Activated anilide in heterocyclic synthesis
649
(CDCl3) δ 7.26–8.01 (m, 15H, arom-H and NH group), 2.4a 2-Amino-5-benzoyl-6-oxo-4-phenyl-1-(pyridin-
10.00 (s, 1H, NH); 13C NMR (CDCl3) δ 107.75, 3-yl)-1,4,5,6-tetrahydropyridine-3-carbonitrile (10a):
123.00, 124.70, 124.70, 124.95 125.25, 127.30, 128.90, Formed as white crystals (dioxane); 85% Yield; mp
128.90, 129.90, 129.90, 131.00, 131.00, 132.30, 243–245◦C; IR (KBr) 3250, 3194 (NH2), 3064 (CH-
133.90, 135.2, 137.50, 141.00, 144.45, 149.50, 152.00, arom), 2934 (CH-aliph), 2187 (CN), 1699 and 1654
158.50, 164.80. MS (m/z) 392 (M+), Anal. Calcd. for (C=O) cm−1;1H NMR (CDCl3) δ 4.25 (d, 1H, J = 6.6
C23H16N6O: C, 70.04; H, 4.11; N, 21.42; Found: C, Hz, H-4), 4.92 (d, 1H, J = 6.6 Hz, H-5), 7.26–8.14
69.97; H, 4.09; N, 21.27.
(m, 14H, aromatic H), 8.78 (s, 2H, NH2); 13C NMR
(CDCl3) δ 37.95, 68.60, 83.80, 115.40, 122.50,
126.80, 127.40, 127.40, 128.35, 129.2, 129.2, 129.60,
129.60, 131.70, 131.70, 135.30, 138.50, 140.00,
140.90, 141.35, 148.70, 157.40, 169.10, 194.70. Anal.
Calcd. for C24H18N4O2: C, 73.08; H, 4.60; N, 14.20;
Found: C, 73.02; H, 4.52; N, 14.16.
2.3b 1-(4-Chlorophenyl)-5-cyano-6-imino-4-phenyl-N-
(pyridin-3-yl)-1,6-dihydropyridazine-3-carboxamide
(7b): Formed as pale yellow crystals (ethanol); 57%
Yield; mp 188–190◦C; IR (KBr) 3315 and 3207 (NH),
3049 (CH-arom), 2206 (CN), 1648 (C=O) cm−1; H
1
NMR (CDCl3) δ 6.90–7.88 (m, 14H, arom-H and NH
group), 10.12 (s, 1H, NH); MS (m/z) 426 (M+); Anal.
Calcd. for C23H15ClN6O: C, 64.72; H, 3.54; Cl, 8.31;
N, 19.60; Found: C, 64.38; H, 3.50; Cl; 8.24; N, 19.55.
2.4b 2-Amino-5-benzoyl-4-(4-chlorophenyl)-6-oxo-1-
(pyridin-3-yl)-1,4,5,6-tetrahydropyridine-3-carbonitrile
(10b): Formed as white crystals (dioxane); 60%
Yield; mp 238–240◦C; IR (KBr) 3250, 3165 (NH2),
3050 (CH-arom), 2923 (CH-aliph), 2178 (CN), 1702
and 1685 (C=O) cm−1; 1H NMR (DMSO-d6) δ 4.32 (d,
1H, J = 8.1 Hz, H-4), 5.35 (d, 1H, J = 8.1 Hz, H-5),
7.42–8.61 (m, 13H, aromatic H), 8.62 (s, 2H, NH2);
MS (m/z) 428 (M+), Anal. Calcd. for C24H17ClN4O2:
C, 67.21; H, 4.00; Cl, 8.27; N, 13.06; Found: C, 67.17;
H, 3.95; Cl, 8.22; N, 13.01.
