Interaction of 2-chloroquinoline- 3-carbaldehydes with 2-hetaryl- acetonitriles

Article abstract of DOI:10.1007/s10593-010-0456-7

The interaction of 2-chloroquinoline-3-carbaldehydes with 1H-benzimidazol-2-ylacetonitriles and 1-benzyl-1H-imidazol-2-ylacetonitrile has been studied. It was shown that products of condensation at the methylene group are formed under mild conditions. Car

Full text of DOI:10.1007/s10593-010-0456-7

Chemistry of Heterocyclic Compounds, Vol. 45, No. 12, 2009
INTERACTION OF 2-CHLOROQUINOLINE-
3-CARBALDEHYDES WITH 2-HETARYL-
ACETONITRILES
T. A. Volovnenko1, A. V. Tarasov1*, R. I. Zubatyuk2,
O. V. Shishkin2, A. V. Turov1, and Yu. M. Volovenko1
The interaction of 2-chloroquinoline-3-carbaldehydes with 1H-benzimidazol-2-ylacetonitriles and
1-benzyl-1H-imidazol-2-ylacetonitrile has been studied. It was shown that products of condensation at
the methylene group are formed under mild conditions. Carrying out the reaction under more forcing
conditions leads to an intramolecular nucleophilic substitution of the chlorine atom and the formation
of cyclic ionic compounds (in the case of N-substituted hetarylacetonitriles), which are subsequently
dealkylated.
Keywords: (1-benzyl-1H-imidazol-2-yl)acetonitrile, 2-(1-benzyl-1H-imidazol-2-yl)-3-(2-chloroquino-
lin-3-yl)acrylonitrile, benzimidazo[1,2-a]benzo[g]-1,8-naphthyridine-6-carbonitriles, 1H-benzimidazol-
2-ylacetonitriles, benzo[g]imidazo[1,2-a]-1,8-naphthyridine-4-carbonitriles, 2-(1H-benzimidazol-2-yl)-
3-(2-chloroquinolin-3-yl)acrylonitriles,
5-alkyl-6-cyanobenzimidazo[1,2-a]benzo[g]-1,8-naphthyridi-
nium chlorides, 2-chloroquinoline-3-carbaldehydes.
We showed previously [1-4] that the interaction of (het)aromatic 2-haloaldehydes with hetaryl-
acetonitriles leads at the first stage to a condensation product of a type of Knoevenagel reaction, but
subsequently nucleophilic substitution of the halogen atom is accompanied by intramolecular cyclization with
the formation of new heterocyclic compounds.
In the present work we have studied the interaction of 2-chloroquinoline-3-carbaldehydes 1 with
1H-benzimidazol-2-ylacetonitriles 2 and 1-benzyl-1H-imidazol-2-ylacetonitrile 6. Only one example is known
of the reaction of 2-chloro-7-methylquinoline-3-carbaldehyde with 1H-benzimidazol-2-ylacetonitrile [5], as a
result of which a cyclic product possessing fluorescent properties was formed.
_______
* To whom correspondence should be addressed, e-mail: antaran@gala.net.
1Kiev T. Shevchenko National University, Chemical Faculty, Department of Organic Chemistry, Kiev 01601,
Ukraine.
2Scientific and Technological Corporation, Institute for Single Crystals, National Academy of Sciences of
Ukraine, Kharkiv 61001, Ukraine; e-mail: shishkin@isc.kharkov.com.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1847-1863, December, 2009.
Original article submitted April 30, 2009.
0009-3122/09/4512-1489©2009 Springer Science+Business Media, Inc.
1489

The reaction of 2-chloroquinoline-3-carbaldehydes 1 with 1H-benzimidazol-2-ylacetonitriles 2 under
mild conditions (heating in DMF at 90-95oC or boiling in 2-propanol) leads to condensation products at the
methylene group, 2-(1H-benzimidazol-2-yl)-3-(2-chloroquinolin-3-yl)acrylonitriles 3 (Table 1). The exception
R1
R
R
R1
NC
N
N
N
N
O
a or b, or c
R2
R3
+
R2
Cl
N
CN
R4
N
H
R4
R3
2a–c
1a–f
Cl
1
3a–n
a DMF, 90−95 °C, 1−2 h 30 min; b 2-PrOH, boiling, 10 min − 3 h; с MeOH, boiling, 10−20 min.
1 a−с R = R1 = H; а R2 = R3 = H, b R2 = Me, R3 = H; c R2 = R3 = Me, d R = R3 = Me, R1 = R2 = H;
e R = R2 = R3 = H, R1 = OMe; f R = R1 = R2 = H, R3 = OMe; 2 a R4 = H, b R4 = Me, c R4 = Bn;
3 a–g R1 = H, a R = R2 = R3 = R4 = H, b R = R4 = H, R2 = R3 = Me, c R2 = R4 = H, R = R3 = Me,
d R = R2 = R4 = H, R3 = OMe, e R = R2 = R3 = H, R4 = Me, f R = H, R2 = R3 = R4 = Me, g R2 = H,
R = R3 = R4 = Me, h–n R = H, h R1 = OMe, R2 = R3 = H, R4 = Me, i R1 = R2 = H, R3 = OMe,
R4 = Me, j R1 = R2 = R3 = H, R4 = Bn, k R1 = R3 = H, R2 = Me, R4 = Bn, l R1 = H, R2 = R3 = Me,
R4 = Bn, m R1 = OMe, R2 = R3 = H; R4 = Bn, n R1 = R2 = H, R3 = OMe, R4 = Bn
TABLE 1. Characteristics of Acrylonitriles 3
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °C*
Yield, %
Cl
N
3а
3b
3c
3d
3e
3f
С19H11ClN4
10.73
10.72
9.79
9.88
9.82
9.88
9.87
9.83
10.21
10.28
9.57
9.51
9.45
9.51
9.39
9.46
9.43
9.46
8.40
8.42
8.14
8.15
7.93
7.90
7.81
7.86
7.89
7.86
17.02
16.94
15.70
15.61
15.54
15.61
15.55
15.53
16.29
16.25
15.10
15.03
15.09
15.03
15.01
14.95
15.04
14.95
13.37
13.31
12.93
12.88
12.54
12.48
12.38
12.43
12.44
12.43
208
> 300
> 300
> 300
221
80
86
91
87
84
79
71
80
75
72
71
74
75
79
С21H15ClN4
С21H15ClN4
С20H13ClN4О
С20H13ClN4
С22H17ClN4
С22H17ClN4
С21H15ClN4О
С21H15ClN4О
С26H17ClN4
С27H19ClN4
С28H21ClN4
С27H19ClN4O
С27H19ClN4O
230
3g
3h
3i
204
227
237
3j
212
3k
3l
189
163
3m
3n
204
186
_______
*A heterocyclization reaction may occur on heating.
1490

