Synthesis of 1-(1-aroyl-2-arylvinyl)-2-dicyanomethylen-1,2-dihydropyridines from 2-chloropyridinium salts and unsaturated nitriles

Article abstract of DOI:10.1023/A:1013240002478

1-(1-Aroyl-2-arylvinyl)-2-dicyanomethylene-1,2-dihydropyridines are formed from 1-(aroylmethyl)-2-chloropyridinium bromides and arylmethylenemalonitriles in ethanol at room temperature in the presence of a twofold excess of triethylamine. The products are converted into 2-amino-3-aroyl-1-cyanoindolizines on boiling in acetic acid.

Full text of DOI:10.1023/A:1013240002478

Chemistry of Heterocyclic Compounds, Vol. 37, No. 9, 2001
SYNTHESIS OF 1-(1-AROYL-
2-ARYLVINYL)-2-DICYANOMETHYLEN-
1,2-DIHYDROPYRIDINES FROM
2-CHLOROPYRIDINIUM SALTS
AND UNSATURATED NITRILES
G. E. Khoroshilov
1
-(1-Aroyl-2-arylvinyl)-2-dicyanomethylene-1,2-dihydropyridines are formed from 1-(aroylmethyl)-2-
chloropyridinium bromides and arylmethylenemalonitriles in ethanol at room temperature in the
presence of a twofold excess of triethylamine. The products are converted into 2-amino-3-aroyl-1-
cyanoindolizines on boiling in acetic acid.
Keywords: 1-(aroylmethyl)-2-chloropyridinium bromides, reactions with arylmethyleneindolonitriles,
1
-(1-aroyl-2-arylvinyl)-2-dicyanomethylene-1,2-dihydropyridines.
In a continuation of investigations, which are aimed at simple methods for the synthesis of
2
-dicyanomethylenepyridines [1, 2], it was found that 1-(aroylmethyl)-2-chloropyridinium bromides 1a-d
reacted with arylmethylenemalononitriles 2a-h in the presence of a twofold excess of a tertiary base to give
1
-(1-aroyl-2-arylvinyl)-2-dicyanomethylene-1,2-dihydropyridines 3a-j [3] (Table 1). The reactions occur under
mild conditions, probably via intermediate 4. The structures of compounds 3a-j have been confirmed by IR and
1
H NMR spectroscopy (Table 2).
CN
+
N
CN
CN
B:, EtOH
B:, EtOH
+
N
Cl
C
N
Cl + NC
_
_
_
R
–
Br
R
CN
CN
–Cl
R
R1
Br
O
R1
3a–j
O
R1
4
O
2
a–h
1
a–d
1
1
a R = C
6
H
5
H
, b R = 4-BrC
6
H
4
H
, c R = 4-ClC
6
H
4
, d 2-thienyl; 2 a R = 4-CH
3
OC
O)
6
C
H
4
H
,
1
1
1
1
b R = 3-FC
6
4
, c R = 4-FC
6
4
, d R = 3,4-(CH
3
O)
2
C
6
H
3
, e R = 2,4-(C
2
H
5
2
6
3
,
1
1
1
1
f R = 2-ClC
6
H
H
4
, g R = 2-furyl, h R = C
6
H
5
; 3 a R = C
6
H
5
, R = 4-CH
3
O)
OC
6
H
4
, b R = C
6
H ,
5
1
1
1
R = 3-FC
6
4
, c R = C
6
H
5
, R = 4-FC
6
H
4
, d R = C
6
H
5
H
, R = 3,4-(CH
, g R = 4-BrC
3
2
6
C H , e R = C
3
6
H ,
5
1
1
1
R = 2,4-(C
2
H
5
O)
2
C
6
H
3
, f R = C
6
H
5
, R = 2-ClC
6
4
6
H
4
, R = 4-FC
6
H ,
4
1
1
1
h R = 4-BrC
6
H
4
, R = 2-furyl, i R = 4-ClC
6
H
4
, R = 2-furyl, j R = 2-thienyl, R = C
6
H
5
; B = Et N
3
_
_________________________________________________________________________________________
Taras Shevchenko Lugansk State University, Lugansk 348011, Ukraine; e-mail: kgb@lgpi.lugansk.ua.
Translated form Khimiya Geterotsiklicheskikh Soedinenii, No. 9, 1245-1249, September 2001. Original article
submitted October 11, 1999.
0009-3122/01/3709-1141$25.00©2001 Plenum Publishing Corporation
1141

