Synthesis of 2-(3-furyl)-1H-benzimidazoles from 2-phenacyl-1H- benzimidazoles

Article abstract of DOI:10.1007/s10593-007-0215-6

C-Alkylation at the active methylene group of 2-phenacyl-1H-benzimidazoles with phenacyl bromides proceeds highly selectively with the formation of the corresponding 1,4-diketones, which on heating with hydrochloric acid are cyclized with the formation of the previously unknown 2-(2,5-diaryl-3-furyl)-1H- benzimidazoles.

Full text of DOI:10.1007/s10593-007-0215-6

Chemistry of Heterocyclic Compounds, Vol. 43, No. 11, 2007
SYNTHESIS OF 2-(3-FURYL)-
1H-BENZIMIDAZOLES FROM
2-PHENACYL-1H-BENZIMIDAZOLES
I.B. Dzvinchuk and M. O. Lozinskii
C-Alkylation at the active methylene group of 2-phenacyl-1H-benzimidazoles with phenacyl bromides
proceeds highly selectively with the formation of the corresponding 1,4-diketones, which on heating with
hydrochloric acid are cyclized with the formation of the previously unknown 2-(2,5-diaryl-3-furyl)-1H-
benzimidazoles.
Keywords: benzimidazoles, phenacyl bromides, furans, C-alkylation, selectivity, cyclocondensation.
2-(2-Furyl)benzimidazole possesses marked antimicrobial activity and has been intensively subject to
structural modification by chemists [1-10]. On the other hand its structural analogs with 3-furyl substituents are
little known, only two compounds of this type have been reported. The unsubstituted 2-(3-furyl)-benzimidazole
was synthesized from furan-3-carboxylic acid and its derivatives [11, 12] or from furan-3-carbaldehyde [13]. Its
derivative substituted with hydroxyl groups at positions 2 and 4 of the furan ring was obtained from the product
of C-acylation of (2-benzimidazolyl)acetonitrile with chloroacetyl chloride [14]. It is impossible to exclude that
the development of the practical usefulness of 2-(3-furyl)benzimidazoles will aid broadening of the series of
their representatives and the development of preparatively convenient and fairly general methods for their
synthesis. The chemical part of this problem is solved in the present work mainly by the conversions of
2-phenacyl-1H-benzimidazoles 1a-d, which have already recommended themselves as convenient reagents in
the synthesis of new compounds with a benzimidazole fragment [15, 16].
We have found that compounds 1a-d are alkylated at the active methylene group by phenacyl bromides
2a-d with the formation of 1,4-diketo compounds 3a-g. The obtained products on subsequent heating with
hydrochloric acid readily undergo cyclocondensation and give salts of the previously unknown 2-(3-furyl)benz-
imidazoles 4a-g (compound 4c was isolated as the better crystallizing hydrobromide), from which the free bases
5a-g were obtained after treatment with ammonia.
Such a scheme of synthesis was not obvious. It was shown previously that the direction of the acylation
reaction of 2-phenacyl-1H-benzimidazole 1a depends on the nature of the acylating reagent. With benzoyl
chloride dibenzoylation occurs with the participation of the nitrogen atom of the benzimidazole ring and the
oxygen atom of the phenacyl fragment [17]. With acetyl chloride monoacetylation occurs at the active methylene
group [18]. The selectivity of C-alkylation with phenacyl bromides, as we have established, depends on the
reaction conditions and is reduced on increasing the electron-withdrawing properties of the aryl substituents Ar
and Ar′ in the initial reactants. On interacting compounds 1a and 2a in boiling acetone over potassium carbonate
(under conditions typical of alkylating with bromoketones), in addition to the desired
__________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev 02094; e-mail:
Rostov@bpci.kiev.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1637-1645,
November, 2007. Original article submitted February 8, 2007.
1390
0009-3122/07/4311-1390©2007 Springer Science+Business Media, Inc.

