New fluorogenic chemosensors derived from benzimidazole

Article abstract of DOI:10.1007/s10593-017-2037-5

[Figure not available: see fulltext.] We report the synthesis of new 1-substituted N-(anthracen-9-ylmethyl)-1H-benzimidazol-2-amines and 1,2,3-trisubstituted 1H-benzimidazolium chlorides containing anthracene fluorophores. Benzimidazol-2-amine derivatives

Full text of DOI:10.1007/s10593-017-2037-5

DOI 10.1007/s10593-017-2037-5
Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
New fluorogenic chemosensors derived from benzimidazole
Karina S. Tikhomirova1*, Ivan E. Tolpygin1, Andrey G. Starikov2, Maria A. Kaz'mina1
1
Institute of Physical and Organic Chemistry,
Southern Federal University,
194/2 Stachki Ave., Rostov-on-Don 344090, Russia; e-mail: tikhomirova_ks@mail.ru
Southern Scientific Center, Russian Academy of Sciences,
41 Chekhova Ave., Rostov-on-Don 344006, Russia; e-mail: aled@ipoc.sfedu.ru
2
Submitted November 23, 2016
Accepted December 22, 2016
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2017, 53(2), 179–185
We report the synthesis of new 1-substituted N-(anthracen-9-ylmethyl)-1H-benzimidazol-2-amines and 1,2,3-trisubstituted 1H-benz-
imidazolium chlorides containing anthracene fluorophores. Benzimidazol-2-amine derivatives exhibited high chemosensing activity
toward Н+ cations, but in neutral media – toward Zn2+ and Cd2+ cations. The quinoline-containing benzimidazolium chloride showed
fluorogenic sensor properties toward F− and CN− anions.
Keywords: amides, anthracene, benzimidazole, anions, cations, chemosensors, fluorescence, quaternary salts.
Organic chemosensors represent molecular or supra-
molecular systems that can be used for collecting
information about the qualitative and quantitative content
of specific ions or molecules in studied samples.1 Chemo-
sensors are commonly used in biology, medical diagnos-
tics, and for environmental monitoring applications.2
Fluorescent ionochromic compounds are superior to
different types of chemosensors (colorimetric, potentio-
metric, and others) due to their high sensitivity, universal
applicability, convenience of analytical procedures, suitabi-
lity for simultaneous determination of a set of spectral
parameters for the analytes in question (intensity, batho-
and hypsochromic shifts of spectral bands, quantum yield
and half-life of fluorescence).
One of the most commonly used building blocks for the
construction of biologically active molecules and drugs is
the benzimidazole system,3 which is also a structural
feature present in various ligand systems, fluorogenic and
chromogenic chemosensors,4 materials for OLED devices,5
and palladium-containing catalysts of cross-coupling
reactions.6 The presence of electron-donating pyridine
nitrogen atom with the ability to form complexes, and the
possibility of structural modifications involving several
active centers offer a range of possibilities for using
benzimidazole ring systems as a basis for the design of
effective chemosensor systems.7 Previously we have
demonstrated the possibilities for using derivatives of
benzimidazol-2-amine and its hydrogenated analog as
effective receptors for H+ and Zn2+ cations, F− anions, while
employing anthracene system in the role of a fluorophore.8
The goal of this work was to synthesize and study a
new series of chemosensors containing receptor moieties
based on the highly basic 1-alkyl- and 1-(dialkylamino)-
alkyl-1H-benzimidazol-2-amines, as well as the respective
quaternary salts. Condensation of benz-imidazoles 1а–е
with anthracene-9-carbaldehyde and reduction of the
formed imines with NaBH4 in EtOH allowed to obtain the
amines 2a–е (Scheme 1). The formation of amines 2a–е
was accompanied by the appearance of a signal in 1H NMR
spectra due to the CH2 group protons (a doublet in the
region of 5.51–5.68 ppm) and also the anthracene system
protons. Compound 2c was modified by the introduction of
an additional chelating group derived from 8-amino-
quinoline, resulting in salt 4, which contained several
0009-3122/17/53(02)-0179©2017 Springer Science+Business Media New York
179

Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
Scheme 1
potential coordination sites: a charged aminobenzimidazole
system, a quinoline moiety, as well as the 2-diethylamino-
ethyl and amide groups. The anthracene fluorophore was also
introduced into the molecular structure by combining the
starting benzimidazole amines 1c,е with N-(anthracen-
The presence of dialkylaminoalkyl substituent in benz-
imidazole ring of compounds 2c–e is expected to increase
the quenching of initial fluorescence due to the electron
density transfer from the nitrogen atom of dialkylamino
group to the anthracene system (synergistic PET effect,
Fig. 2).1e,g
9-ylmethyl)-2-chloro-N-(2-chlorophenyl)acetamide
(5).