was aldehyde 1a, the products of condensation of which 3a,e,j were obtained only on brief boiling in alcohol
(3a in methanol and 3e,j in 2-propanol). Carrying out the reaction in DMF involving aldehyde 1a gave a mixture
of condensation products and cyclic products.
1
The structure of compounds 3 is confirmed by the presence in the H NMR spectra (in DMSO-d6) of a
singlet for the H-4 proton of the quinoline nucleus at 8.88-9.29 and the styryl CH proton singlet at 8.12-8.62
ppm. In the case of compounds 3a-d a signal for the NH proton was also present with a chemical shift of
13.18-13.21 ppm. Assignment of the signals in the spectra of compounds 3 was made with the aid of
experiments on homonuclear (COSY, NOESY-1D) and heteronuclear (HMQC and HMBC) correlations using
product 3m as example (Fig. 1). A complete list of the heteronuclear correlations found is given in Table 2. In
the IR spectra of compounds 3 stretching vibrations were observed for the nitrile group in the 2207-2241 region,
and for the NH group at 3249-3317 cm-1 for compounds 3a-d (Table 3).
H7.34
H-4
7.81 H
H-5
120.6
123.4
129.7
H7.34
N
125.0
112.1
137.0
48.3
138.5
8.88
H
3.92
CH3
7.55
H
NC
H7.59
N
146.8
56.6
7.53
H-7
145.5
O159.1
128.4
128.4
H
107.2
138.5
H7.27
8.12
125.7
129.7
126.8
H
Cl
N 146.3
H
143.9
129.9
7.09
H
7.34
H
7.89
Fig. 1. Assignment of signals and Overhauser effects for compound 3m.
TABLE 2. Heteronuclear Correlations for Compound 3m (DMSO-d6)
Proton signals,
Chemical shifts of carbon signals with which there are correlations, δ, ppm
δ, ppm
HMQC
HMBC
8.88
8.12
7.89
7.81
7.59
7.55
7.53
7.34
138.5
145.5
129.9
120.6
112.1
107.2
125.7
146.3; 143.9; 107.2; 145.5
146.8; 146.3; 138.5; 116.1
159.1; 128.4
125.0
124.0
159.1
159.1
126.8;
137.0; 120.6
129.7; 112.1
129.7
125.0
123.4
7.27
7.09
5.83
3.92
128.4
126.8
48.3
126.8
48.3; 128.4
146.8; 137.0; 126.8
159.1
56.6
1491