Ar
Ar
BrCH2COAr1
O
N
O
N
2a-d
O
N
KOH,
Me2CO–H2O,
N
H
Ar1
H
40°C, 0.5 h
3a-g
1a–d
Ar
Ar
H
HCl–HOAc–H2O,
1.5 : 1 : 1
N
N
NH4OH
O
O
+
N
H
100°C,
0.3-1.5 h
N
Ar1
Ar1
H
–
X
4a-g
5a-g
1 a Ar = Ph, b Ar = 4-MeOC6H4, c Ar = 3,4,5-(MeO)3C6H2, d Ar = 4-BrC6H4; 2 a Ar1 = Ph,
b Ar1 = 3,4-(MeO)2C6H3, c Ar1 = 4-ClC6H4, d Ar1 = 3-O2NC6H4; 3–5 a Ar = Ar1 = Ph,
b Ar = 4-MeOC6H4, Ar1 = Ph, c Ar = 3,4,5-(MeO)3C6H2, Ar1 = Ph, d Ar = 4-BrC6H4, Ar1 = Ph,
e Ar = Ph, Ar1 = 3,4-(MeO)2C6H3, f Ar = Ph, Ar1 = 4-ClC6H4, g Ar = Ph, Ar1 = 3-O2NC6H4;
4 a, b, d–g X = Cl, c X = Br
diketone 3a the product of N-alkylation 6 is also formed, which was successfully isolated, and which, as we
found, exists in solution in equilibrium with the tautomeric form 6′. The reaction becomes highly selective on
carrying it out in an aqueous acetone solution of potassium hydroxide (stronger base).
O
H
2a
Ph
N
N
3a
1a
+
K2CO3, Me2CO
COPh
6
O
Ph
N
N
DMSO-d6
6
COPh
6'
The desired products 3 were isolated from the reaction mixture in high yield (77-85%) in the majority of
examples without contamination by products of N-alkylation and purification was not required. An exception
was the alkylation of compound 1d containing the most electron-withdrawing aryl substituent (Ar = 4-BrC6H4)
in the series of reactants 1 used. The corresponding product 3 precipitated from the reaction mixture together
with the product of N-alkylation (1H NMR data) in 91% overall yield, and after purification by crystallization
was obtained in the pure state in 63% yield. Interaction of compound 1a with m-nitrophenacyl bromide 2d
readily gave a pure C-alkylation product 3g in satisfactory yield (50%), which is probably caused by undesired
consumption of the highly reactive bromo ketone on interacting with alkali.
The cyclocondensation of diketo compounds of type 3 with closure of the furan ring by a Paal-Knorr
reaction scheme occurs on heating in a mixture of hydrochloric and acetic acids in water at volume ratios of
1 : 1.5 : 1 and is complete after 1 h, uncomplicated by side reactions (such as cyclocondensation involving the
1391

AcOH – H 2O
100°C, 5 h
N
3a
O
N
H
Ph
7
Ph
N
Me2NCH(OMe)2
Py, 105°C, 4 h
O
5a
N
Ph
Me
8
TABLE 1. Characteristics of the Synthesized Compounds
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
mp, °С
Yield, %
С
Н
N
3a
3b
3c
3d
3e
3f
C23H18N2O2
C24H20N2O3
C26H24N2O5
C23H17BrN2O2
C25H22N2O4
C23H17ClN2O2
C23H17N3O4
C23H17ClN2O
C24H19ClN2O2
C26H23BrN2O4
C23H16BrClN2O
C25H21ClN2O3
C23H16Cl2N2O
C23H16ClN3O3
C23H16N2O
77.88
77.95
74.77
74.98
70.12
70.26
63.57
63.76
72.33
72.45
70.88
71.04
69.03
69.17
73.95
74.09
71.38
71.55
61.38
61.55
61.12
61.15
69.29
69.36
67.69
67.83
66.02
66.11
82.04
82.12
78.58
78.67
73.18
73.23
66.47
66.52
75.60
75.74
74.37
74.49
72.48
72.43
77.82
77.95
76.69
76.78
5.03
5.12
5.32
5.24
5.35
5.44
4.06
3.95
5.47
5.35
4.28
4.41
4.18
4.29
4.55
4.60
4.49
4.75
4.62
4.57
3.45
3.57
4.93
4.89
3.81
3.96
3.93
3.86
4.58
4.79
4.83
4.95
5.12
5.20
3.72
3.64
5.12
5.08
4.14
4.08
3.94
3.96
5.05
5.12
5.56
5.64
7.82
7.90
7.08
7.29
6.18
6.30
6.32
6.47
6.57
6.76
7.06
7.20
10.37
10.52
7.42
7.51
6.72
6.95
5.43
5.52
6.14
6.20
6.58
6.47
6.72
6.88
9.95
10.06
8.27
8.33
7.52
7.65
6.45
6.57
6.58
6.75
7.02
7.07
7.43
7.55
10.97
11.02
7.86
7.90
210.5-212
200-201.5
221.5-223
225-227.5
210-211.5
208-209.5
206.5-208
232-234
85
75
81
63
77
79
50
94
91
57
91
96
93
76
95
96
96
91
92
93
91
7
3g
4a
4b
4c
4d
4e
4f
226.5-228
219-221
271.5-273
214-215.5
226.5-228
223-224.5
215-217
4g
5a
5b
5c
5d
5e
5f
C24H18N2O2
C26H22N2O4
C23H15BrN2O
C25H20N2O3
C23H15ClN2O
C23H15N3O3
C23H18N2O2
C16H14N2O
228-229.5
225.5-227
271.5-273
215-216.5
187.5-189
259-260.5
138.5-140
5g
6
7
11.08
11.19
219-220.5
(229 [17])
86
8
C24H18N2O
82.18
82.26