The anthryl fluorophore and receptor in the obtained
products (salts 6c,e) were linked by an acetamide bridge.
Quaternization of the amines 1c,e and 2c was accompanied
Such compounds, as a rule, show increased sensitivity to
the рН value of the solution. The addition of trifluoroacetic
acid to acetonitrile solutions of amines 2c–e led to a sharp
increase of fluorescence intensity of such solutions by 960,
1090, and 14008e times, respectively (Fig. 1). The increase
of sensitivity to the pH value of solution when switching
from the diethylamine derivative 2c to the piperidine
derivative 2d was symbatic with the basicity values of the
respective dialkylamines (diethylamine рKа 10.98, piperi-
dine рKа 11.22).9
In order to study the influence of dialkylaminoalkyl
substituents on the chemosensor properties of compounds
2c–e, we performed a quantum-chemical study of the
structure and stability of compound 2d and its conjugated
acids. In contrast to the amines 2a,b containing methyl and
allyl groups, the molecule of 2-piperidinoethyl derivative
2d contains two competing highly basic sites that can be
protonated – the nitrogen atoms of benzimidazole and
piperidine rings. The anthryl (signal) and heterocyclic
(receptor of analytes) moieties of the molecule 2d, which
1
by the appearance of characteristic additional H NMR
signals due to the protons belonging to the aromatic rings
and CH2CO groups.
The investigation of compounds 2a,b as potential
chemosensors demonstrated their high sensitivity toward
hydrogen ions. Amines 2a,b upon excitation with light at
λexc 350 nm in acetonitrile solution exhibited anthracene
type fluorescence (three separate peaks in the region of 390–
440 nm and a shoulder at 460–470 nm), the intensity of
which was substantially diminished as a consequence of the
photoinduced electron transfer (PET) effect.1e,g The
addition of trifluoroacetic acid to acetonitrile solutions of
these compounds prevented the aforementioned effect and
led to 45-fold and 75-fold increase of the relative intensity
of fluorescence, respectively (Fig. 1).
e–
e–
Figure 1. Changes in the relative intensity of fluorescence for
compounds 2a–e (с 5 × 10−6 M) in acetonitrile upon the addition
of various cations (с 2.5 × 10−5 M), λexc 350 nm, λobs 415 nm.
Figure 2. Scheme of the possible РЕТ effect for a molecule of
amine 2d.
180

Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
were linked by a methylene bridge, were located in
mutually perpendicular planes (Fig. 3). The nitrogen atom
of NH group had a pyramidal configuration and existed in
an sp3-hybridized state.
According to energy calculations, the most favored was
protonation at the pyridine nitrogen atom of imidazole ring
with the formation of conjugated acid 2dA (Fig. 3, Table 1).
This process led to significant equalization of N–C bond
lengths in the guanidine moiety, but did not affect the
arrangement of signal and receptor moieties. The C–N
distance was reduced from 1.379 to 1.334 Å, while the
length of C=N bond increased from 1.314 to 1.355 Å,
possibly indicating a change of bond order. Besides that, a
substantial flattening was observed for the pyramidal
nitrogen atom of the amino group. Protonation at the
piperidine nitrogen atom, which led to the conjugated acid
2dB, was less favorable by 13.7 kcal/mol (Table 1). The
performed computational study confirmed that photo-
induced electron transfer from the nitrogen atom of dialkyl-
amino group to the anthracene system indeed had the
dominant effect on the desired chemosensor properties.