TABLE 3. IR and 1H NMR Spectra of Compounds 3
1Н NMR spectrum, δ, ppm (J, Hz)*
IR,
spectrum
Com-
pound
H-4
quinoline
(1H, s)
CH=CCN
(1H, s)
ν
CN (νNH),
Characteristic signals
3
cm-1
1
2
4
5
3а
2230
(3249)
7.24-7.29 (2Н, m, H-5,6 benzimidazole);
7.50-7.52 (1Н, m, Н-7 benzimidazole);
7.70-7.73 (2Н, m, Н-6 quinoline,
8.60
9.09
Н-4 benzimidazole); 7.89 (1Н, t, J = 7.2,
Н-7 quinoline); 8.01 (1Н, d, J = 8.4,
Н-5 quinoline); 8.16 (1Н, d, J = 8.0,
Н-8 quinoline); 13.21 (1Н, s, NH)
3b
2241
2.50 (3Н, s, С-СН3); 2.68 (3Н, s, С-СН3);
7.23 (2Н, m, H-5,6 benzimidazole);
7.52 (2Н, d, J = 8.0, Н-6 quinoline,
H-7 benzimidazole); 7.68 (1Н, d, J = 7.2,
Н-4 benzimidazole); 7.85 (1Н, d, J = 8.4,
Н-5 quinoline); 13.18 (1Н, s, NH)
8.58
8.99
(3277)
3c
3d
3e
2224
2.68 (3Н, s, С-СН3); 2.74 (3Н, s, С-СН3);
7.23-7.28 (2Н, m, H-5,6 benzimidazole);
7.40 (1Н, d, J = 7.2); 7.53 (1Н, d, J = 7.2);
7.58 (1Н, d, J = 7.2); 7.68 (1Н, d, J = 8.0,
Н-7 quinoline); 13.20 (1Н, s, NH)
8.62
8.57
8.39
9.29
9.00
9.12
(3317)
2234
4.04 (3Н, s, О-СН3); 7.24-7.26 (2Н, m,
H-5,6 benzimidazole); 7.31 (1Н, d, J = 7.2,
Н-7 quinoline); 7.56-7.67 (4Н, m,
Н-5,6 quinoline, Н-4,7 benzimidazole);
13.21 (1Н, s, NH)
(3303)
2227
4.11 (3Н, s, N-СН3); 7.28-7.35 (2Н, m,
H-5,6 benzimidazole); 7.61 (1Н, d, J = 7.2,
Н-7 benzimidazole); 7.70-7.74 (2Н, m,
Н-6 quinoline, Н-4 benzimidazole);
7.90 (1Н, t, J = 7.2, Н-7 quinoline);
8.00 (1Н, d, J = 7.6, Н-5 quinoline);
8.16 (1Н, d, J = 7.2, Н-8 quinoline)
3f
2231,
2204
2.56 (3Н, s, С-СН3); 2.68 (3Н, s, С-СН3);
4.11 (3Н, s, N-СН3); 7.27 (1Н, t, J = 7.6,
benzimidazole); 7.33 (1Н, t, J = 7.6,
benzimidazole); 7.53 (1Н, d, J = 8.0,
Н-7 benzimidazole); 7.60 (1Н, d, J = 8.4,
Н-6 quinoline); 7.69 (1Н, d, J = 8.0,
Н-4 benzimidazole); 7.86 (1Н, d, J = 8.4,
Н-5 quinoline)
8.41
9.02
3g
3h
2207
2230
2.95 (3Н, s, С-СН3); 3.04 (3Н, s, С-СН3);
4.45 (3Н, s, N-СН3); 7.90-8.00 (5Н, m,
Н-6 quinoline, Н-4,5,6,7 benzimidazole);
8.18 (1H, d, J = 7.2, Н-7 quinoline)
8.78
8.68
10.32
9.82
4.12 (3Н, s, N-СН3); 4.39 (3Н, s, O-СН3);
7.83-7.94 (5Н, m, Н-5 quinoline,
Н-4,5,6,7 benzimidazole); 8.01 (1Н, d, J = 9.6,
Н-7 quinoline); 8.22 (1Н, d, J = 9.6,
Н-8 quinoline)
3i
3j
2231
2237
4.04 (3Н, s, N-СН3); 4.11 (3Н, s, O-СН3);
7.28-7.37 (3Н, m, Н-7 quinoline,
Н-5,6 benzimidazole); 7.60-7.67 (3Н, m,
Н-6 quinoline, Н-4,7 benzimidazole);
7.70 (1Н, d, J = 8.0, Н-5 quinoline)
8.39
8.14
9.04
9.00
5.81 (2Н, s, СН2Ph); 7.12 (2Н, d,
J = 7.2, H-2,6 Ph); 7.26-7.35 (5Н, m,
Н-5,6 benzimidazole, Н-3,4,5 Ph);
7.49-7.51 (1Н, m, H-7 benzimidazole);
7.69 (1Н, t, J = 7.2, Н-6 quinoline);
7.76-7.78 (1Н, m, H-4 benzimidazole);
7.87 (1Н, t, J = 7.2, Н-7 quinoline);
7.96 (1Н, d, J = 8.0, Н-5 quinoline);
8.11 (1Н, d, J = 8.4, Н-8 quinoline)
1492

TABLE 3 (continued)
1
2
3
4
5
3k
2234
2.61 (3Н, s, С-СН3); 5.77 (2Н, s, СН2Ph);
7.12 (2Н, d, J = 7.2, H-2,6 Ph);
8.14
8.96
7.26-7.36 (5Н, m, Н-5,6 benzimidazole,
Н-3,4,5 Ph); 7.49-7.52 (1Н, m,
H-7 benzimidazole); 7.54 (1Н, d,
J = 8.4, Н-6 quinoline); 7.77-7.79 (2Н,
m, Н-8 quinoline, Н-4 benzimidazole);
8.01 (1Н, d, J = 8.4, Н-5 quinoline)
3l
2230
2.54 (3Н, s, С-СН3); 2.65 (3Н, s, С-СН3);
5.81 (2Н, s, СН2Ph); 7.12 (2Н, d,
J = 7.2, H-2,6 Ph); 7.28-7.35 (5Н, m,
Н-5,6 benzimidazole, Н-3,4,5 Ph);
7.48-7.52 (2Н, m, Н-6 quinoline,
Н-7 benzimidazole); 7.76-7.78 (1Н, m,
H-4 benzimidazole); 7.81 (1Н, d,
J = 8.0, Н-5 quinoline)
8.17
8.91
3m
3n
2232
2230
3.92 (3Н, s, О-СН3); 5.83 (2Н, s, СН2Ph);
7.09 (1H, d, J = 7.2, H-2,6 Ph);
7.27-7.36 (5Н, m, Н-5,6 benzimidazole,
Н-3,4,5 Ph); 7.53-7.60 (3Н, m,
Н-5,7 quinoline, Н-7 benzimidazole);
7.81-7.82 (1Н, m, H-4 benzimidazole);
7.89 (1Н, d, J = 8.8, Н-8 quinoline)
8.12
8.14
8.88
8.91
4.02 (3Н, s, О-СН3); 5.82 (2Н, s, СН2Ph);
7.12 (2Н, d, J = 7.2, H-2,6 Ph);
7.28-7.35 (6Н, m, Н-6 quinoline,
Н-5,6 benzimidazole, Н-3,4,5 Ph);
7.48-7.50 (1Н, m, H-7 benzimidazole);
7.59-7.61 (2Н, m, Н-5,7 quinoline);
7.77-7.79 (1Н, m, H-4 benzimidazole)
_______
1
*The H NMR spectra were taken in DMSO-d6 (compounds 3a-f,i-n) and in deuterated
trifluoroacetic acid (compounds 3g,h).
Data of X-ray structural analysis of compound 3i indicate the formation of only one of the possible
isomers, just the E-isomer (Fig. 2).
Fig. 2. Molecular structure of compound 3i according to data of XSA. Ellipses of the thermal
vibrations of nonhydrogen atoms are shown at the 50% probability level.
1493