5.07
5.18
7.86
7.99
153.5-155
85
1392

benzimidazole nitrogen atom). The desired compounds 4 and 5 were successfully isolated in yields mainly
exceeding 90%. It should be noted that mineral acid plays a significant role in the reaction. As we have
established, cyclization does not take place on heating compound 3a in a mixture of acetic acid and water, but
deacylation with the formation of 2-(β-benzoylethyl)-1H-benzimidazole 7 occurs. The C-alkylation carried out
by us is confirmed by this conversion, the more so since product 7 is a compound already described (obtained by
the condensation of β-benzoyl-propionic acid with o-phenylenediamine [19]). The structure of compound 5a was
also confirmed by a chemical conversion, by methylation at the benzimidazole nitrogen atom with the formation
of the corresponding derivative 8.
The composition and structures of the synthesized compounds were confirmed by data of elemental
analysis (Table 1) and 1H NMR spectra (Table 2).
In the 1H NMR spectra of compounds of type 3 the most convincing signals with regard to C-alkylation
being accomplished were the three doublets of doublets in the high field region, corresponding to the signal of
the protons of the diastereomeric methylene group and the neighboring methine group. On the other hand, in the
spectrum of the N-alkylation product 6 there were, corresponding to its structure, singlet signals of the phenacyl
methylene (6.12 ppm) and vinyl methine group
(6.36 ppm) , and also corresponding to tautomer 6′ singlet signals of two nonequivalent phenacyl methylene
groups (4.71 and 6.02 ppm). According to the ratio of the integral intensities of these signals the content of
tautomer 6′ amounted to ~8%. Signals are displayed in approximately in the same regions and in the same ratio
of integral intensities in the unpurified product 3d, together with its signals (see Table 2) and the signals of the
contamination by the N-alkylation product (~11%), which disappear after purification of the compound by
crystallization. The spectra of compounds of types 4, 5, 7, and 8 have no special features. The signal H-4′ of the
furan ring of the desired salts 4 is displayed at 7.55-7.95 and of their bases of type 5 at 7.36-7.82 ppm all
regularly displaced towards low field with the increase of electron-withdrawing properties of substituents Ar and
Ar′.
2-Phenacyl-1H-benzimidazoles are therefore highly selectively alkylated at the methylene group by
phenacyl bromides in an aqueous acetone solution of potassium hydroxide with the formation of the
corresponding 1,4-diketo compounds, which are fairly efficient reagents in the synthesis of the previously
unknown 2-(2,5-diaryl-3-furyl)-1H-benzimidazoles.
EXPERIMENTAL
A check on the progress of reactions and the purity of the synthesized compounds was carried out by
1
TLC on Silufol UV 254 plates in benzene–ethanol, 9:1, visualizing in UV light. The H NMR spectra were
recorded on a Bruker Avance DRX 500 (500 MHz) in DMSO-d6, standard was TMS. Before determining the
elemental analysis and spectral investigations of compound 6 it was dried for 24 h at 40-45oC, and the remaining
compounds were dried for 4-5 h at 125oC.
2-(1H-Benzimidazol-2-yl)-1,4-diphenylbutane-1,4-dione (3a). Bromo ketone 2a (0.440 g, 2.2 mmol)
was added during 5 min to a stirred solution of compound 1a (0.472 g, 2 mmol) and potassium hydroxide
(0.134 g, 2.4 mmol) in water (2 ml) and acetone (4 ml) at 40-45°C. Stirring was continued at the same
temperature for 25-30 min and the mixture then left to cool to 15-20°C. The solid was filtered off, washed with
water–acetone, 1 : 1, and dried. Product (0.604 g) was obtained, which was used without purification in
subsequent conversions.