Accounting for solvent effects led to a noticeably
increased affinity of molecule 2d toward protons (Table 1),
which was in agreement with the previously published
data.10 The consideration of solvation effects substantially
decreased the calculated energy difference between the
conjugated acids 2dA and 2dB, practically to the level
enabling a prototropic equilibrium between these species.
Compounds 2a–e in neutral medium also exhibited a
noticeable chemosensor activity toward Zn2+ and Cd2+ cations,
in contrast to the cations of other d-block metals (Fig.1).
The benzimidazolium chlorides 4 and 6с,e, featuring salt
type structures, showed an entirely different set of chemo-
sensor properties compared to the neutral molecules 2с,e,
for which, as was shown above, a significant chelation-
enhanced fluorescence effect (CHEF effect) was caused by
the interactions with cations.1g The quaternary salt 4 was
substantially less sensitive toward hydrogen ions, while its
interactions with Cu2+ and Hg2+ cations led to a very
pronounced chelation-enhanced fluorescence quenching
effect (CHEQ effect),1g and practically completely quenched
the initial fluorescence (Table 2, Fig. 4а). The majority of
the tested anions also exhibited the CHEQ effect, but in the
case of CN− and F− anions it was accompanied by the
appearance of new, broad long-wavelength emission bands
in the region of 450 and 500 nm (Fig. 4а), which can be
used for the detection of these ions.
Figure 3. Geometric properties of structures 2d, 2dA, and 2dB,
calculated by the DFT method with B3LYP/6-31G(d,p) basis set.
Bond lengths reported in Å.
Table 1. The total energy (Еtotal), proton affinity (PA), and energy
difference between protonated forms (ΔE) in structures 2d, 2dA,
and 2dB, calculated by the DFT B3LYP/6-31G(d,p) method
without/with accounting for solvent (MeCN) effects.
Salts 6c,e were found to have even lower sensitivity
toward hydrogen ions. Metal cations also exerted only
insignificant effects on the emission intensity, while Hg2+
ions showed a noticeable CHEF effect (Table 2, Fig. 4b).
The interaction of anions with salts 6c,e in all cases led to
quenching of the initial fluorescence.
Thus, new fluorescent chemosensors on the basis of
N-(anthracen-9-ylmethyl)-1H-benzimidazol-2-amines showed
strong chemosensing performance toward Н+ cations, but in
neutral media – also toward Zn2+ and Cd2+ cations. Quinoline-
containing benzimidazolium chloride exhibited fluorogenic
chemosensor properties toward F− and CN− anions.
Structure
Etotal, au
PA, kcal/mol
ΔE, kcal/mol
−1342.236579
−1342.647946
−1342.626122
−1342.244727
−1342.705237
−1342.697629
0.0
2d
−258.1
−244.4
0.0
0.0
2dA
2dB
2d*
13.7
−289.0
−284.2
0.0
4.8
2dA*
2dB*
* Accounting for the solvent effects (MeCN).
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Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
Figure 4. Fluorescence spectra for acetonitrile solutions (с 5 × 10−6 mol/l, λexcit 350 nm) of salts 4 (a) and 6c (b) before
(graphs 1 and 1') and after the addition of H+ cations (graphs 2 and 2'), Hg2+ (graphs 3 and 3'), and CN− anion (graphs 4 and 4')
(с 2.5 × 10−5 mol/l).