1494

The marked steric strain of the 3i molecule should be noted, linked with the presence of bulky
substituents at the central C=C double bond. This is indicated by the highly shortened intramolecular contacts at
C(7)···H(11) 2.55 and C(10)···H(14) 2.44 Å with the sum of the van der Waals radii at 2.87 Å [6], which lead to
distortion of the molecule [torsion angles N(2)–C(8)–C(9)–C(11) -24.0(3)o and C(9)–C(11)–C(12)–C(13)
22.6(4)o], and also to an increase of the valence angles C(11)–C(9)–C(10) 122.6(2)o and C(8)–N(2)–C(7)
129.85(18)o in comparison with the analogous angles C(10)–C(9)–C(8) 112.59(17)o and C(6)–N(2)–C(7)
123.04(18)o respectively.
The cyclic compounds 4 (Table 4), which we considered as models in subsequent investigations, were
synthesized from 2-chloroquinoline-3-carbaldehydes 1 and N-unsubstituted 1H-benzimidazol-2-ylacetonitrile 2a
under more forcing conditions (boiling in DMF). Compounds 4 (Table 4) may also be obtained in high yield
from the corresponding condensation products 3a-d. As mentioned above compound 4b was synthesized
previously in [5]. All the remaining products 4a,c-f are new substances.
R
1
R
H
R
C-8
C-7
CN
DMF, boiling
N
NC
DMF, boiling
CN
N
R2
1a–f
+
2
N
H
N
R
N
N-13
N
H
N
R3
R3
N
H
2a
C-1
Cl
3a–d
4a–f
4 a–d R1 = H, a R = R2 = R3 = H, b R = R3 = H, R2 = Me, c R = H, R2 = R3 = Me,
d R = R3 = Me, R2 = H, e, f R = R2 = H, e R1 = OMe, R3 = H, f R1 = H, R3 = OMe
1
A doublet for H-1 was observed at very low field in the H NMR spectra of compounds 4, the
anomalous chemical shift of which at 9.25-9.37 (DMSO-d6) or 9.90-9.92 ppm (TFA) is explained by the effect
of the electron pair of the N-13 atom. Singlets for H-7 and H-8 are frequently drawn together and are observed
at low field in the 8.81-9.16 (DMSO-d6) or 9.26-9.59 ppm (TFA) regions. In the IR spectra of products 4 an
intense band for the stretching vibrations of the CN group at 2227-2235 cm-1 was characteristic.
R
1
C-8
C-7
CN
N
R
a
a
2
R4
N
R
N
N-13
+
R3
–
Cl
C-1
1a–f
+
5a–h
3e–n
–R4Cl
b
2b,c
b
b
4a–f
a – DMF, boiling, 20 min − 1h 30 min; b – DMF, boiling, 3-12 h.
5 a-c R = R1 = H, a R2 = R3 = H, R4 = Me, b R2 = R4 = Me, R3 = H,
c R2 = R3 = R4 = Me, d R = R3 = R4 = Me, R1 = R2 = H, e–h R = H,
e R1 = OMe, R2 = R3 = H, R4 = Me, f R1 = R2 = H, R3 = OMe, R4 = Me,
g R1 = R3 = H, R2 = Me, R4 = Bn, h R1 = OMe, R2 = R3 = H, R4 = Bn
1495

