66
F. M. Abdelrazek, S. A. Ghozlan, F. A. Michael
Vol 44
was found to be identical with an authentic sample obtained
from the reaction of 1 with elemental sulfur as described in the
literature for similar systems [5].
Anal. Calcd for (C18H12N2OS): C, 71.03; H, 3.97; N, 9.20; S,
10.54. Found: C, 70.80; H, 4.20; N, 9.50; S, 10.80.
solution of 2a (3.5 g; 0.01 mole) in 30 ml of ethanol was added
0.01 mole of cyanoacetamide, cyanoacetohydrazide, urea,
thiourea or guanidine nitrate followed by a conc. solution of
potassium carbonate (1.38 g, 0.01 mole, in the least amount of
water). The respective reaction mixtures were refluxed for 3 h,
left to cool, poured on cold water and neutralized with HC1. The
appearing precipitates were collected by filtration and
recrystallized to afford products.
Ethyl 3-Amino-4-benzoyl-6-cyano-5-phenyl-4H-thiopyran-
2-carboxylate (6). To a mixture of 3.5 g (0.01 mole) of 2a and
1.20 g (0.01 mole) of ethyl thioglycollate in 30 mL of ethanol
was added 1.64 g (0.02 mole) of sodium acetate. The mixture
was stirred at room temperature for 4 hours, then poured on ice-
cold water and neutralized with HC1. The formed dark-colored
precipitate was collected by filtration and recrystallized to afford
(2 g, 65%) of 6, brown crystalline solid, mp 175-176 °C (EtOH);
ir: ꢀmax (KBr) 3435-3235 (NH2), 2215 (CN), 1687 & 1708
(2C=O) cm-1, (m/e=390). 1H nmr (300 MHz, DMSO-d6): ꢁH 1.35
(t, J=7Hz, 3H, CH3), 4.15 (q, J=7Hz, 2H, CH2), 4.30 (s, 1H, 4-
H), , 7.15-7.90 (m, 10H, Ar. H), 8.25 (s, 2H, NH2 exch.); 13C
nmr: ꢁC 14.0(q), 55.5(d), 60.9(t), 99.8(s), 105.1(s), 116.2(s),
126.4(d), 127.8(d), 128.3(d), 128.5(d), 128.7(d), 133.2(d),
135.1(s), 137.6(s), 151.1(s), 152.4(s), 164.9(s), 195.4(s).
6-Amino-5-benzoyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-
carbonitrile (15). Dark yellow crystalline solid, mp 245-246 °C
(EtOH/DMF) (2.4 g, 78%); ir: ꢀmax (KBr) 3420-3220 (NH2 & NH),
1
2213 (CN), 1678 &1687 (2C=O) cm-1, (m/e=315); H nmr (300
MHz, DMSO-d6): ꢁH 7.10-7.80 (m, 10H, Ar. H), 8.2 (br. s, 2H,
NH2, exch.), 10.25 (s, 1H, NH exch.); 13C nmr: ꢁC 94(s), 95.5(s),
116.1(s), 124.9(s), 126.3(d), 127.5(d), 128.6(d), 129.1(d),
129.6(d), 134.2(d), 136.9(s) 152.0(s), 162.5(s), 169.1(s), 185.4(s).
Anal. Calcd for (C19H13N3O2): C, 72.37; H, 4.16; N, 13.3.
Found: C, 72.30; H, 4.50; N, 13.60.
4,7-Diamino-6-benzoyl-2-hydroxy-5-phenlylpyrrolo[1,2-b]-
pyridazine-3-carbonitrile (17). Brownish crystalline solid, mp
285-286 °C (EtOH/DMF) (2.6 g, ~70%); ir: ꢀmax (KBr) 3450-
3230 (NH2 & OH), 2218 (CN), 1682 (C=O) cm-1, (m/e=369); 1H
nmr (300 MHz, DMSO-d6): ꢁH 4.85 (s, 2H, NH2 exch.), 6.8 (s,
1H, OH exch.), 7.2-7.8 (m, 10H, Ar. H), 8.3 (s, 2H, NH2, exch.).
Anal. Calcd for (C21H15N5O2): C, 68.28; H, 4.09; N, 18.96.
Found: C, 68.20; H, 4.20; N, 19.30.
Anal. Calcd for (C22H18N2O3S): C, 67.67; H, 4.65; N, 7.17; S,
8.21. Found: C, 67.50; H, 4.90; N, 7.40; S, 8.45.
6-Amino-5-benzoyl-4-phenyl-4H-[1,2]-oxazine-3-carbonitrile
(8). To a mixture of 3.5 g (0.01 mole) of 2a and 0.7 g (0.01
mole) of hydroxylamine hydrochloride in 30 ml of ethanol was
added a solution of potassium carbonate (2.76 g; 0.02 mole in
the minimum amount of water). The reaction mixture was
refluxed for 2 hours then left to cool to room temperature,
diluted with ice-cold water and neutralized with HC1. The
yellow precipitate that formed was collected by filtration and
recrystallized from ethanol to give (2.2 g, 72%) of 8, mp 155-
156 °C (EtOH); ir: ꢀmax (KBr) 3445-3260 (NH2), 2219 (CN),
2-Amino-3-benzoyl-5-cyano-4-phenylpyrrole-1-carbox-
amide (19a). Yellow crystalline solid, mp 195-197 °C
(EtOH/DMF) (2.4 g, ~73%); ir: ꢀmax (KBr) 3425-3215 (NH2),
1
2215 (CN), 1660 & 1687 (2C=O) cm-1, (m/e=330); H nmr (300
MHz, DMSO-d6): ꢁH 5.2 (s, 2H, NH2 exch.), 7.25-7.85 (m, 10H,
Ar. H), 8.32 (s, 2H, NH2, exch.).
