Catalyst-free one-pot synthesis and antioxidant evaluation
2,6-Diamino-1-cyclohexyl-4-phenyl-1,4-dihydropyridine-3,5-dicarbonitrile (6a):
Dark Yellow crystals; mp 224–226 °C; IR (KBr) (ʋmax, cm−1): 3,352, 3,317 (NH2),
2,203 (CN), 1,096 (C–N); 1H NMR (400 MHz, CDCl3): δ (ppm) 1.22 (m, 4H, CH2),
1.50 (m, 2H, CH2), 1.72 (m, 4H, CH2), 2.48 (p, 1H, CH), 4.14 (s, 1H, CH), 5.92
(s, 2H, NH2), 7.25 (d, 2H, ArH, J = 7.8 Hz), 7.36 (t, 2H, ArH, J = 7.2 Hz), 7.37
(t, 1H, ArH, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3): δ (ppm) 24.53, 27.21,
32.04, 36.15, 57.01, 116.27, 125.42, 127.92, 130.21, 146.71, MS(ESI) m/z 320
(M + H)+; Anal. Calcd for C19H21N5: C, 71.45; H, 6.63; N, 21.93 %. Found: C,
71.40; H, 6.58; N, 21.90 %.
2,6-Diamino-4-(4-bromophenyl)-1-cyclohexyl-1,4-dihydropyridine-3,5-dicarbo-
nitrile (6e): Yellowish white crystals; mp 242–244 °C; IR (KBr) (ʋmax, cm−1):
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3,396, 3,338 (NH2), 2,220 (CN), 1,016 (C–N); H-NMR (400 MHz, CDCl3): δ
(ppm) 0.98 (m, 4H, CH2), 1.52 (m, 4H, CH2), 1.68 (m, 4H, CH2), 3.38 (m, 1H, CH),
4.12 (s, 1H, CH), 5.58 (s, 2H, NH2), 7.12 (d, 2H, ArH, J = 8.4 Hz), 7.58 (d, 2H,
ArH, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3): δ (ppm) 25.72, 31.64, 36.37,
50.77, 55.30, 83.83, 115.34, 125.59, 130.04, 132.32, 159.54, 166.70; MS(ESI) m/z
399 (M + H)+; Anal. Calcd for C19H20BrN5: C, 57.29; H, 5.06; N, 17.58 %. Found:
C, 57.22; H, 5.01; N, 17.55 %.
2,6-Diamino-1-cyclohexyl-4-(p-tolyl)-1,4-dihydropyridine-3,5-dicarbonitrile (6f):
Dark Yellow crystals; mp 238–240 °C; IR (KBr) (ʋmax, cm−1): 3,343, 3,312 (NH2),
2,210 (CN), 1,019 (C–N); 1H NMR (400 MHz, CDCl3): δ (ppm) 1.24 (m, 4H, CH2),
1.53 (m, 2H, CH2), 1.68 (m, 4H, CH2), 2.56 (p, 1H, CH), 3.83 (s, 1H, OCH3), 4.46 (s,
1H, CH), 5.73 (s, 2H, NH2), 6.89 (d, 2H, ArH, J = 8.0 Hz), 7.14 (d, 2H, ArH,
J = 8.0 Hz); 13C NMR (100 MHz, CDCl3): δ (ppm) 25.32, 27.10, 32.41, 36.30, 55.54,
57.62, 114.24, 116.05, 130.23, 134.63, 156.76, 161.36; MS(ESI) m/z 334 (M + H)+;
Anal. Calcd for C20H23N5: C, 72.04; H, 6.95; N, 21.00 %. Found: C, 71.95; H, 6.90; N,
20.89 %.
Results and discussion
To optimize the reaction conditions, initially we have tried the reaction of 4-
chlorobenzaldehyde (1b) with two equivalents of malononitrile (2) and n-
propylamine (3) in ethanol as a model reaction without any added catalysts. The
reaction proceeded smoothly even at room temperature resulting in the formation of
the target molecule (4b) with 58 % of yield in more than 5 h of reaction time. Then,
we tried the same reaction with various solvents and the best results were obtained
while using 60 % aqueous methanol as the solvent with a slight excess of amine.
In this reaction, the initial Knoevenagel condensation step might be promoted by
one of the excess reagents, namely, the n-propylamine (3) instead of using any other
external base as a catalyst. With these optimized reaction conditions, a variety of
substituted aromatic aldehydes (1a–i) have been utilized for the synthesis of a series
of 2,6-diamino-1-propyl-3,5-dicyano-1,4-dihydropyridine derivatives (Scheme 1).
The reactions of different aldehydes possessing either electron-withdrawing or
electron-donating substituents produced heterocyclic compounds with good yields,
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