On brief boiling of 2-chloroquinoline-3-carbaldehydes 1 with N-substituted 1H-benzamidazol-
2-ylacetonitriles 2b,c in DMF the ionic compounds 5 were obtained (Table 5) with the positive charge centered
on the nitrogen atoms and with Cl- anion as counter ion. Under similar conditions product 5 may also be
obtained with the same good yields from the appropriate compounds 3.
TABLE 5. 5-Alkyl-6-cyanobenzimidazo[1,2-a]benzo[g]-1,8-naphthyridi-
nium Chlorides 5 and 2-(1-Benzyl-1H-imidazol-2-yl)-3-(1-chloroquinolin-
3-yl)acrylonitriles 7
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °C*
Yield, %*2
Cl
N
5а
5b
5с
5d
5e
5f
C20H13ClN4
10.23
10.28
9.95
9.88
9.45
9.51
9.49
9.51
9.47
9.46
9.53
9.46
8.18
8.15
7.80
7.86
15.15
15.11
14.59
14.56
14.08
14.05
14.04
13.98
16.32
16.25
15.57
15.61
15.06
15.03
14.97
15.03
15.01
14.95
14.99
14.95
12.95
12.88
12.52
12.43
9.62
9.56
9.13
9.21
8.96
9.89
8.78
8.84
164
232
79
77
80
75
77
78
72
74
83
79
86
85
89
C21H15ClN4
C22H17ClN4
C22H17ClN4
C21H15ClN4O
C21H15ClN4O
C27H19ClN4
C27H19ClN4О
С22H15ClN4
С23H17ClN4
С24H19ClN4
С23H17ClN4О
С23H17ClN4О
275
> 300
> 300
238
5g
5h
7а
7b
7с
7d
7e
247
251
162
157
145
158
14.01
13.98
8.90
8.84
129
_______
*Heterocyclization may occur on heating compounds 7a-e.
*2The yield of compounds 5a-h is given for method A.
The disposition of the characteristic signals in the 1H NMR spectra of products 5 (Table 6) is analogous
to that in the spectra of cyclic compounds 4. However the H-1 doublet is displaced insignificantly towards low
field at 10.01-10.20 ppm (TFA). The H-7 and H-8 singlets were found in the 9.26-9.57 ppm (TFA) region and in
individual cases ran together into one signal. The presence of signals for the methyl (4.80-4.98 ppm) or benzyl
substituent (6.48 ppm for the CH2 group) at the N-5 atom is characteristic of the spectra of compounds 5. The
band for the stretching vibrations of the nitrile group was observed at 2207-2246 cm-1.
Subsequent investigations showed that as a result of the extended boiling of ionic compounds 5 in DMF
elimination of the substituent at atom N-5 occurs, as a result of which cyclic products are formed, the 1H NMR
spectra of which were identical to the spectra of model compounds 4.
We also proposed that in the elimination reactions the best leaving group is the benzyl substituent by
virtue of the greater stability of the benzyl cation. Confirmation of this is served by the shorter time needed to
carry out the elimination reaction and also the impossibility of isolating ionic compounds 5 in a pure state in
many stages in reactions with 1-benzyl-1H-benzimidazol-2-ylacetonitrile 2c.
1496

TABLE 6. IR and 1H NMR Spectra of Compounds 5
1Н NMR spectrum, δ, ppm (J, Hz)*
IR
Com-
pound
spectrum,
H-7 (1H, s),
Characteristic signals
H-1 (1H, d)
ν
CN, cm–1
H-8 (1H, s)
2246
4.80 (3Н, s, N–СН3); 8.00 (1Н, t, J = 7.2, Н-10);
8.12-8.15 (3Н, m, Н-2,3,4);
9.34,
9.39
10.05
(J = 8.0)
5а
8.31 (1Н, t, J = 8.0, Н-11);
8.37 (1Н, d, J = 8.4, Н-9);
8.60 (1Н, d, J = 8.4, H-12)
2231
2.91 (3Н, s, С–СН3); 4.84 (3Н, s, N–СН3);
7.92 (1Н, d, J = 8.4, Н-10);
9.36,
10.10
(J = 7.6)
5b
8.12-8.17 (3Н, m, Н-2,3,4);
8.31 (1Н, d, J = 8.8, Н-9); 8.46 (1Н, s, H-12)
2.84 (3Н, s, С–СН3); 3.16 (3Н, s, С–СН3);
4.80 (3Н, s, N–СН3); 7.87 (1Н, d, J = 8.4, Н-10);
8.10-8.16 (4Н, m, Н-2,3,4,9)
2230
2207
2235
9.29,
9.32
10.04
(J = 7.6)
5c
5d
5e
2.98 (3Н, s, С–СН3); 3.15 (3Н, s, С–СН3);
4.80 (3Н, s, N–СН3); 7.74 (1Н, d, J = 7.2, Н-10);
8.08-8.14 (4Н, m, Н-2,3,4,11)
9.40,
9.57
10.01
(J = 7.2)
4.38 (3Н, s, OСН3); 4.98 (3Н, s, N–СН3);
7.83 (1Н, s, H-9); 8.19 (1Н, d, J = 9.2, Н-11);
8.30-8.33 (3Н, m, Н-2,3,4);
9.44,
9.50
10.20
(J = 6.8)
8.69 (1Н, d, J = 9.2, H-12)
2231
2230
4.45 (3Н, s, OСН3); 4.83 (3Н, s, N–СН3);
7.77 (1Н, d, J = 8.4, Н-11);
7.94-8.02 (2Н, m, Н-9,10);
9.37,
9.40
10.12
(J = 6.8)
5f
8.15-8.19 (3Н, m, Н-2,3,4)
2.87 (3Н, s, С–СН3); 6.48 (2Н, s, СН2Ph);
7.31 (2Н, m, Н-2,6 Ph); 7.45 (3Н, m, Н-3,4,5 Ph);
7.88 (1Н, d, J = 8.4, Н-10);
9.33,
10.12
(J = 8.4)
5g
8.09-8.14 (3Н, m, Н-2,3,4);
8.27 (1Н, d, J = 8.8, Н-9); 8.44 (1Н, s, H-12)
4.18 (3Н, s, ОСН3); 6.48 (2Н, s, СН2Ph);
7.28-7.30 (2Н, m, Н-2,6 Ph);
2232
9.26,
9.33
10.08
(J = 8.4)
5h
7.43-7.45 (3Н, m, Н-3,4,5 Ph);
7.64 (1Н, s, H-9); 8.02–8.15 (4Н, m, Н-2,3,4,11);
8.52 (1Н, d, J = 9.2, H-12)
_______
*The 1H NMR spectra were taken in deuterated trifluoroacetic acid.
R1
H
N
N
NC
N
N
a
2
R
1a-c,e,f
+
CN
R3
N
H
Ph
Ph
Cl
6
7a–e
b
b
H
H
C-6
C-5
R1
R2
R1
CN
CN
2
R
–PhCH2Cl
N
N
N
–
N
N
N
+
R3
R3
Ph
C-1
Cl
9a–e
8
a – 2-PrOH, boiling, 30 min – 2h; b – DMF, boiling, 30 min – 1h;
7, 9 a R1 = R2 = R3 = H, b R1 = R3 = H, R2 = Me, c R1 = H, R2 = R3 = Me,
d R2 = R3 = H, R1 = OMe, е R1 = R2 = H, R3 = OMe
1497

