532
N. M. A. El-Ebiary et al.
Arch. Pharm. Chem. Life Sci. 2010, 9, 528–534
Gemini 200 MHz (Varian Inc., Palo Alto, CA, USA) in a suitable
deuterated solvent using TMS as an internal standard. The mass
spectra were recorded on GCMS-QP 1000Ex, Shimadzu spec-
trometer (Shimadzu, Japan) E.I. 70 eV at the Central Services
Laboratory, Faculty of Science, Cairo University and National
Research Centre, Cairo, Egypt. Samples were centrifuged using a
Heraeus Labofuge 400R (Kendro Laboratory Products GmbH,
Germany) and the spectrophotometric measurements were
recorded using Shimadzu UV-VIS Recording 2401 PC spectropho-
tometer (Shimadzu).
d6) d: 3.43–3.47 (br s, 5H, 3 OH þ H2O), 6.06 (d, 1H, J ¼ 8.7 Hz, H-6
trihydroxyphenyl), 6.56 (s, 1H, H-5 pyridine), 7.05 (d, 1H,
J ¼ 8.7 Hz, H-5 trihydroxyphenyl), 7.55–7.65 (m, 4H, chloro-
phenyl); MS m/z: 354 [Mþ] (100), 356 [Mþ þ 2] (30). Anal. calcd.
for C18H11ClN2O4: C, 60.94; H, 3.13; Cl, 9.99; N, 7.90. Found: C,
60.70; H, 3.30; Cl, 10.20; N, 8.10.
3-Cyano-4-(p-chlorophenyl)-6-(20,30,40-trimethoxyphenyl)-
2(1H)-pyridone 3b
Yield: 75%. M. p.: 259–2608C (ethanol); IR (film) n: 3310 (NH), 2211
(CN) cmꢀ1; 1H-NMR (DMSO-d6) d: 3.79, 3.86 (2s, 9H, 3 OCH3), 6.54
(s, 1H, H-5 pyridine), 6.93 (d, 1H, J ¼ 8.4 Hz, H-6 trimethoxy-
phenyl), 7.29 (d, 1H, J ¼ 8.8 Hz, H-5 trimethoxyphenyl), 7.60–
7.75 (m, 4H, chlorophenyl), 12.45 (s, 1H, NH); MS m/z: 398
General procedure for the synthesis of compounds 2a, b
To a solution of p-chlorobenzaldehyde (1.44 g, 0.01 mol), malo-
nonitrile (0.66 g, 0.01 mol), and ammonium acetate (6.16 g,
0.08 mol) in 25 ml ethanol (95%), compound 1a and/or 1b
(0.01 mol) was added. The reaction mixture was refluxed for
4–5 h. A solid product precipitated after cooling it was filtered
off, washed, and finally crystallized to afford 2a, b.
[Mþ ꢀ H] (100), 396 [Mþ þ 2
–
H], (30). Anal. calcd.
for C21H17ClN2O4: C, 63.56; H, 4.32; Cl, 8.93; N, 7.06. Found: C,
63.80; H, 4.50; Cl, 8.70; N, 7.30.
General procedure for the synthesis of 2-cyano-N0-[1-
ethylidene] acetohydrazide 4a, b
A mixture of compound 1a and/or 1b (.0.01 mol) and 2-cyano-
acetohydrazide (0.99 g, 0.01 mol) in absolute ethanol (50 mL) con-
taining few drops of concentrated sulfuric acid was stirred for 12 h
at room temperature. The solid that formed was filtered off,
washed with water several times, air dried, and crystallized from
the proper solvent to give the title compounds 11a, b, respectively.
2-Amino-4-(p-chlorophenyl)-6-(20,30,40-trihydroxyphenyl)
pyridine-3-carbonitrile 2a
Yield: 55%. M. p.: 2708C (decomposition) (ethanol); IR (film) n:
3381(OH), 3304, 3210 (NH2), 2212 (CN) cmꢀ1; 1H-NMR (DMSO-d6)
d: 3.1–3.7 (br s, 5H, 3 OH þ H2O), 6.9 (d, 1H, J ¼ 8.55 Hz, H-6
trihydroxyphenyl), 7.36 (s, 2H, NH2), 7.62–7.86 (m, 2H, p-chloro-
phenyl), 7.87 (d, 1H, J ¼ 8.6 Hz, H-5 trihydroxyphenyl), 8.1 (s, 1H,
H-5 pyridine), 8.4 (m, 2H, p-chlorophenyl) ppm; MS m/z: 353 [Mþ]
(3), 355 [Mþ þ 2] (1). Anal. calcd. for C18H12ClN3O3 (353.75): C,
61.11; H, 3.42; Cl, 10.02; N, 11.88. Found: C, 60.90; H, 3.70; Cl,
9.93; N, 12.10.