Compounds 3b-g were obtained analogously from reactants 1a-d and the appropriate bromo ketone
2a-d. Compound 3d was recrystallized from pyridine–ethyl acetate, 1 : 2. IR spectrum, νC=O, cm-1: 1675 (3a),
1680 (3b), 1680 (3c), 1690 (3d), 1675 (3e), 1680 (3f), 1685 (3g).
1393

TABLE 2. 1H NMR Spectra of the Synthesized Compounds
Com-
pound
Chemical shifts, δ, ppm (J, Hz)
1
2
3a
3.75 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 4.23 (1H, dd, JH(A)-H(B) = 18.5,
JH-H(B) = 10.0, HB); 5.64 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH); 7.07-7.16 (2H, m,
H-5,6); 7.46-7.57 (6H, m, H-4,7 + 4 HPh-m); 7.62 and 7.67 (2 × 1H, two t,
J = 7.5, 2 HPh-m); 8.03 and 8.10 (2 × 2H, two d, J = 8.0, 4 HPh-o); 12.56 (1H, s, NH*)
3b
3c
3.67 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 3.81 (3H, s, H3CO); 4.24 (1H, dd,
JH(A)-H(B) = 18.5, JH-H(B) = 10.0, HB); 5.58 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH);
7.03 (2H, d, J = 7.5, 2 HAr-m); 7.04-7.15 (2H, m, H-5,6); 7.44 (1H, d, J = 7.5, H-7);
7.50 (1H, d, J = 7.5, H-4); 7.51 (2H, t, J = 8.0, 2 HPh-m); 7.66 (1H, t, J = 7.5, HPh-p);
8.02 and 8.08 (2 × 2H, two d, J = 8.0, 2 HAr-o and 2 HPh-o); 12.54 (1H, s, NH)
3.70 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 3.71 (3H, s, H3CO-p);
3.85 (6H, s, H3CO-m); 4.24 (1H, dd, JH(A)-H(B) = 18.5, JH-H(B) = 10.0, HB);
5.65 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH); 7.15 (2H, m, H-5,6); 7.42 (2H, s, 2 HAr);
7.45-7.57 (4H, m, H-4,7 + 2 HPh-m); 7.67 (1H, t, J = 7.0, HPh-p);
8.04 (2H, d, J = 8.0, 2 HPh-o); 12.58 (1H, s, NH)
3d
3e
3.77 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 4.23 (1H, dd, JH(A)-H(B) = 18.5,
JH-H(B) = 10.0, HB); 5.60 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH); 7.06-7.17 (2H, m,
H-5,6); 7.47-7.51 (2H, m, H-4,7); 7.55 (2H, t, J = 8.0, HPh-m); 7.67 (1H, t, J = 7.0, HPh-p);
7.74 (2H, d, J = 8.0, 2 HAr-m); 8.03 (4H, d, J = 8.0, 2 HAr-o + 2 HPh-o); 12.56 (1H, s, NH)
3.71 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 3.79 and 3.85 (2 × 3H, two s, 2 H3CO);
4.19 (1H, dd, JH(A)-H(B) = 18.5, JH-H(B) = 10.0, HB); 5.60 (1H, dd, JH-H(B) = 10.0,
JH-H(A) = 4.0, CH); 7.09 (1H, d, J = 7.5, HAr-5); 7.14 (2H, m, H-5,6); 7.45-7.48 (3H, m,
H-4,7 + HAr-2); 7.52 (2H, t, J = 8.0, HPh-m); 7.61 (1H, t, J = 7.0, HPh-p); 7.72 (1H, d,
J = 7.5, HAr-6); 8.08 (2H, d, J = 8.0, 2 HPh-o); 12.55 (1H, s, NH)
3f