We continued to study the processes of heterocyclization and elimination using the example of reactions
of 2-chloroquinoline-3-carbaldehydes 1 with 1-benzyl-1H-imidazol-2-ylacetonitrile 6.
H-4
H-5
H7.21
129.9
N
126.1
116.3
7.52
H
139.0
8.78
H
7.60
H
NC
N
140.4
50.6
7.60 H129.3
141.2
128.0
139.4
137.5
128.5
H
120.5
H7.32
7.80
111.9
129.6
127.1
H
7.32
Cl
N 147.7
H
139.0
154.8
7.10
H
7.37
O
H3C
3.96
56.6
Fig. 3. Assignment of signals and Overhauser effect for compound 7e.
TABLE 7. IR and 1H NMR Spectra of Compounds 7
1Н NMR spectrum, δ, ppm (J, Hz)*
IR
Com-
pound
spectrum,
CH=CCN
Н-4
Characteristic signals
ν
CN, cm1
(1H, s)
quinoline (1H, s)
7а
2230
5.56 (2Н, s, СН2–Ph);
7.88
8.85
7.13-7.15 (3Н, m, H-2,6 Ph, H-4 imidazole);
7.29–7.40 (4Н, m, H-3,4,5 Ph,
H-5 imidazole); 7.69 (1Н, t, J = 7.6,
H-6 quinoline); 7.84 (1Н, t, J = 7.6,
H-7 quinoline); 7.94 (1Н, d, J = 8.0,
H-5 quinoline); 8.07 (1Н, d, J = 8.0,
H-8 quinoline)
7b
7c
2227
2224
2.59 (3Н, s, СН3); 5.55 (2Н, s, СН2–Ph);
7.11-7.17 (3Н, m, H-2,6 Ph, H-4 imidazole);
7.28-7.39 (4Н, m, H-3,4,5 Ph, H-5 imidazole);
7.51 (1Н, d, J = 7.6, H-6 quinoline);
7.73 (1Н, s, H-8 quinoline);
7.86
7.87
8.80
8.75
7.95 (1Н, d, J = 8.0, H-5 quinoline)
2.51 (3Н, s, СН3); 2.63 (3Н, s, СН3);
5.55 (2Н, s, СН2–Ph);
7.12-7.15 (3Н, m, H-2,6 Ph, H-4 imidazole);
7.27-7.39 (4Н, m, H-3,4,5 Ph, H-5 imidazole);
7.48 (1Н, d, J = 8.4, H-6 quinoline);
7.77 (1Н, d, J = 8.4, H-5 quinoline)
7d
7e
2227
2224
3.94 (3Н, s, СН3); 5.56 (2Н, s, СН2–Ph);
7.13-7.15 (3Н, m, H-2,6 Ph, H-4 imidazole);
7.30-7.43 (6Н, m, H-5,7 quinoline,
H-3,4,5 Ph, H-5 imidazole);
7.86
7.80
8.73
8.78
7.82-7.84 (1Н, m, H-8 quinoline)
3.96 (3Н, s, СН3); 5.57 (2Н, s, СН2–Ph);
7.10 (2Н, d, J = 8.4, H-2,6 Ph);
7.21 (1Н, s, H-4 imidazole);
7.29-7.38 (4Н, m, H-3,4,5 Ph, H-7 quinoline);
7.52 (1Н, s, H-5 imidazole);
7.60-7.63 (2Н, m, H-5,6 quinoline)
_______
*The 1H NMR spectra were taken in DMSO-d6
1498