Table 2. Changes in relative intensity of fluorescence (I/I0) for
(2–3 drops) was added to a solution of anthracene-9-carb-
aldehyde (2.06 g, 10 mmol) and the respective 1H-benz-
compounds 4 and 6c,e in MeCN (с 5 × 10−6 mol/l)*
imidazol-2-amine 1а–d (10 mmol) in EtOH (60–70 ml),
followed by refluxing of the mixture for 5–6 h. The
reaction mixture was further stirred and heated at 50–60°С
(in the case of precipitate formation, 5–10 ml of DMF
was added) and treated over 15–20 min with NaBH4 (1.30 g,
35 mmol). The solution was additionally stirred for another
1 h, then it was diluted with H2O (100 ml) and the excess
of NaBH4 was neutralized by the addition of 2–3% AcOH.
The mixture was cooled to 5°С and the obtained precipitate
of amine 2a–d was filtered off after 1.5–2 h, washed with
cold H2O and cold MeOH, and air-dried. The products
were purified by crystallization from suitable solvents.
N-(Anthracen-9-ylmethyl)-1-methyl-1H-benzimidazol-
2-amine (2а). Yield 2.9 g (87%), orange coarse-grained
crystalline precipitate, mp 257–258°С (PhH). IR spectrum,
ν, cm−1: 3320 (NH), 1460 (C=C), 1360 (C–N). 1H NMR spect-
rum, δ, ppm (J, Hz): 3.33 (3H, s, CH3); 4.18 (1H, t, J = 4.5,
NH); 5.68 (2H, d, J = 4.5, CH2); 7.00–7.28 (3Н, m, H Ar);
7.42–7.60 (4Н, m, H Ar); 7.64 (1Н, d, J = 7.7, H Ar); 8.06
(2Н, d, J = 8.5, H Ar); 8.37 (2Н, d, J = 8.5, H Ar); 8.51
(1H, s, H Ar). Mass spectrum, m/z (Irel, %): 337 [M]+ (21),
191 [C14H9CH2]+ (100). Found, %: C 81.80; H 5.72; N 12.48.
C23H19N3. Calculated, %: C 81.87; H 5.68; N 12.45.
Cations
Anions
Com-
pound
−
H+ Mg2+ Zn2+ Cd2+ Cu2+ Hg2+ F− H2PO4 CN− AcO−
1.67 1.33 1.22 0.89
0.18 0.24 0.36 0.39
0.04 0.06 0.06 0.06
0.03 0.05 0.05 0.08
4
0.09 0.09
1.11 1.06 1.05 0.97 0.99
6c
6e
0.54
0.61
1.09 1.05 1.09 1.00 1.00
* After the addition of cations (с 2.5 × 10−5 mol/l) and anions (с 2.5 × 10−5 mol/l),
λexcit 350 nm, λobs 415 nm.
Experimental
IR spectra were recorded on a Varian Excalibur 3100 FT-IR
instrument by the method of attenuated total reflectance
1
using a ZnSe crystal. Н NMR spectra were acquired on
Varian Unity 300 (300 MHz, compounds 2a, 3–5, 6c,e) and
Bruker Avance 600 (600 MHz, the rest of the compounds)
spectrometers. 13C NMR spectra were acqui-red on a Bruker
Avance 600 spectrometer at 150 MHz. The solvents were
CDCl3 (for compounds 2a, 3, 5) and DMSO-d6 (for the rest
of the compounds), while residual proton signals of CHCl3
and DMSO were used as internal standards (1H NMR signals
at δ 7.26 ppm and 2.49 ppm, respectively). The fluorescence
spectra were recorded on a Varian Cary Eclipse fluores-
cence spectrophotometer. Mass spectra were recorded on a
Shimadzu GCMS-QP2010SE gas chromato-mass spectro-
meter with a system for direct introduction of sample into
the ion source (EI, 70 eV). Elemental analysis was
performed on an Analytik Jena multi EA 5000 instrument.