2.3c 5-Cyano-6-imino-4-phenyl-N-(pyridin-3-yl)-1-p-
tolyl-1,6-dihydropyridazine-3-carboxamide (7c):
Formed as red-brown crystals (ethanol); 54% Yield;
mp 170–172◦C; IR (KBr) 3272 and 3128 (NH),
1
2921(CH-aliph), 2197 (CN), 1626 (C=O) cm−1; H
NMR (CDCl3) δ 2.30 (s, 3H, Me); 7.10–7.92 (m, 14H,
arom-H and NH group), 9.87 (s, 1H, NH); Anal. Calcd.
for C24H18N6O: C, 70.92; H, 4.46; N, 20.68; Found: C,
70.89; H, 4.41; N, 20.61.
2.4c 2-Amino-5-benzoyl-4-(2-chlorophenyl)-6-oxo-1-
(pyridin-3-yl)-1,4,5,6-tetrahydropyridine-3-carbonitrile
(10c): Formed as white crystals (dioxane); 78%
Yield; mp 214–216◦C; IR (KBr) 3343, 3250 (NH2),
3073 (CH-arom), 2954 (CH-aliph), 2194 (CN), 1690
and 1655 (C=O) cm−1; 1H NMR (DMSO-d6) δ 4.62 (d,
1H, J = 6.6 Hz, H-4), 4.87 (d, 1H, J = 6.6 Hz, H-5),
7.27–8.68 (m, 13H, aromatic H), 8.75 (s, 2H, NH2);
Anal. Calcd. for C24H17ClN4O2: C, 67.21; H, 4.00; Cl,
8.27; N, 13.06; Found: C, 67.18; H, 3.95; Cl, 8.23; N,
13.02.
2.3d 5-Cyano-6-imino-1-(4-methoxyphenyl)-4-phenyl-
N-(pyridin-3-yl)-1,6-dihydro-pyridazine-3-carboxamide
(7d): Formed as red-brown crystals (dioxane); 58%
Yield; mp 178–180◦C; IR (KBr) 3300 and 3285 (NH),
3064 (CH-arom), 2921(CH-aliph), 2201 (CN), 1647
1
(C=O) cm−1; H NMR (CDCl3) δ 3.80 (s, 3H, MeO);
7.30–8.12 (m, 14H, arom-H and NH group), 10.22 (s,
1H, NH); MS (m/z) 424 (M++2); Anal. Calcd. for
C24H18N6O2: C, 68.24; H, 4.29; N, 19.89; Found: C,
68.11; H, 4.15; N, 19.70.
2.4d 2-Amino-5-benzoyl-4-(2,4-dichlorophenyl)-6-oxo-
1-(pyridin-3-yl)-1,4,5,6-tetrahydropyridine-3-carbonitrile
(10d): Formed as brown crystals (ethanol); 70%
2.4 General procedure for the synthesis
of tetrahydropyridine derivatives 10a–d
A mixture of propanamide derivatives 3 (10 mmol) and Yield; mp 140–142◦C; IR (KBr) 3349, 3337 (NH2),
arylidenemalononitriles 10a–d (10 mmol) in ethanol 3086 (CH-arom), 2960 (CH-aliph), 2210 (CN), 1680
1
(100 mL) containing catalytic amount of piperidine was and 1635 (C=O) cm−1; H NMR (DMSO-d6) δ 4.55
heated under reflux for 5 h. The reaction mixture was (d, 1H, J = 6.6 Hz, H-4), 4.79 (d, 1H, J = 6.6
allowed to cool and poured into crushed ice then acidi- Hz, H-5), 7.18–8.54 (m, 12H, aromatic H), 8.98 (s,
fied with HCl. The separated solid was filtered, washed 2H, NH2); MS (m/z) 465 (M++2), Anal. Calcd. for
with water and crystallized from the proper solvent to C24H16Cl2N4O2: C, 62.22; H, 3.48; Cl, 15.30; N, 12.09;
give the tetrahydropyridine derivative 10a–d.
Found: C, 62.18; H, 3.43; Cl, 15.25; N, 12.04.