JOURNAL OF CHEMICAL RESEARCH 2015 151
was refluxed for about 5 h. After the completion of the reaction which
was monitored by TLC using chloroform:methanol (9:1), the solvent
was removed under reduced pressure. The resulting crude product was
washed with water (2×20 mL), dried and recrystallised from ethanol.
Ethyl N-(6-acetyl-4-cyano-2,5-diphenyl-2,5-dihydropyridazin-3-yl)-
formimidate (4a): Yellow crystals, yield 90%; m.p. 137–135 °C;
1H NMR (400 MHz, CDCl3) δ 1.15 (t, 3H, CH2CH3), 2.45 (s, 3H,
CH3–CO), 4.15 (q, 2H, O–CH2–), 5.05 (s, 1H, H‑5), 7.20–7.60 (m, 10H,
phenyl groups), 7.91 (s, 1H, N=CH–O); 13C NMR (100 MHz, CDCl3)
δ 14.2, 25.8, 38.8, 61.7, 105.8, 116.3, 122.4, 122.5, 125.2, 126.9, 127.0,
127.6, 127.7, 130.5, 132.8, 132.9, 141.3, 142.2, 149.3, 152.0, 166.9, 191.6;
MS (m/z)=372 (M+); IR (KBr) νmax/cm–1 3068, 2982, 2202, 1686, 1637,
1198, 759, 702. Anal. calcd for C22H20N4O2: C, 70.95; H, 5.41; N, 15.04;
found: C, 70.90; H, 5.39; N, 15.02%.
1191, 815, 615. Anal. calcd for C23H22N4O2: C, 71.48; H, 5.74; N, 14.50;
found: C, 71.27; H, 5.64; N, 14.45%.
Ethyl N-(6-acetyl-4-cyano-5-(4-methoxyphenyl)-2-phenyl-2,5-dihydro-
pyridazin-3-yl)formimidate (4g): Yellow crystals, yield 79%; m.p.
1
102–104 °C; H NMR (400 MHz, CDCl3) δ 1.15 (t, 3H, OCH2CH3),
2.45 (s, 3H, CH3–CO), 3.72 (s, 3H, OCH3), 4.15 (q, 2H, –O–CH2–),
5.04 (s, 1H, H‑5), 7.06–7.44 (m, 7H, phenyl groups), 7.72 (m, 2H,
phenyl group), 7.92 (s, 1H, N=CH–O); 13C NMR (100 MHz, CDCl3):
14.2, 25.7, 38.7, 55.1, 61.6, 105.8, 116.3, 122.4, 122.5, 127.3, 127.5,
130.4, 132.7, 132.8, 134.3, 142.1, 149.2, 152.0, 157.7, 166.8, 191.5; MS
(m/z)=402(M+); IR (KBr) νmax/cm–1 3027, 2223, 1605, 1571, 1513, 1278,
1183, 1025, 833, 612. Anal. calcd for C23H22N4O3: C, 68.64; H, 5.51; N,
13.92; found: C, 68.60; H, 5.48; N, 13.85%.
Synthesis of 4-aryl-5-hydrazinyl-3-(1-hydrazonoethyl)-1-phenyl-1,4-
dihydropyrimido[4,5-c]pyridazine 5a–e; general procedure
Ethyl N-(6-acetyl-5-(2-chlorophenyl)-4-cyano-2-phenyl-2,5-dihydro-
pyridazin-3-yl)formimidate (4b): Yellow crystals, yield 89%; m.p.
To a solution of each of the compounds 4a–e (10 mmol) in absolute
ethanol (20 mL), an excess amount of hydrazine hydrate (60 mmol,
1.50 g) was added and the solution was refluxed for 3–5 h. After
the completion of the reaction which was monitored by TLC using
chloroform–methanol (9:1), the resulting solid was filtered off,
washed with water, dried and recrystallised from ethanol.
5-Hydrazinyl-3-(1-hydrazonoethyl)-1,4-diphenyl-1,4-dihydro-
pyrimido[4,5-c]pyridazine (5a): Yellow crystals, yield 85%; m.p.
266–269 °C; 1H NMR (400 MHz, DMSO‑d6):δ 1.95 (s, 3H, CH3),
5.65 (s, 1H, H‑4), 5.75 (br s, 2H, NH2, D2O exchangeable), 6.60 (br s,
1H, NH, D2O exchangeable), 6.90 (s, 2H, NH2, D2O exchangeable),
7.11–7.60 (m, 10H, phenyl groups), 7.85 (s, 1H, H‑7); 13C NMR
(100 MHz, DMSO‑d6) δ 10.3, 36.2, 97.5, 114.7, 114.8, 125.9, 128.6,
128.8, 128.9, 129.1, 129.2, 129.3, 129.4, 136.3, 139.9, 141.9, 146.2,
153.9, 159.4, 166.1; MS (m/z)=372 (M+), 356(M+ –16), 341(M+ –31),
281(M+ –91), 77(M+ –295), 57(M+ –315); IR (KBr) νmax/cm–1 3403, 3321,
3272, 1633, 1594, 745, 695. Anal. calcd for C20H20N8: C, 64.50; H, 5.41;
N, 30.09; found: C, 64.49; H, 5.38; N, 30.05%.