Melting points were determined in glass capillaries using a
PTP(M) apparatus. The reaction progress and purity of the
obtained compounds were controlled by TLC (Silufol U-254
plates, CHCl3 as eluent, visualization with iodine vapor in a
moist chamber). Solutions were prepared by using spectral
grade acetonitrile, perchlorates of d-block metals and
tetrabutylammonium salts (Sigma-Aldrich). Amines 1a–e
were obtained according to published procedures,15 while
amine 2e was obtained according to another literature method.8e
Synthesis of N-(anthracen-9-ylmethyl)-1Н-benzimid-
azol-2-amines 2a–d (General method). Glacial acetic acid
1-Allyl-N-(anthracen-9-ylmethyl)-1H-benzimidazol-
2-amine (2b). Yield 3.1 g (85%), light-yellow fibrous pre-
cipitate, mp 228–229°С (n-BuOH). IR spectrum, ν, cm−1:
1
3335 (NH), 1465 (C=C), 1360 (C–N). H NMR spectrum,
δ, ppm (J, Hz): 4.56 (2H, d, J = 4.8, CH2); 4.85 (1Н, d,
J = 17.3) and 4.96 (1Н, d, J = 10.2, =СН2); 5.54 (2H, d,
J = 4.6, CH2); 5.64–5.75 (1H, m, СH); 6.91 (1H, t, J = 7.5,
H Ar); 6.96–7.03 (2Н, m, H Ar, NH); 7.08 (1Н, d, J = 7.6,
H Ar); 7.36 (1Н, d, J = 7.7, H Ar); 7.46–7.55 (4H, m,
H Ar); 8.09 (2H, d, J = 8.4, H Ar); 8.42 (2H, d, J = 8.4,
H Ar); 8.60 (1H, s, H Ar). 13C NMR spectrum, δ, ppm:
39.5; 43.3; 107.8; 115.2; 116.0; 118.5; 120.4; 124.7; 125.1;
126.1; 127.2; 128.7; 130.0; 130.3; 131.1; 132.9; 134.7;
142.7; 154.5. Mass spectrum, m/z (Irel, %): 363 [M]+ (14),
191 [C14H9CH2]+ (100), 41 [CH2=CHCH2]+ (38). Found, %:
C 82.70; H 5.76; N 11.54. C25H21N3. Calculated, %: C 82.62;
H 5.82; N 11.56.
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Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
N-(Anthracen-9-ylmethyl)-1-[2-(diethylamino)ethyl]-
15°C, and maintained at that temperature for 3–4 h. The
precipitate that formed was filtered off, washed with
EtOH, and air-dried. The obtained 1-(anthracen-9-yl-
methyl)-N-(2-chlorophenyl)methanimine was recrystallized
from toluene. Yield 8.7 g (92%), bright-yellow fibrous
crystals, mp 178–179°С (toluene). IR spectrum, ν, cm−1:
1H-benzimidazol-2-amine (2c). Yield 3.6 g (85%), beige
fine crystalline precipitate, mp 167–168°С (2-PrOH).
1
IR spectrum, ν, cm−1: 3325 (NH), 1460 (C=C). H NMR
spectrum, δ, ppm (J, Hz): 0.32 (6H, t, J = 7.7, 2СН3); 1.99
(4Н, q, J = 7.7, 2СН2); 2.42 (2Н, t, J = 4.6, СН2); 3.86 (2Н,
t, J = 4.6, СН2); 5.51 (2Н, d, J = 5.4, СН2); 6.92 (1Н, t, J = 8.1,
H Ar); 6.99 (1Н, t, J = 8.1, H Ar); 7.13 (1Н, d, J = 7.7,
H Ar); 7.33 (1Н, d, J = 7.7, H Ar); 7.47–7.56 (4Н, m,
H Ar); 7.62 (1Н, t, J = 5.4, NH); 8.09 (2Н, d, J = 8.2,
H Ar); 8.41 (2Н, d, J = 8.2, H Ar); 8.60 (1Н, s, H Ar).
13C NMR spectrum, δ, ppm: 10.6; 38.8; 39.5; 46.5; 52.4;
107.4; 115.3; 118.5; 120.2; 124.4; 125.1; 126.2; 127.3;
128.8; 130.0; 130.1; 131.1; 135.1; 142.6; 155.5. Mass
spectrum, m/z (Irel, %): 422 [M]+ (6), 191 [C14H9CH2]+ (38),
86 [Et2NCH2]+ (100). Found, %: С 79.52; Н 7.20; N 13.28.