TABLE 8. Heteronuclear Correlations for Compound 7e (DMSO-d6)
Chemical shifts of carbon signals with which there are correlations
Proton signals, δ, ppm
HMQC
HMBC
8.78
7.80
7.61
139.4
141.2
154.8; 147.7; 141.2; 139.0; 120.5
147.7; 140.4; 139.0; 116.3; 120.5
129.3
120.5
154.8; 128.0
139.0
7.52
7.37
7.32
126.1
129.6
140.4; 129.9
137.5; 129.6; 127.1
111.9
128.5
139.0; 154.8; 120.5
127.1
7.21
7.10
5.57
3.96
129.9
127.1
50.6
140.4
129.6; 128.5; 127.1
140.4; 137.5; 127.1; 126.1
154.8
56.6
The condensation products 7 (Tables 5, 7) were obtained on interacting the initial compounds in boiling
1
2-propanol or on heating in DMF (90-95oC). In the H NMR spectra of these compounds the singlet of H-4 of
the quinoline nucleus, as in the spectra of condensation products 3, is observed at lowest field at 8.73-8.85 ppm.
The singlet of the styryl proton is found at lower field at 7.80-7.88 ppm. All assignments of signals were
carried out on the basis of investigations on homonuclear (COSY, NOESY-1D) and heteronuclear (HMQS and
HMBC) correlations using compound 7e as example (Fig. 3, Table 8).
In difference to reactions with 1H-benzimidazol-2-ylacetonitriles 2b,c, no ionic compounds 8 were
isolated even on brief boiling of the initial compounds 1 and 6 in DMF, since cyclic products 9 are formed at
once (Table 9) as a result of elimination of the benzyl substituent, and are derivatives of a new heterocyclic
system, viz. benzo[g]imidazo[1,2-a]-1,8-naphthyridine. Compounds 9 under analogous conditions were also
obtained from the appropriate products 7.
A characteristic of the 1H NMR spectra of the cyclic compounds 9 is the presence of three singlets in the
low field region corresponding to H-5 (8.50-8.62), H-1 (8.56-8.66), and H-6 (9.00-9.21 ppm) (Fig. 4). The
position of the characteristic signals was determined with the aid of experiments on homonuclear and
heteronuclear correlations using compound 9e as example (Table 10). In the IR spectra the band of the CN
group of the cyclic products 9 was observed at 2227-2235 cm-1 and was more intense than the band of the CN
group of condensation products 7 at 2224-2230 cm-1.
H-5
H-6
H-7
9.12
H
8.5H9
7.73
H
116.8
7.60 H127.4
127.8
103.2
CN
121.0
141.1
135.9
111.6
141.1
7.37
N
N 141.8
H
139.6
N
155.0
O
132.9
114.8
8.66 H
H3C
4.09
H 7.66
56.5
H-1
Fig. 4. Assignment of signals and Overhauser effect for compound 9e.
1499

1500

TABLE 10. Heteronuclear Correlations for Compound 9e (DMSO-d6)
Signals of protons,
Chemical shifts of carbon signals with which there are correlations
δ, ppm
HMQC
HMBC
9.12
8.66
8.59
7.73
7.66
7.60
7.37
4.09
141.1
114.8
135.9
121.0
132.9
127.4
111.6
56.5
155.0; 141.8; 139.6; 127.8; 121.0
141.1; 132.9
141.1; 141.8; 116.8; 115.4; 103.2
141.1; 139.6
141.1
155.0; 127.8
155.0
155.5
EXPERIMENTAL
1
The IR spectra were recorded on a Perkin-Elmer Spectrum BX instrument in KBr disks. The H NMR
spectra were measured on a Varian Mercury 400 spectrometer (400 MHz), in DMSO-d6 or deuterated
trifluoroacetic acid, internal standard was TMS. Experiments on NOE were carried out by the NOESY-1D
method, blending time 500 msec. The HMQC spectra were obtained for 128 experiments on 32 accumulations at
increments with spectral range of 4 kHz for protons and 21 kHz for carbon. Blending time corresponded to 1JCH
= 140 Hz. The HMBC spctra were obtained for 400 increments at 32 accumulations at increments of spectral
2-3
range 4 kHz for protons and 21 kHz for carbon. Blending time corresponded to
J
CH
= 8 Hz. Melting points
were measured on a microhot-stage of Boetius type with a PNMK 05 VEB Analytik eyepiece. A check on the
progress of reactions and the purity of the synthesized compounds was carried by TLC on Silufol UV 254 plates
in the system chloroform–methanol, 9:1.
X-Ray Structural Investigation of Compound 3i. Crystals of compound 3i were monoclinic, obtained
by slow crystallization from a hot solution of substance 3i in DMF. C21H15ClN4O, at 20oC: a = 11.6324(4),
b = 19.8026(9), c = 7.5798 (4) Å, β = 101.298(4)°, V = 1712.18(13) Å3, Mr = 374.82, Z = 4, space group P21/c,
dcalc = 1.454 g/cm3, µ(MoKα) = 0.24 mm-1, F(000) = 776. The parameters of the unit cell and the intensities of
16867 reflections (2921 independent, Rint = 0.046) were measured on an Xcalibur 3 automatic four-circle
diffractometer (MoKα, graphite monochromator, CCD detector, ω scanning, 2θmax = 50o). The structure was
solved by the direct method with the SHELX97 set of programs[7]. The positions of the hydrogen atoms were
made apparent from an electron density difference synthesis and refined with a rider model with Uiso = nUeq
(n = 1.5 for hydrogen atoms of methyl groups and n = 1.2 for the remaining hydrogen atoms). The structure was
refined on F2 by the full matrix least-squares method in an anisotropic approximation for the non-hydrogen
atoms to wR2 = 0.092 at 2921 reflections (R1 = 0.040 for 1907 reflections with F >4σ(F), S = 1.01). The
crystallographic data have been deposited in the Cambridge structural data bank (CCDC 726718).
Synthesis of 2-(1H-Benzimidazol-2-yl)-3-(2-chloroquinolin-3-yl)acrylonitriles 3f-i,k-n (General
Method). 2-Chloroquinoline-3-carbaldehyde 1b-f (2 mmol) was added to a solution of 1H-benzimidazol-
2-ylacetonitrile 2b,c (2 mmol) in DMF (2-3 ml) or in 2-propanol (5-7 ml) and the mixture heated on a boiling
water bath for 1 h to 2 h 30 min (in the case of 2-propanol boiled for 40 min to 3 h). The reaction mixture was
then cooled, the resulting solid was filtered off, washed with acetone, and dried.
Synthesis of 2-(1H-Benzimidazol-2-yl)-3-(2-chloroquinolin-3-yl)acrylonitriles 3a-e,j (General
Method). Compound 1 (2 mmol) was added to a solution of 1H-benzimidazol-2-ylacetonitrile 2a-c (2 mmol) in
2-propanol (5-7 ml), or in methanol (5-7 ml) for compound 3a, and the mixture boiled for 10-20 min (in the case
of compounds 3a-d) or 30 min to 1 h (in the case of compounds 3e,j). The reaction mixture was then cooled, the
resulting solid was filtered off, washed with acetone, and dried.
1501

