Month 2014
1,4-Phenylene-bis-heterocyclic Derivatives and Pyran Derivatives
neutral. The precipitated solids were filtered off and
recrystallized from ethanol/DMF (5:1) to afford the bis-
pyrazoles 9a–c.
and ammonium acetate (1.16 g; 0.15 mol) in ethanol
(25 ml), and the reaction mixture was stirred overnight at
RT then poured on cold water. The solid precipitates that
appeared were filtered off and recrystallized from ethanol
to afford 11a,b, respectively.
5
-Amino-3-({4-[5-amino-4-cyano-1-phenylpyrazol-3-ylcarbonyl]-
phenyl} carbonyl)-1-phenylpyrazole-4-carbonitrile 9a. Brown
crystals, yield 3.93 g (79%), mp 145°C. υ = 3025 (NH ),
max
2
The identity of the products was inferred from their
À1
+
2
226 (CN), and 1667 (C = O) cm ; m/z = 498 [M ].
δH = 6.79–8.22 (m, 14H, arom. H) and 8.24 (br s, 4H,
NH ). Anal. Calcd for C H N O (498.50): C, 67.46;
melting points and TLC analysis.
Ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-pyran-3-carboxylate
2
11a. Yellow crystalline solid, yield 2.26 g (78%), mp 195°C.
2
28 18 8 2
H, 3.64; N, 22.48. Found: C, 67.50; H, 3.60; N, 22.55.
IR: υ = 3328, 3286 (NH ), 2218 (CN), and 1712 (CO)
max
À1
2
5
-Amino-3-({4-[5-amino-4-cyano-1-p-tolylpyrazol-3-ylcarbonyl]-
+
cm . MS: m/z=284 [M ]; δ =1.076–1.124 (t, J=7.2Hz,
H
phenyl} carbonyl)-1-p-tolylpyrazole-4-carbonitrile 9b.
Dark
3
H, ester CH ), 2.38 (s, 3H, CH ), 4.010–4.082 (q,
3 3
brown crystals, yield 3.5 g (67%), mp 115°C. υ = 3023
max
J=7.2Hz, 2H, CH ), 4.36 (s, 1H, pyran 4H), 6.95 (s, 2H,
2
À1
(
[
NH ), 2224 (CN), and 1663 (C = O) cm ; m/z = 526
M ]. δ = 2.65 (s, 6H, 2CH ), 6.94 (s, 4H, 2NH ), and
2
NH ), and 7.10–7.40 (m, 5H, arom. H). δ = 13.64, 18.04,
2
C
+
H
3
2
3
1
8.68, 57.27, 60.06, 107.22, 119.60, 126.73, 127.11, 128.35,
44.80, 156.48, 158.43, and 165.37. Anal. Calcd for
C H N O (284.31): C, 67.59; H, 5.67; N, 9.85. Found:
7
.00–8.20 (m, 12H, arom. H). Anal. Calcd for C H N O
30 22 8 2
(526.55): C, 68.43; H, 4.21; N, 21.28. