, 4-HAr), 8.02 d (1H, Hvinyl, J 15.8)
3.89 s (3H, NCH3), 7.08 d (1H, H4', J 3.8), 7.17 d (1H, Hvinyl, J 15.9), 7.17 d (1H, H3', J 3.8), 7.31 d
(2H, 6,7-HAr, J 7.9), 7.75 s (1H, 4-HAr), 8.00 d (1H, Hvinyl, J 15.9)
–
1260 (SO2)
1680 (C=O)
1650 (C=O)
1670 (C=O)
3.80 s (3H, NCH3), 6.85 d (1H, Hvinyl, J 16.0), 7.10 d (1H, H3', J 4.0), 7.28 s (4H, 4,5,6,7-НАr), 7.52 d
(1H, H4', J 4.0), 7.68 d (1H, Hvinyl, J 16.0), 11.95 s (1H, SO2OH)
3.87 s (3H, NCH3), 7.09 d (1H, Hvinyl, J 15.5), 7.30 d (1H, H3', J 3.9), 7.29–7.34 m (3H, 5,6,7-HAr),
7.69 d (1H, H4', J 3.9), 7.73–7.76 m (1H, 4-HAr), 8.07 d (1H, Hvinyl, J 15.5), 9.89 s (1H, CHO)
2.55 s (3H, CH3), 3.88 s (3H, NCH3), 7.09 d (1H, Hvinyl, J 15.8), 7.28 d (1H, H3', J 4.0), 7.30–7.34 m
(3H, 5,6,7-HAr), 7.67 d (1H, H4', J 4.0), 7.73–7.77 m (1H, 4-HAr), 8.05 d (1H, Hvinyl, J 15.8)
3.88 s (3H, NCH3), 7.10 d (1H, Hvinyl, J 16.0), 7.28 d (1H, H3', J 4.1), 7.30–7.34 m (3H, 5,6,7-HAr),
7.53 t (3H, 3,4,5-HAr, J 7.5), 7.69 d (1H, H4', J 4.1), 7.73–7.77 m (1H, 4-HAr), 7.91 d (2H, 2,6-HAr, J
7.2), 8.03 d (1H, Hvinyl, J 16.0)
a 1H NMR spectrum is removed in trifluoroacetic acid.
the previously studied furan analogs [1], compounds
IIIe–IIIg were found to undergo no changes in the
trans-orientation of the substituents at the double bond.
The toluene and acetonitrile solutions of compounds
IIIe–IIIg fluoresce strongly when irradiated with UV
light, which suggests their photoluminescent properties.
water. The precipitate was separated and crystallized
from heptane. The yield, melting point, and elemental
analysis data of I are given in Table 1.
1-Methyl-2-[β-(5-nitrothien-2-yl)vinylene]-1H-
benzimidazole (IIIa). Preparation of the nitrating
mixture: to 16.9 g (70 mmol) of Cu(NO3)2·3H2O was
added in small portions 40 ml of acetic anhydride with
cooling, making sure that the temperature of the
reaction mixture does not rise above 30–40°С. When
the exothermic reaction completed, the mixture was
kept at room temperature for 24 h. After the precipitate
of copper(II) acetate was filtered off, the resulting
mixture was stored no more than 10 days at 5–10°С.
EXPERIMENTAL
The IR spectra were recorded on a Specord 75 IR
1
spectrometer for the samples in chloroform. The H
NMR spectra were taken on a Varian Unity 300
instrument (300 MHz) in the pulsed Fourier mode
relative to the residual proton signals of CDCl3 and
DMSO-d6 (δ 7.26 and 2.50 ppm, respectively). The
elemental analysis was carried out on a Perkin-Elmer
2400 instrument. The melting points were determined
by the capillary method. The reaction progress and
individuality of the synthesized compounds were
monitored by TLC using the plates coated with Al2O3
of II degree of the Brockman activity (detecting with
iodine vapor) or Silufol UV-254 plates.