3.73 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 4.22 (1H, dd, JH(A)-H(B) = 18.5,
JH-H(B) = 10.0, HB); 5.62 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH); 7.12 (2H, m, H-5,6);
7.48 (2H, m, H-4,7); 7.52 (2H, t, J = 8.0, HPh-m); 7.61-7.63 (3H, m, HPh-p + 2 HAr-m);
8.05 and 8.09 (2 × 2H, two d, J = 8.5 and J = 7.0, 2 HAr-o and 2 HPh-o); 12.57 (1H, s, NH)
3g
3.86 (1H, dd, JH(A)-H(B) = 18.5, JH-H(A) = 4.0, HA); 4.30 (1H, dd, JH(A)-H(B) = 18.5,
JH-H(B) = 10.0, HB); 5.67 (1H, dd, JH-H(B) = 10.0, JH-H(A) = 4.0, CH); 7.10-7.15 (2H, m,
H-5,6); 7.34-7.49 (2H, m, H-4,7); 7.52 (2H, t, J = 8.0, HPh-m); 7.62 (1H, m, HPh-p);
7.85 (1H, t, J = 7.0, HAr-5); 8.10 (2H, d, J = 8.0, HPh-o); 8.47 and 8.49 (2×1H, two d,
J = 8.0, HAr-4 and HAr-6); 8.72 (1H, s, HAr-2); 12.59 (1H, s, NH)
4a
4b
7.42 (1H, t, J = 7.5, H5'-Ph-p); 7.47-7.50 (7H, m, H-5,6 + 2 H5'-Ph-m + 3 H2'-Ph-p,-m);
7.67 (1H, s, H-4'); 7.75-7.80 (2H, m, H-4,7); 7.57-7.89 (4H, m, 4 HPh-o)
3.83 (3H, s, H3CO); 7.08 (2H, d, J = 7.5, 2 HAr-m); 7.40 (1H, t, J = 7.5, HPh-p);
7.48-7.54 (4H, m, H-5,6 + 2 HPh-m); 7.62 (1H, s, H-4'); 7.75-7.77 (2H, m, H-4,7);
7.83 (2H, d, J = 7.5, 2 HAr-o); 7.88 (2H, d, J = 7.5, 2 HPh-o)
4с
4d
4e
3.75 (3H, s, H3CO-p); 3.78 (6H, s, 2 H3CO-m); 7.31 (2H, s, 2 HAr-o); 7.43 (1H, t,
J = 7.5, HPh-p); 7.51-7.56 (4H, m, H-5,6 + 2 HPh-m); 7.61 (1H, s, H-4');
7.77-7.79 (2H, m, H-4,7); 7.89 (2H, d, J = 7.5, 2 HPh-o)
7.43 (1H, t, J = 7.5, HPh-p); 7.51-7.55 (4H, m, H-5,6 + 2 HPh-m); 7.69 (1H, s, H-4');
7.71 (2H, d, J = 7.5, 2 HAr-m); 7.78-7.80 (2H, m, H-4,7);
7.85-7.89 (4H, m, 2 HPh-o + 2 HAr-o)
3.65 and 3.75 (2 × 3H, two s, 2 H3CO); 7.09 (1H, d, J = 9.0, HAr-5);
7.38 (1H, s, HAr-2); 7.42 (1H, d, J = 9.0, HAr-6); 7.46-7.53 (5H, m, H-5,6 + 3 HPh-m,-p);
7.55 (1H, s, H-4'), 7.77-7.90 (2H, m, H-4,7); 7.85 (2H, d, J = 8.0, 2 HPh-o)
4f
7.50-7.54 (5H, m, H-5,6 + 3 HPh-m,-p); 7.60 (2H, d, J = 7.5, 2 HAr-m); 7.71 (1H, s, H-4');
7.78-7.80 (2H, m, H-4,7); 7.87-7.89 (4H, m, 2 HPh-o + 2 HAr-o)
4g
7.51-7.54 (5H, m, H-5,6 + 3 HPh-m,-p); 7.78-7.80 (2H, m, H-4,7); 7.82 (1H, m,
HAr-5); 7.91 (2H, d, J = 7.5, 2 HPh-o); 7.94 (1H, s, H-4'); 8.22 (1H, d, J = 7.5,
HAr-4); 8.30 (1H, d, J = 7.5, HAr-6); 8.58 (1H, s, HAr-2)
5a
5b
5c
7.22-7.24 (2H, m, H-5,6); 7.36-7.42 (2H, m, 2 HPh-p); 7.47-7.52 (5H, m,
4 HPh-m + H-7); 7.55 (1H, s, H-4'); 7.61 (1H, m, H-4); 7.88 (2H, d, J = 9.0,
2 H5'-Ph-o); 8.26 (2H, d, J = 9.0, 2 H2'-Ph-o); 12.74 (1H, s, NH*)