С28Н30N4. Calculated, %: С 79.58; Н 7.16; N 13.26.
1
1628 (C=N). H NMR spectrum, δ, ppm (J, Hz): 7.14–
7.23 (2H, m, H Ar); 7.28–7.46 (2Н, m, H Ar); 7.50–7.65
(4Н, m, H Ar); 8.07 (2Н, d, J = 8.4, H Ar); 8.64 (1Н, s,
H Ar); 8.77 (1Н, d, J = 8.4, H Ar); 9.61 (1Н, s, CH).
Found, %: С 79.81; Н 4.55; Cl 11.15; N 4.49. С21Н14ClN.
Calculated, %: С 79.87; Н 4.47; Cl 11.22; N 4.44.
Sodium borohydride (1.90 g, 50 mmol) was gradually
added to a stirred and heated (50–60°С) solution of
1-(anthracen-9-ylmethyl)-N-(2-chlorophenyl)methanimine
(6.32 g, 20 mmol) in 2:1 mixture of EtOH–DMF (50 ml).
The mixture was stirred at the same temperature for 1 h,
then diluted with hot H2O (200 ml), and the excess of
borohydride was destroyed by adding dilute AcOH. The
suspension was cooled to 5–10°C and maintained at that
temperature for 4–5 h, the precipitate of N-(anthracen-9-yl-
methyl)-2-chloroaniline was filtered off and recrystallized
from n-BuOH. Yield 5.1 g (81%), yellow fine crystalline
precipitate, mp 144–145°С. IR spectrum, ν, cm−1: 3261
(NH), 1617 (NH). 1H NMR spectrum, δ, ppm (J, Hz): 3.93
(1Н, t, J = 5.2, NH); 5.14 (2Н, d, J = 5.2, CH2); 7.10–7.21
(2H, m, H Ar); 7.25–7.37 (2Н, m, H Ar); 7.46–7.58 (4Н,
m, H Ar); 8.05 (2Н, d, J = 9.0, H Ar); 8.20 (1Н, d, J = 9.0,
H Ar); 8.51 (1Н, s, H Ar). Found, %: С 79.27; Н 5.15;
Cl 11.25; N 4.33. С21Н16ClN. Calculated, %: С 79.36; Н 5.07;
Cl 11.16; N 4.41.
N-(Anthracen-9-ylmethyl)-1-[2-(piperidin-1-yl)ethyl]-
1H-benzimidazol-2-amine (2d). Yield 3.5 g (81%),
light-yellow fine crystalline precipitate, mp 174–175°С
(2-PrOH). IR spectrum, ν, cm−1: 3320 (NH), 1460 (C=C),
1360 (C–N). 1H NMR spectrum, δ, ppm (J, Hz): 0.10–0.20
(4H, m, 2СН2); 0.40–0.65 (2H, m, СН2); 1.78–2.06 (4Н, m,
2СН2); 2.36–2.52 (2Н, m, СН2); 3.77–3.93 (2Н, m, СН2);
5.67 (2Н, d, J = 3.6, СН2); 6.94–7.08 (2H, m, H Ar); 7.18
(1H, d, J = 7.7, H Ar); 7.38 (1H, d, J = 7.7, H Ar); 7.51–
7.70 (5H, m, H Ar, NH); 8.11 (2H, d, J = 8.2, H Ar); 8.43
(2H, d, J = 8.2, H Ar); 8.63 (1H, s, H Ar). 13C NMR spectrum,
δ, ppm: 23.2; 24.2; 39.0; 39.9; 54.0; 58.2; 107.5; 115.2;
118.5; 120.3; 124.4; 125.1; 126.2; 127.4; 128.8; 129.8;
130.3; 131.1; 135.1; 142.6; 155.3. Mass spectrum, m/z (Irel, %):
434 [M]+ (7), 191 [C14H9CH2]+ (28), 98 [(CH2)5NCH2]+
(100). Found, %: С 80.10; Н 6.98; N 12.92. С29Н30N4.