4-(2-Chlorophenyl)-5-hydrazinyl-3-(1-hydrazonoethyl)-1-phenyl-
1,4-dihydropyrimido[4,5-c]pyridazine (5b): Cream‑coloured crystals,
yield 35%; m.p. 253–255 °C; 1H NMR (400 MHz, DMSO‑d6) δ 1.95(s,
3H, CH3), 5.66(s, 1H, H‑4), 5.76 (br s, 2H, NH2, D2O exchangeable),
6.61 (br s, 1H, NH, D2O exchangeable), 6.91 (brs, 2H, NH2, D2O
exchangeable), 7.20–7.64 (m, 9H, phenyl groups), 7.90 (s, 1H,
H‑7);13C NMR (100 MHz, DMSO‑d6) δ 9.7, 33.7, 91.2, 114.7, 114.8,
125.9, 127.0, 129.1, 129.2, 129.4, 129.8, 132.0, 135.9, 139.9, 140.0,
141.9, 147.3, 153.9, 159.3, 166.0; MS (m/z)=406(M+), 351(M+ –55),
319(M+ –87), 293(M+ –113), 210(M+ –196), 76(M+ –330), 57(M+ –349);
IR (KBr) νmax/cm–1 3428, 3387, 3313, 3224, 1591, 1495, 1447, 751. Anal.
calcd for C20H19ClN8: C, 59.04; H, 4.71; N, 27.54; found: C, 59.01; H,
4.57; N, 27.52%.
1
138–141 °C; H NMR (400 MHz, CDCl3) δ 1.16 (t, 3H, CH2CH3),2.45
(s, 3H, CH3–CO), 4.17 (q, 2H, –O–CH2–), 5.25 (s, 1H, H‑5), 7.21–7.58
(m, 9H, phenyl groups), 7.92 (s, 1H, N=CH–O);13C NMR (100 MHz,
CDCl3) δ 14.2, 25.8, 38.8, 61.7, 105.8, 116.3, 122.4, 122.5, 125.2,
126.8, 126.9, 127.4, 127.6, 130.5, 132.6, 132.8, 141.3, 142.2, 149.3,
152.0, 166.9, 191.6; MS (m/z)=406(M+), 359(M+ –47); IR (KBr) νmax
/
cm–1 3060, 2987, 2201, 1687, 1632, 1198, 757, 699. Anal. calcd for
C22H19ClN4O2: C, 64.94; H, 4.71; N, 13.77; found: C, 64.90; H, 4.69; N,
13.69%.
Ethyl N-(6-acetyl-5-(4-chlorophenyl)-4-cyano-2-phenyl-2,5-dihydro-
pyridazin-3-yl)formimidate (4c): Cream‑coloured crystals, yield 86%;
m.p. 140–142 °C;1H NMR (400 MHz, CDCl3) δ 1.16 (t, 3H, CH2CH3),
2.45(s, 3H, CH3–CO), 4.17 (q, 2H, –O–CH2–), 5.25(s, 1H, H‑5),
7.21–7.58 (m, 9H, phenyl groups), 7.92 (s, 1H, N=CH–O);13C NMR
(100 MHz, CDCl3) δ 14.2, 25.8, 38.8, 61.7, 105.8, 116.3, 122.3, 122.4,
125.2, 126.8, 126.9, 127.4, 127.6, 130.5, 132.7, 132.8, 141.3, 142.2,
149.3, 152.0, 166.9, 191.6; MS (m/z)=406(M+), 359(M+ –47); IR (KBr)
νmax/cm–1 3056, 2978, 2198, 1692, 1635, 1197, 763, 697. Anal. calcd for
C22H19ClN4O2: C, 64.94; H, 4.71; N, 13.77; found: C, 64.89; H, 4.70; N,
13.74%.
Ethyl N-(6-acetyl-4-cyano-5-(3-nitrophenyl)-2-phenyl-2,5-dihydro-
pyridazin-3-yl)formimidate (4d): Yellow crystals, yield 79%; m.p.
154–156 °C;1H NMR (400 MHz, CDCl3) δ 1.16 (t, 3H, CH2CH3),
2.45(s, 3H, CH3–CO), 4.17 (q, 2H, –O–CH2–), 5.25(s, 1H, H‑5),
7.21–7.58 (m, 9H, phenyl groups), 7.92 (s, 1H, N=CH–O);13C NMR
(100 MHz, CDCl3) δ 14.2, 25.8, 38.8, 61.7, 105.8, 116.3, 122.3, 122.4,
125.2, 126.7, 126.9, 127.5, 127.6, 130.5, 132.7, 132.8, 141.3, 142.2,
149.3, 152.0, 166.9, 191.6; MS (m/z)=417(M+), 340(M+ –77); IR (KBr)
νmax/cm–1 3109, 3060, 2982, 2198, 1696, 1636, 1594, 1571, 1350, 1198,
751, 694. Anal. calcd for C22H19N5O4: C, 63.30; H, 4.59; N, 16.78;
found: C, 63.28; H, 4.50; N, 16.74%.