3.81 (3H, s, H3CO); 7.05 (2H, d, J = 8.5, 2 HAr-m); 7.21 (2H, m, H-5,6);
7.36 (1H, t, J = 7.5, HPh-p); 7.49-7.50 (3H, m, 2 HPh-m + H-7); 7.51 (1H, s, H-4'); 7.67 (1H,
m, H-4); 7.84 (2H, d, J = 7.5, 2 HPh-o); 8.28 (2H, d, J = 9.0, 2 HAr-o); 12.66 (1H, s, NH)
3.73 (3H, s, H3CO-p); 3.88 (6H, s, 2 H3CO-m); 7.20-7.26 (2H, m, H-5,6);
7.39 (1H, t, J = 7.5, HPh-p); 7.51-7.55 (3H, m, 2 HPh-m + H-7); 7.59 (1H, s, H-4');
7.64 (1H, m, H-4); 7.88 (2H, d, J = 7.5, 2 HPh-o); 8.01 (2H, s, 2 HAr-o); 12.72 (1H, s, NH)
1394

TABLE 2. (continued)
1
2
5d
5e
5f
7.23 (2H, m, H-5,6); 7.39 (1H, t, J = 7.5, HPh-p); 7.50-7.53 (3H, m, 2 HPh-m + H-7);
7.57 (1H, s, H-4'); 7.68 (3H, d, J = 7.0, H-4 + 2 HAr-m); 7.87 (2H, d, J = 7.0, 2 HPh-o);
8.31 (2H, d, J = 9.0, 2 HAr-o); 12.76 (1H, s, NH)
3.81 and 3.88 (2 × 3H, two s, 2 H3CO); 7.09 (1H, d, J = 9.0, HAr-5); 7.19-7.24 (2H, m,
H-5,6); 7.36-7.49 (6H, m, 2 HAr-o + 3 HPh-m,-p + H-4'); 7.52 (1H, d, J = 7.5, H-7);
7.67 (1H, d, J = 7.5, H-4); 8.25 (2H, d, J = 8.0, 2 HPh-o); 12.70 (1H, s, NH)
7.19-7.25 (2H, m, H-5,6); 7.40 (1H, t, J = 7.5, HPh-p); 7.46-7.48 (2H, m, HPh-m);
7.52 (1H, d, J = 7.5, H-7); 7.57 (2H, d, J = 7.0, HAr-m); 7.57 (1H, s, H-4');
7.68 (1H, d, J = 7.5, H-4); 7.88 (2H, d, J = 7.5, 2 HAr-o); 8.24 (2H, d, J = 7.5, 2 HPh-o);
12.70 (1H, s, NH)
5g
6
7.23 (2H, m, H-5,6); 7.42 (1H, t, J = 7.5, HPh-p); 7.48-7.51 (2H, m, HPh-m); 7.53 (1H, m,
H-7); 7.68 (1H, m, H-4); 7.78-7.81 (1H, m, HAr-5); 7.82 (1H, s, H-4'); 8.19 (1H, d, J = 7.5,
HAr-4); 8.27-8.30 (3H, m, HPh-o + HAr-6); 8.57 (1H, s, HAr-2); 12.74 (1H, s, NH)
4.71 (0.16H, s, CH2C-6'); 6.02 (0.16H, s, CH2N-6'); 6.12 (1.84H, s, CH2); 6.36 (0.92H,
s, CH); 7.12-7.22 (2H, m, H-5,6); 7.42-7.55 (4H, m, H-4,7 + 2 HPh-m);
7.61-7.77 (4H, m, 2 HPh-m + 2 HPh-p); 7.92 and 8.03 (1.84Н and 0.16Н, two d, J = 8.0,
2 HPh-o and 2 НPh-o-6'); 8.11 and 8.16 (0.16Н and 1.84Н, two d, J = 8.0, 2 НPh-o-6'
and 2 HPh-o); 12.25 (0.92H, s, NH)
7
8
3.18 (2H, t, J = 7.0, H2C-Het); 3.63 (2H, t, J = 7.0, H2C-CO); 7.09 (2H, m, H-5,6);
7.44 (2H, m, H-4,7); 7.52-7.55 (2H, m, 2 HPh-m); 7.63-7.66 (1H, m, HPh-p); 8.01 (2H, d,
J = 7.5, 2 HPh-o); 12.23 (1H, s, NH)
3.64 (3H, s, 1-CH3); 7.28 (1H, t, J = 7.5, H5'-Ph-p); 7.31-7.35 (2H, m, H-5,6);
7.37-7.40 (3H, m, 2 H2'-Ph-m + H-7); 7.44 (1H, s, H-4'); 7.49-7.52 (2H, m, H5'-Ph-m);
7.61-7.65 (3H, m, 2 H5'-Ph-o + H2'-Ph-p); 7.71 (1H, d, J = 8.5, H-4);
7.91 (2H, d, J = 7.5, H2'-Ph-o)
_______
*Subjected to deuterium exchange.