Calculated, %: С 80.15; Н 6.96; N 12.89.
N-(Anthracen-9-ylmethyl)-2-chloroaniline (4.75 g,
15 mmol) was dissolved in anhydrous toluene (50 ml), then
anhydrous pyridine (2.4 ml, 30 mmol) was added; the mixture
was vigorously stirred and treated with a solution of freshly
distilled chloroacetyl chloride (1.6 ml, 20 mmol) in
anhydrous toluene (10 ml). The reaction mixture was
refluxed for 2.5–3 h, then cooled to 5°С, the obtained
precipitate of pyridine hydrochloride was filtered and washed
on filter with toluene (2×5 ml). The filtrate was washed with
water (2×20 ml), dried over anhydrous Na2SO4, and the
solvent was removed at reduced pressure. The residue was
recrystallized from n-BuOH, giving acetamide 5. Yield 4.9 g
(84%), pale-green coarse-grained crystalline precipitate,
mp 157–159°С (n-BuOH). IR spectrum, ν, cm−1: 1671
2-Chloro-N-(quinolin-8-yl)acetamide (3). A solution
of freshly distilled chloroacetyl chloride (5.7 ml, 72 mmol)
in anhydrous toluene (25 ml) was added to a stirred
solution of quinolin-8-amine (8.65 g, 60 mmol) in
anhydrous toluene (50 ml) containing anhydrous pyridine
(7.3 ml, 90 mmol). The obtained solution was refluxed for
1–1.5 h, cooled to 5°С, the obtained precipitate of pyridine
hydrochloride was filtered and washed on filter with
toluene (3×10 ml). The filtrate was washed with water
(4×25 ml), dried over anhydrous Na2SO4, and evaporated at
reduced pressure. The residue was recrystallized from
2-PrOH. Yield 9.5 g (72%), white fine crystalline
precipitate, mp 133–134°С. IR spectrum, ν, cm−1: 3174 (NH),
1
(C=O). H NMR spectrum, δ, ppm (J, Hz): 4.07 (2Н, s,
CH2); 6.11 (2Н, s, CH2); 7.12–7.25 (2H, m, H Ar); 7.30–7.41
(2Н, m, H Ar); 7.50–7.63 (4Н, m, H Ar); 8.07 (2Н, d, J = 8.7,
H Ar); 8.23 (2Н, d, J = 8.7, H Ar); 8.55 (1Н, s, H Ar). Found,
%: С 70.15; Н 4.41; Cl 17.89; N 3.50. С23Н17Cl2NO.
Calculated, %: С 70.06; Н 4.35; Cl 17.98; N 3.55.
1
1674 (C=O), 1641 (C=N). H NMR spectrum, δ, ppm
(J, Hz): 4.31 (2H, s, СН2); 7.40–7.63 (3Н, m, H Ar); 8.17
(1Н, d, J = 8.3, H Ar); 8.68–8.80 (1Н, m, H Ar); 8.83–8.91
(1Н, m, H Ar); 10.90 (1Н, s, NH). Found, %: С 59.95;
Н 4.04; Cl 16.00; N 12.80. С11Н9ClN2O. Calculated, %:
С 59.88; Н 4.11; Cl 16.07; N 12.70.