TABLE 1. Characteristics of Compounds 3a-j
Found, %
mp, °С
(recrystallisation
solvent)
Com-
Empirical
——————
Yield,
%
Calculated, %
pound formula
C
H
N
3
3
3
3
3
3
3
3
3
3
а
b
c
d
e
f
C
C
C
C
C
C
C
C
C
C
24
23
23
25
27
23
23
21
21
21
H
H
H
H
H
H
H
H
H
H
17
N
3
O
2
76.01
4.48
4.52
11.11
11.08
146-148 (EtOH)
184-186 (EtOH)
126-128 (EtOH)
222-224 (EtOH)
150-152 (BuOH)
189-191 (EtOH)
208-209 (BuOH)
240-242
88
87
89
73
74
59
64
83
77
82
7
5.97
14FN
14FN
3
O
75.22
3.87
11.41
7
5.19
3.84
11.44
3
O
75.23
3.82
3.84
11.46
11.44
7
5.19
19
23
N
3
3
O
3
3
73.31
4.71
10.29
7
3.34
4.68
10.26
N
O
74.09
5.31
5.30
9.64
9.60
7
4.12
71.93
1.97
14ClN
13BrFN
12BrN
12ClN
3
O
3.63
10.99
7
3.68
10.95
g
h
i
3
O
61.94
2.98
2.94
9.39
9.42
6
1.90
3
O
2
60.35
2.93
10.08
6
0.31
2.89
10.05
3
O
2
67.52
3.21
3.24
11.27
11.24
261-262 (dec.)
138-140 (EtOH)
6
7.48
j
13
N
3
OS
71.01
3.72
11.79
7
0.97
3.69
11.82
In addition the molecular structure of 1-[1-benzoyl-2-(2-furyl)vinyl]-2-dicyanomethylene-1,2-
dihydropyridine was investigated by X-ray crystallography [4].
1
TABLE 2. IR and H NMR Spectroscopic Data for Compounds 3a-j
Com-
pound
IR spectrum, ν, сm-1
1Н NMR spectrum, δ, ppm
C=N
C=O
C=C
1620
3
3
3
3
а
b
c
2157, 2180
2155, 2186
2154, 2184
2162, 2186
1633
3.80 (3H, s, OCH
.02-8.18 (13Н, m, 3-, 5-, 6-Н, С
6.85-8.07 (13Н, m, Py, C , C
.20 (1H, s, CH)
3
); 6.94 (1Н, s, 4-Н);
7
6
Н
4
, С
6
Н ,СН)
5
1653
1649
1652
1624
1621
1623
6
H
5
H
6 4
);
8
6.96 (1H, t, 4-Н); 7.13-8.10 (13Н, m, 3-, 5-, 6-H,
, С ); 17 (1Н, s, СН)
); 3.81 (3Н, s, OCH
.71-8.05 (12H, m, Py, C , C );
.79 (1H, s, CH)
С
Н
6 4
6
Н
5
d
3.58 (3Н, s, ОСН
3
3
);
6
6
H
5
H
6 3
7
3
e
2160, 2168
1650
1622
1.26 (6H, t, (CH
3
)
2
); 4.08 (4H, dd, (OCH ) );
2
2
2
185, 2195
6.64 (2H, d, C
6
2
H ); 6.98 (1H, t, 4-H);
7
8
.33-7.98 (9H, m, 3-, 5-, 6-H, C
6
H
1
, C
6
H );
5
.25 (1H, s, CH)
3
3
3
f
2152, 2180
2154, 2182
2158, 2187
1656
1654
1651
1620
1622
1624
6.90 (1H, t, 4-H); 6.93-8.12 (13H, m, 3-, 5-, 6-H,
, C , CH)
6.98 (1H, t, 4-H); 7.31-7.98 (12H, m, 3-, 5-, 6-H,
, C , CH)
C
6
H
4
6
H
5
g
h
C
H
6 4
6
H
4
6.74 (1H, dd, C
4
H
H
3
O); 6.92 (1H, t, 4-H);
O); 7.35 (1H, d, C O);
.73-7.92 (8H, m, 3-, 5-, 6-H, C , CH)
O); 6.94 (1H, t, 4-H);
O);
7
7
.17 (1H, d, C
4
3
4
H
3
6
H
4
3
3
i
2152, 2179
2162, 2192
1648
1656
1620
1624
6.72 (1H, dd, C
4
H
3
7
7
8
.15 (1H, d, C
4
H
3
O); 7.35 (1H, d, C
4
H
3
.75-8.01 (7H, m, 3-, 5-, 6-H, C
6
H );
4
.23 (1H, s, CH)
j
6.72-7.00 (4H, m, 4-H, C
4
H S); 7.20-8.10 (8H, m,
3
5
-, 6-, C , CH); 8.20 (1H, d, 3-H)
6
H
5
1
142