2-(3-Furyl-2,5-diphenyl)benzimidazolium Chloride (4a). A mixture of compound 3a (0.354 g,
1 mmol), glacial acetic acid (1.5 ml), water (1 ml), and concentrated hydrochloric acid (1 ml) was maintained at
100-105°C for 1 h. After cooling the reaction mixture, the solid formed was filtered off, washed with 2-propanol,
and dried. Analytically pure product (0.350 g) was obtained.
Compounds 4b-g were obtained analogously from compounds 3b-g respectively. To isolate bromide 4c
the reaction mixture was diluted with 48% hydrobromic acid (1 ml) before cooling.
2-(3-Furyl-2,5-diphenyl)-1H-benzimidazole (5a). A mixture of salt 4a (0.2 g), 20% aqueous ammonia
solution (0.5 ml), and pyridine (1.5 ml) was heated to boiling with stirring. Water (4 ml) was added dropwise
slowly to the boiling mixture during 2-3 min. After cooling, the solid was filtered off, washed with water, and
dried. Analytically pure product (0.17 g) was obtained.
Compounds 5b,d-g were obtained analogously from compounds 4b,d-g respectively. Products 5e,f
crystallized better if acetonitrile (2.5 ml) was used as solvent in place of pyridine.
2-[3-Furyl-5-phenyl-2-(3,4,5-trimethoxyphenyl)]-1H-benzimidazole (5c). A mixture of compound 3a
(0.444 g, 1 mmol), glacial acetic acid (1.5 ml), water (1 ml), and concentrated hydrochloric acid (1 ml) was
maintained at 100-105°C for 1 h. The reaction mixture was cooled to 40-45°C, diluted with acetone (2 ml) with
stirring, and made alkaline with 20% aqueous ammonia solution (5 ml). After cooling, the resulting solid was
filtered off, washed with water, and dried. Analytically pure product (0.411 g) was obtained.
2-[(2E)-2-Phenacyl-2,3-dihydro-1H-benzimidazol-2-ylidene]-1-benzoylethane (6). A mixture of
compound 1a (1.18 g, 5 mmol), bromo ketone 2a (1.19 g, 6 mmol), finely powdered potassium carbonate
(0.552 g, 4 mmol), and acetone (15 ml) was boiled with stirring for 2 h, then diluted with water (7.5 ml), and left
for 2 h slowly cooling to 15°C. The colorless solid compound 3a (1.26 g, 71%) was filtered off. A second solid
1395

separated from the filtrate left at 15°C for 2 h. The yellow solid was filtered off, washed with acetone–water, 1:1,
recrystallized from acetone–water, 2:1, and dried. Pure product 6 (0.132 g) was obtained. IR spectrum, νC=O, cm-
1: 1630, 1690.
2-(β-Benzoylethyl)-1H-benzimidazole (7). A mixture of compound 3a (0.354 g, 1 mmol), glacial acetic
acid (1.5 ml), and water (1 ml) was maintained at 100-105°C for 5 h. The reaction solution was cooled, diluted
with acetone (2 ml), and made alkaline by stirring in 20% aqueous ammonia solution (5 ml). The precipitate was
filtered off, washed with water, and recrystallized from pyridine–ethanol, 1:1. After drying, product 7 (0.215 g)
was obtained. IR spectrum, νC=O, cm-1: 1680 ( lit. 1685 [17]).
2-(3-Furyl-2,5-diphenyl)-1-methyl-1H-benzimidazole (8). A mixture of compound 5a (0.168 g,
0.5 mmol), DMF dimethylacetal (0.5 ml), and anhydrous pyridine (0.5 ml) was maintained at 105-110oC for 4 h.
The reaction solution was diluted with 2-propanol (1 ml) and water (3 ml), and heated with stirring until
crystallization began. After cooling, the solid was filtered off, washed with a mixture of 2-propanol–water, 1:1,
and dried. Analytically pure product (0.148 g) was obtained.
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