Synthesis of acetamides 4, 6c,e (General method). The
appropriate amine 1c,e, or 2c (3.0 mmol) was dissolved in
1,2-dichlorobenzene (10 ml), the solution was heated to
80–90°С and treated with N-(anthracen-9-ylmethyl)-2-chloro-
N-(2-chlorophenyl)acetamide (5) (1.30 g, 3.3 mmol) in the
case of amines 1c,e or 2-chloro-N-(quinolin-8-yl)acet-
amide (3) in the case of amine 2с. The obtained solution
was refluxed for 2 h. The reaction mixture was then cooled,
N-(Anthracen-9-ylmethyl)-2-chloro-N-(2-chlorophenyl)-
acetamide (5). Glacial acetic acid (0.1 ml) and 2-chloro-
aniline (3.5 ml, 33 mmol) were added to a solution of
anthracene-9-carbaldehyde (6.20 g, 30 mmol) in n-BuOH
(70 ml). The mixture was refluxed for 4 h, evaporated
under reduced pressure to 20–25 ml volume, cooled to 10–
183

Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
the precipitate that formed was filtered off and thoroughly
References
washed on filter with anhydrous acetоne. The residue was
recrystallized from a 4:1 mixture of n-BuOH–DMF.
2-[(Anthracen-9-ylmethyl)amino]-1-[2-(diethylamino)-
ethyl]-3-[2-oxo-2-(quinolin-8-ylamino)ethyl]-1H-benzimid-
azol-3-ium chloride (4). Yield 1.6 g (82%), light-brown
fine crystalline precipitate, mp >240°С (decomp.). IR spec-
trum, ν, cm−1: 3321, 3212 (NH), 1686 (C=O), 1655 (C=N).
1H NMR spectrum, δ, ppm (J, Hz): 0.83 (6Н, t, J = 6.9,
2CH3); 2.65 (2Н, t, J = 6.3, CH2); 3.30 (4Н, q, J = 6.9,
2CH2); 4.30 (2Н, t, J = 6.3, CH2); 5.41 (2H, s, CH2); 5.84
(2H, d, J = 6.8, CH2); 7.15–8.05 (13Н, m, H Ar, NH); 8.21
(2Н, d, J = 8.8, H Ar); 8.50 (2Н, d, J = 8.8, H Ar); 8.74–
8.83 (2Н, m, H Ar); 8.85–8.92 (1Н, m, H Ar); 11.53 (1Н, s,
NH). Found, %: С 72.90; Н 6.04; Cl 5.60; N 13.00.
С39Н39ClN6O. Calculated, %: С 72.82; Н 6.11; Cl 5.51;
N 13.07.
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2-Amino-3-{2-[(anthracen-9-ylmethyl)(2-chlorophenyl)-
amino]-2-oxoethyl}-1-[2-(diethylamino)ethyl]-1H-benz-
imidazol-3-ium chloride (6c). Yield 1.7 g (91%), bright-
yellow crystals, mp >220°С (decomp.). IR spectrum, ν, cm−1:
1
3310, 3194 (NH2), 1683 (C=O), 1662 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 0.87 (6Н, t, J = 6.7, 2CH3); 2.72
(2Н, t, J = 6.5, CH2); 3.41 (4Н, q, J = 6.7, 2CH2); 4.27 (2Н,
t, J = 6.5, CH2); 4.55 (2H, s, CH2); 6.15 (2H, s, CH2); 7.05–
7.87 (12Н, m, H Ar); 8.14 (2Н, d, J = 8.7, H Ar); 8.40 (2Н,
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С36Н37Cl2N5O. Calculated, %: С 69.00; Н 5.95; Cl 11.31;
N 11.18.
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1
3294, 3178 (NH2), 1680 (C=O), 1652 (C=N). H NMR
spectrum, δ, ppm (J, Hz): 1.48 (6H, s, 2СН3); 1.58–1.73
(4Н, m, 2СН2); 4.01 (2Н, t, J = 6.5, СН2); 4.65 (2H, s,
CH2); 6.08 (2Н, d, J = 5.3, СН2); 7.12–7.95 (12Н, m,
H Ar); 8.24 (2Н, d, J = 8.5, H Ar); 8.48 (2Н, d, J = 8.5,
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on PES were found by the steepest descent method (along
gradient lines) from the saddle point to the adjacent
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The work was performed with financial support from the
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00439 mol_a).
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184

Chemistry of Heterocyclic Compounds 2017, 53(2), 179–185
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185