Synthesis of Benzimidazo[1,2-a]benzo[g]-1,8-naphthyridine-6-carbonitriles 4a-f (General Method).
A. 2-Chloroquinoline-3-carbaldehyde 1 (2 mmol) was added to a solution of 1H-benzimidazol-2-ylacetonitrile
2a (2 mmol) in DMF (2-3 ml) and the mixture boiled for 30 min to 1 h 30 min. The reaction mixture was then
cooled, the resulting solid was filtered off, washed with acetone, and dried.
B. The appropriate product 3a-d (2 mmol) was dissolved in DMF (2-3 ml) and the solution boiled for
20 min to 1 h 30 min, then cooled. The resulting solid was filtered off, washed with acetone, and dried.
C. The appropriate 2-chloroquinoline-3-carbaldehyde 1 (2 mmol) was added to a solution of 1H-benz-
imidazol-2-ylacetonitrile 2b,c (2 mmol) in DMF (2-3 ml) and the mixture boiled for 3 to 12 h. The mixture was
then cooled, the resulting solid was filtered off, washed with acetone, and dried.
D. The appropriate product 3e-n (2 mmol) was dissolved in DMF (2-3 ml), and the mixture boiled for 3-12
h. After cooling, the resulting solid was filtered off, washed with acetone, and dried.
E. The appropriate product 5a-h (2 mmol) was dissolved in DMF (2-3 ml) and the mixture boiled for
3 to 12 h. After cooling, the resulting solid was filtered off, washed with acetone, and dried.
Synthesis of 5-Alkyl-6-cyanobenzimidazo[1,2-a]benzo[g]1,8-naphthyridinium Chlorides 5a-h
(General Method). A. The appropriate 2-chloroquinoline-3-carbaldehyde 1 (2 mmol) was added to a solution of
1H-benzimidazol-2-ylacetonitrile 2b,c (2 mmol) in DMF (2-3 ml) and the mixture boiled for 20 min to 1 h
30 min (in the case of compound 5a the reaction mixture was heated for 1-2 h on a boiling water bath). The
mixture was then cooled, the resulting solid was filtered off, washed with acetone, and dried.
B. The appropriate product 3 (2 mmol) was boiled in DMF (2-3 ml) for 20 min to 1 h 30 min (in the case
of compound 5a the reaction mixture was heated on a boiling water bath for 1-2 h). The reaction mixture was
then cooled, the resulting solid was filtered off, washed with acetone, and dried.
Synthesis of 2-(1-Benzyl-1H-imidazol-2-yl)-3-(2-chloroquinolin-3-yl)acrylonitriles 7a-e (General
Method). 2-Chloroquinoline-3-carbaldehyde 1 (2 mmol) was added to a solution of 1-benzyl-1H-imidazol-
2-ylacetonitrile 6 (2 mmol) in 2-propanol (5-7 ml) or in DMF (2-3 ml) and the mixture boiled for 30 min to 2 h
or in the case of DMF heated on a boiling water bath for 1 h to 1 h 30 min. After cooling the resulting solid was
filtered off, washed with acetone, and dried.
Synthesis of Benzo[g]imidazo[1,2-a]-1,8-naphthyridine-4-carbonitriles 9a-e (General Method). A.
The appropriate 2-chloroquinoline-3-carbaldehyde 1 (2 mmol) was added to a solution of compound 6 (2 mmol)
in DMF (2-3 ml) and the mixture boiled for 30 min to 1 h. The reaction mixture was cooled, and the resulting
solid filtered off, washed with acetone, and dried.
B. The appropriate product 7 (2 mmol) was dissolved in DMF (2-3 ml) and boiled for 30 min to 1 h. The
reaction mixture was then cooled, the resulting solid was filtered off, washed with acetone, and dried.
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3.
O. V. Khilya, T. A. Volovnenko, A. V. Turov, and Yu. M. Volovenko, Ukr. Khim. Zh., 69, No. 7-8, 55
(2003).
O. V. Khilya, T. A. Volovnenko, A. V. Turov, and Yu. M. Volovenko, Khim. Geterotsikl. Soedin., 1226
(2004). [Chem. Heterocycl. Comp., 40, 1063 (2004)].
O. V. Khilya, T. A. Volovnenko, and Yu. M. Volovenko, Khim. Geterotsikl. Soedin., 1520 (2006).
[Chem. Heterocycl. Comp., 42, 1311 (2006)].
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5.
6.
7.
T. A. Volovnenko, A. V. Tarasov, and Yu. M. Volovenko, Ukr. Khim. Zh., 72, No. 8, 108 (2006).
U. V. Gokhale and S. Seshadri, Dyes and Pigments, 8, 157 (1987).
Yu. V. Zefirov, Kristallografiya, 42, 936 (1997).
G. M. Sheldrick, Acta Crystallogr., A64, 112 (2008).
1502