2-Cyano-N0-[1-(20,30,40-trimethoxyphenyl)ethylidene]aceto-
hydrazide 4a
Yield: 86%. M. p.: 239–2408C (methanol); IR (film) n: 3755, 3451,
3395(OH), 3254 (NH), 2260 (CN) and 1684 (CO) cmꢀ1 1H-NMR
;
(DMSO-d6) d: 2.26 (s, 3H, CH3), 3.92 (s, 2H, CH2), 6.32 (d, 1H,
J ¼ 7.5 Hz, H-6 phenyl), 6.93 (d, 1H, J ¼ 7.5 Hz, H-5 phenyl),
8.40, 9.27, 13.27 (3s, 3H, 3 OH), 11.15 (s, 1H, NH); MS m/z: 249
[Mþ] (25). Anal. calcd. for C11H11N3O4: C, 53.02; H, 4.44; N, 16.86.
Found: C, 52.88; H, 4.70; N, 16.36.
2-Amino-4-(p-chlorophenyl)-6-(20,30,40-trimethoxyphenyl)
pyridine-3-carbonitrile 2b
Yield: 65%. M. p.: 186–1888C (ethanol); IR (film) n: 3304, 3167
1
(NH2); 2198 (CN) cmꢀ1; H-NMR (DMSO-d6) d: 3.74, 3.77, 3.85 (3s,
9H, 3 OCH3), 6.93 (d, 1H, J ¼ 8.55 Hz, H-6 trimethoxyphenyl), 7.1
(s, 2H, NH2), 7.53 (d, 1H, J ¼ 8.85 Hz, H-5 trimethoxyphenyl),
7.59–7.66 (m, 5H, Ar-H and H-5 in pyridine); 13C-NMR (DMSO-
d6) d: 55.96, 60.52, 61.24 (3 OMe), 85.60 (CN), 107.98, 112.50,
116.96, 124.95, 125.36, 128.93, 130.12, 134.46, 135.94, 141.96,
152.17, 152.64, 154.76, 157.87, and 160.68 ppm (aromatic car-
bons). MS m/z: 395 [Mþ] (100), 397 [Mþ þ 2] (44.9). Anal. calcd.
for C21H18ClN3O3: C, 63.72; H, 4.58; Cl, 8.96; N, 10.62. Found: C,
64.10; H, 4.80; Cl, 9.10; N, 10.80.
2-Cyano-N0-[1-(20,30,40-trimethoxyphenyl)ethylidene]aceto-
hydrazide 4b
Yield: 87%. M. p.: 109–1118C (ethylacetate/n-hexane, 1:1); IR (film)
n: 3199 (NH), 2264 (CN), 1701 (CO) cmꢀ1 1H-NMR (DMSO-d6) d:
.
2.16 (s, 3H, CH3), 3.73, 3.74, 3.77 (3s, 9H, 3 OCH3), 4.07 (s, 2H, CH2),
6.78 (d, H, J ¼ 8.6 Hz, H-6 phenyl), 7.11 (d, J ¼ 8.6 Hz, 1H, H-5
phenyl), 10.86 (s, 1H, NH); MS m/z: 291 [Mþ] (39). Anal. calcd.
for C14H17N3O4: C, 57.73; H, 5.88; N, 14.43. Found: C, 57.64; H,
6.18; N, 14.80.
General procedure for the synthesis of compounds 3a, b
To a solution of a mixture of p-chlorobenzaldehyde (1.44 g,
0.01 mol), ethylcyanoacetate (1.13 g, 0.01 mol), and ammonium
acetate (6.16 g, 0.08 mol) in ethanol (25 mL, 95%), compound 1a
and/or 1b (0.01 mol) was added. The reaction mixture was
refluxed for 2–6 h. The solid product which formed while hot
was filtered off and crystallized to afford 3a, b.
6-Amino-4-(p-chlorophenyl)-3,5-dicyano-1-{[1-
(20,30,40- trimethoxyphenyl)ethylidene]-amino}-2(1H)-
pyridone 5
A mixture of compound 4b (2.91 g, 0.01 mol) and p-chloroben-
zylidine malononitrile (1.9 g, 0.01 mol) in ethanol (30 mL, 95%)
containing few drops of piperidine was refluxed for 15 min. The
solid that formed while hot was filtered off and recrystallized to
give 5 as colorless crystals (90% yield). M. p.: 278–2808C (meth-
3-Cyano-4-(p-chlorophenyl)-6-(20,30,40-trihydroxyphenyl)-
2(1H)-pyridone 3a
anol); IR (film) n: 3339, 3231 (NH2), 2210 (CN), 1657 (CO) cmꢀ1
;
Yield: 70%. M. p.: 2808C (decomposition) (ethanol); IR (film) n:
1H-NMR (DMSO-d6) d: 2.22 (s, 3H, CH3), 3.87, 3.88, 3.89 (3s, 9H, 3
OCH3), 6.92 (d, 1H, J ¼ 10.3 Hz, H-6 trimethoxyphenyl), 7.57–7.63
3445 (OH), 3132 (NH), 2215 (CN), 1662 (CO) cmꢀ1; 1H-NMR (DMSO-
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