Anal. Calcd for (C19H14N4O2): C, 69.08; H, 4.27; N, 16.96.
Found: C, 69.20; H, 4.50; N, 17.10.
2-Amino 3-benzoyl-5-cyano-4-phenylpyrrole-1-thiocarbox-
amide (19b). Reddish brown crystalline solid, mp 172-173 °C
(EtOH/DMF) (2.5 g, 72%); ir: ꢀmax (KBr) 3395-3225 (NH2),
2217 (CN), 1684 (CO) cm-1, (m/e=346); 1H nmr (300 MHz,
DMSO-d6): ꢁH 5.25 (s, 2H, NH2), 7.20-7.80 (m, 10H, Ar. H),
8.35 (s, 2H, NH2, exch.).
1
1682 (C=O) cm-1, (m/e=303); H nmr(300 MHz, DMSO-d6): ꢁH
4.1 (s, 1H, 4-H), 7.1-7.8 (m, 10H, Ar. H), 8.1 (s, 2H, NH2 exch.).
Anal. Calcd for (C18H13N3O2): C, 71.28; H, 4.32; N, 13.85.
Found: C, 71.50; H, 4.50; N, 14.10.
The Reaction of 2a with Hydrazine Hydrate and Phenyl
Hydrazine (General Procedure). To a solution of 3.5 g (0.01
mole) of 2a in 25 ml of ethanol was added an excess of hydrazine
hydrate (~2 ml) or 1.08 g (0.01 mole) of phenyl hydrazine, and the
reaction mixture was refluxed for 2 hours in each case, after which
it was left to cool to room temperature. The formed solid
precipitates were collected by filtration and recrystallized from
EtOH/DMF (1:1) to afford 10a and 10b respectively:
Anal. Calcd for (C19H14N4OS): C, 65.88; H, 4.07; N, 16.17; S,
9.26. Found: C, 65.50; H, 4.10; N, 16.30; S, 9.40.
2-Amino-3-benzoyl-5-cyano-4-phenylpyrrole-1-carbox-
amidine (19c). Yellowish brown crystalline solid, mp 257-259
°C (EtOH/DMF) (2.4 g, 73%); ir: ꢀmax (KBr) 3385-3165 (NH2 &
NH), 2215 (CN), 1680 (CO) cm-1, (m/e=329); 1H nmr (300
MHz, DMSO-d6): ꢁH 4.95 (s, 2H, NH2), 7.1-7.8 (m, 10H, Ar. H),
8.28 (s, 2H, NH2), 8.72 (s, 1H, NH).
6-Amino-5-benzoyl-4-phenyl-1,4-dihydropyridazine-
3-carbonitrile (10a). Dark yellow crystalline solid, mp 207-209
°C (EtOH/DMF) (2 g, 73%); ir: ꢀmax (KBr) 3455- 3255 (NH &
1
NH2), 2220 (CN), 1683 (C=O) cm-1, (m/e=302); H nmr (300
Anal. Calcd for (C19H15N5O): C, 69.29; H, 4.59; N, 21.26.
Found: C, 69.00; H, 4.80; N, 21.60.
MHz, DMSO-d6): ꢁH 3.95 (s, 1H, 4-H), 4.65 (s, 2H, NH2, D2O
exch.), 7.05-7.80 (m, 10H, Ar. H), 8.3 (br. s, 1H, NH, exch.).
Anal. Calcd for (C18H14N4O): C, 71.51; H, 4.67; N, 18.53.
Found: C, 71.70; H, 4.80; N, 18.20.
ACKNOWLEDGEMENT
F. M. Abdelrazek thanks the Alexander von Humboldt-
Foundation (Germany) for granting a research fellowship (Jul.-
Sept. 2006), and Professor P. Metz, Institut für Organische
Chemie, TU Dresden, for his kind hospitality.
6-Amino-5-benzoyl-1,4-diphenyl-1,4-dihydro pyridazine-3-
carbonitrile (10b). Brownish yellow crystalline solid, mp 239-
241 °C (EtOH/DMF) (2.4 g, 63%); ir: ꢀmax (KBr) 3390-3220
1
(NH2), 2215 (CN), 1683 (C=O) cm-1, (m/e=378); H nmr (300
MHz, DMSO-d6): ꢁH 4.05 (s, 1H, 4-H), 6.50-7.80 (m, 15H, Ar.
H), 7.85 (br. s, 2H, NH2, exch.).
REFERENCES
Anal. Calcd for (C24H18N4O): C, 76.17; H, 4.79; N, 14.81.
Found: C, 76.30; H, 4.50; N, 14.60.
[1] F. M. Abdelrazek, N. H. Metwally, Afinidad, 61(510), 134-
138 (2004).
The Reaction of 2a with Cyanoacetamide, Cyanoaceto-
hydrazide and Urea Derivatives (General Procedure). To a