4-(4-Chlorophenyl)-5-hydrazinyl-3-(1-hydrazonoethyl)-1-phenyl-
1,4-dihydropyrimido[4,5-c]pyridazine (5c): Yellow crystals, yield
38%; m.p. 265–267 °C; 1H NMR (400 MHz, DMSO‑d6) δ 1.95 (s,
3H, CH3), 5.65 (s, 1H, H‑4), 5.76 (br s, 2H, NH2, D2O exchangeable),
6.61 (br s, 1H, NH, D2O exchangeable), 6.91 (br s, 2H, NH2, D2O
exchangeable), 7.21–7.65 (m, 9H, phenyl groups), 8.03 (s, 1H,
H‑7);13C NMR (100 MHz, DMSO‑d6) δ 9.3, 36.2, 97.3, 114.7, 114.8,
125.9, 129.0, 129.1, 129.2, 129.3, 131.4, 131.3, 134.1, 136.4, 139.9,
141.9, 146.2, 153.9, 159.4, 166.1; MS (m/z)=406(M+), 388(M+ –18),
319(M+ –87), 292(M+ –114), 57(M+ –349); IR (KBr) νmax/cm–1 3409,
3297, 3223, 3109, 1592, 1489, 1440, 1303, 898. Anal. calcd for
C20H19ClN8: C, 59.04; H, 4.71; N, 27.54; found: C, 58.99; H, 4.62; N,
27.50%.
5-Hydrazinyl-3-(1-hydrazonoethyl)-4-(3-nitrophenyl)-1-phenyl-1,4-
dihydropyrimido[4,5-c]pyridazine (5d): Orange crystals, yield 30%;
m.p. 242–245 °C; 1H NMR (400 MHz, DMSO‑d6) δ 1.94(s, 3H, CH3),
4.43 (br s, 2H, NH2, D2O exchangeable), 6.01 (s, 1H, H‑4), 6.94 (br s,
2H, NH2, D2O exchangeable), 7.23–7.69 (m, 9H, phenyl groups), 8.11
(s, 1H, H‑7), 8.69 (s, 1H, NH, D2O exchangeable);13C NMR (100 MHz,
DMSO‑d6) δ 9.7, 33.9, 91.6, 123.8, 124.0, 125.2, 125.3, 125.7, 128.6,
128.7, 129.1, 129.3, 139.5, 142.9, 146.5, 146.7, 149.8, 153.1, 156.0,
Ethyl N-(6-acetyl-4-cyano-5-(4-nitrophenyl)-2-phenyl-2,5-dihydro-
pyridazin-3-yl)formimidate (4e): Cream‑coloured crystals, yield
84%; m.p. 140–142 °C;1H NMR (400 MHz, CDCl3) δ 1.16 (t, 3H,
CH2CH3),2.45 (s, 3H, CH3–CO), 4.17 (q, 2H, –O–CH2–), 5.06 (s, 1H,
H‑5),7.16 (m, 1H, phenyl group), 7.44 (m, 2H, phenyl group), 7.61 (m,
2H, phenyl group), 7.71 (m, 2H, phenyl group), 8.09(m, 2H, phenyl
group), 7.92 (s, 1H, N=CH–O); 13C NMR (100 MHz, CDCl3): 14.2,
25.8, 38.8, 61.7, 105.8, 116.3, 122.3, 122.4, 126.2, 126.4, 129.6, 129.8,
130.5, 132.6, 132.8, 142.2, 145.6, 146.9, 149.3, 152.0, 166.9, 191.6; MS
(m/z)=417(M+), 340(M+ –77); IR (KBr) νmax/cm–1 3117, 3060, 2974,
2194, 1696, 1635, 1524, 1356, 1197, 698. Anal. calcd for C22H19N5O4: C,
63.30; H, 4.59; N, 16.78; found: C, 63.27; H, 4.54; N, 16.75%.
Ethyl N-(6-acetyl-4-cyano-2-phenyl-5-(p-tolyl)-2,5-dihydro-pyridazin-
3-yl)formimidate (4f): Yellow crystals, yield 75%; m.p. 127–129 °C;
1H NMR (400 MHz, CDCl3) δ 1.14 (t, 3H, OCH2CH3), 1.74 (s, 3H,
aromatic‑CH3), 2.45 (s, 3H, CH3–CO), 4.15 (q, 2H, –O–CH2–), 5.04(s,
1H, H‑5), 7.16–7.44 (m, 7H, phenyl groups), 7.70 (m, 2H, phenyl
group), 7.92 (s, 1H, N=CH–O); 13C NMR (100 MHz, CDCl3): 14.2,
22.4, 25.7, 38.7, 61.6, 105.8, 116.3, 122.4, 122.5, 127.4, 127.5, 130.4,
131.7, 131.8, 132.7, 132.8, 136.5, 139.6, 142.1, 149.2, 152.0, 166.8, 191.5;
MS (m/z) = 386(M+); IR (KBr) νmax/cm–1 3035, 2222, 1708, 1604, 1588,