-1
The considerable decrease in the vibration frequencies of the cyano groups to 2152-2195 cm in the IR
spectra and the increase intensities in comparison with 2(1H)-dicyanomethylenepyrimidines (quinolines) [1, 5]
indicate that the bipolar resonance form 5 contributes to the structure of compounds 3.
CN
CN
_
+
N
2
1
R1
R
7
O
5
-1
The decrease in the frequencies of the keto groups to 1633-1656 cm [6] indicates a large amount of
1
conjugation in the α,β-unsaturated ketone unit. In the H NMR spectra the olefinic proton is shifted to low field
at 7.67-8.03 ppm which also confirmed conjugation of the double bond and the keto group. On the whole the
1
H NMR spectra are not in contradictory with suggested structure 3, however the basic part of signals were
overlapped by the resonances of the aromatic protons at 6.71-8.21 ppm.
It was predicted with high probability on the basis of the X-ray crystallographic results (an enforced
short nonbonding intramolecular contact C(7)···C(21) [2.797(4) Å] [4]) and spectroscopic studies (redistribution
of the electron density in molecules 3) that compounds 3 would undergo further cyclisation to the indolizines 6.
In fact when compounds 3c,g,i were boiled for a short time in acetic acid they gave 2-amino-3-aroyl-1-
1
cyanoindolizines 6a-c (route A) (in small yields because of insufficient solubility). The H NMR spectra and
characteristics of these compounds are given in Table 3.
CN
CN
A
AcOH
B
N
B:
CN
CN
+
+
Cl
R1
N
CN
NH2
N
R
_
R
Br
O
R
c,g,i
O
O
3
6
a–c
1
B = Et N
3
1
TABLE 3. Characteristics and H NMR Spectra of Compounds 6a-c
Found, %
1
Com-
Empirical
——————
mp, °С
Н NMR spectrum,
δ, ppm
Yield, %
A/B
Calculated, %
pound formula
(ethanol)
C
H
N
6
6
6
а
b
c
C
C
C
16
16
16
H
H
H
11
N
3
O
73.58 4.22 16.04 161-163
3.55 4.24 16.08
5.66 (2H, br. s, NH
2
);
32/90
43/94
41/96
7
6
7
7
9
.98 (1H, m, 7-H);
.50 (2H, dd, 5-, 6-H);
.58 (5H, s, C );
.16 (1H, d, 8-H)
H
6 5
10BrN
3
O
56.52 2.99 12.33 192-194
6.49 2.96 12.35
5.92 (2H, br. s, NH
2
);
5
7
7
7
9
.00 (1H, m, 7-H);
.55 (2H, dd, 5-, 6-H);
.68 (4H, dd, C );
.17 (1H, d, 8-H)
H
6 4
10ClN
3
O
65.01 3.44 14.17 199-201
4.98 3.41 14.21
5.88 (2H, br. s, NH
2
);
6
6
7
7
9
.97 (1H, dt, 7-H);
.48 (2H, dd, 5-, 6-H);
.60 (4H, s, C );
.14 (1H, d, 8-H)
H
6 4
1
143

The indolizines 6a-c were also obtained by direct synthesis from the pyridinium salts 1a-c and
malonodinitrile (route B) [7].
EXPERIMENTAL
1
IR spectra of nujol mulls were recorded with an IKS-29. H NMR spectra were recorded with a Bruker
WP-100 SY (100.13 MHz, internal standard TMS). Commercial DMSO-d was used as solvent without further
purification. Purity of the products was monitored by TLC (Silufol UV-254, 3:5 acetone–hexane).
-(1-Aroyl-2-arylvinyl)-2-dicyanomethylene-1,2-dihydropyridines (3a-j). Triethylamine (0.7 ml,
6
1
5
.0 mmol) was added with stirring to a suspension of a salt 1 (2.5 mmol) and an unsaturated nitrile 2 (2.5 mmol)
in ethanol (15-20 ml). The mixture was stirred for 3 h at 20°C. The precipitate was filtered off and washed with
ethanol and hexane. Where necessary it was recrystallized from a suitable solvent. Characteristics of the
products are cited in Tables 1 and 2.
2
-Amino-3-aroyl-1-cyanoindolizines (6a-c). A. A solution of a 1,2-dihydropyridine 3 (1.0 mmol) in
acetic acid (5 ml) was boiled for 5 min and kept for 1 day at 20°C. The precipitate was filtered off and washed
with ethanol and hexane.
B. Triethylamine (1.4 ml, 10.0 mmol) was added to a suspension of a salt 1 (5.0 mmol) and
malononitrile (0.4 g, 6.0 mmol) in ethanol (15 ml). The mixture was stirred at 20°C for 1 h, then kept for 1 day
in a refrigerator. The precipitate was filtered off, washed with ethanol and hexane, and recrystallized from
ethanol. Characteristics of the compounds obtained are cited in Table 3.
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1
2
3
.
.
.
Yu. A. Sharanin, G. E. Khoroshilov, A. M. Shestopalov, V. N. Nesterov, V. E. Shklover, V. P. Litvinov,
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(
1996).
I. A. Aitov and G. E. Khoroshilov, Abstracts. Ukr. Conf. "Chemistry of Nitrogen Heterocycles"
[
in Ukrainian], Kharkov (1997), 46.
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5
6
7
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V. N. Nesterov, Izv. Akad. Nauk, Ser. Khim., 181 (1998).
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1144