To a solution of 1.20 g (5 mmol) of compound I in
5 ml of acetic anhydride was added dropwise 1.4 ml of
the nitrating mixture under vigorous stirring at room
temperature over 330–40 min. The mixture was diluted
with 25 ml of cold water and neutralized with 25%
solution of ammonia. The precipitate was separated,
washed thoroughly with water, and crystallized from a
benzene–heptane mixture (1:1).
1-Methyl-2-[β-(thien-2-yl)vinylene]-1H-benzimi-
dazole (I). A mixture of 4.48 g (40 mmol) of
thiophene-2-aldehyde, 5.84 g (40 mmol) of 1,2-di-
methylbenzimidazole and 0.9 g (0.07 mol) of fused
zinc chloride was heated for 3 h at 160°C. The reaction
mixture was cooled and triturated with acetone and
1-Methyl-2-[β-(5-bromothien-2-yl)vinylene]-1H-
benzimidazole (IIIb). To a solution of 1.20 g
(5 mmol) of compound I in 20 ml of acetic acid was
slowly added 1.6 g (10 mmol) of bromine in 10 ml of
acetic acid under vigorous stirring at 50°C. The
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94
ILLENZEER et al.
reaction mixture was kept at this temperature for 1 h.
The precipitated hydrobromide IIIb was separated.
The free base was obtained by the action of 50 ml of
10% aqueous ammonia solution followed by re-
crystallization from heptane.
The reaction product was extracted with 50 ml of chloro-
form and chromatographed on a column (h 20 cm, d
2.5 cm) filled with alumina, eluting with chloroform.
The target compound was recrystallized from aqueous
alcohol.
1-Methyl-5(6)-bromo-2-[β-(5-bromothien-2-yl)-
vinylene]-1H-benzimidazole (IIIc). To a solution of
1.20 g (5 mmol) of compound I in 10 ml of dichloro-
ethane at 80°C was gradually added a solution of 2.4 g
(15 mmol) of bromine in 10 ml of dichloroethane.
After heating at the same temperature for 2 h the re-
action mixture was cooled and concentrated. The
residue was neutralized with aqueous ammonia and
extracted with 2×25 ml of chloroform. The extract was
dried, concentrated, and chromatographed on a column
(h 20 cm, d 2.5 cm) filled with alumina eluting with
chloroform. After chloroform removal, the residue was
recrystallized from n-octane.
1-Methyl-2-[β-(5-acetylthien-2-yl)vinylene]-1H-
benzimidazole (IIIf). A mixture of 1.20 g (5 mmol) of
compound I and 0.6 g (10 mmol) of glacial acetic acid
in 20 g of polyphosphoric acid was stirred at 50°C for
1 h. Then the reaction mixture was diluted with 75 ml
of water and neutralized with ammonia. Further
isolation of the reaction product was carried out
similarly to compound IIIe.
1-Methyl-2-[β-(5-benzoylthien-2-yl)vinylene]-
1H-benzimidazole (IIIg). A mixture of 1.20 g (5 mmol)
of compound I and 1.22 g (10 mmol) of benzoic acid
in 20 g of polyphosphoric acid was stirred at 60°C for
2 h. Then the benzoylation product was isolated and
purified similarly to compounds IIIe, IIIf.
1-Methyl-2-[β-(5-sulfothien-2-yl)vinylene]-1H-
benzimidazole (IIId). A mixture of 1.20 g (5 mmol)
of compound I, 0.59 g (6 mmol) of sulfuric acid (d
1.84 g cm–3), and 15 g of polyphosphoric acid was
heated at 60°C for 1 h. Then the reaction mixture was
cooled and diluted with 50 ml of water. The precipitate
was separated and recrystallized from water.
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1. El’chaninov, M.M., Stoyanov, V.V., Simonov, A.M.,
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1-Methyl-2-[β-(5-formylthien-2-yl)vinylene]-1H-
benzimidazole (IIIe). A mixture of 1.20 g (5 mmol) of
compound I and 1.40 g (10 mmol) of hexamethyl-
enetetramine in 15 g of polyphosphoric acid was
stirred at 60°C for 0.5 h. Then the reaction mixture
was diluted with 50 ml of water and carefully neu-
tralized with concentrated ammonia solution to pH 7–8.
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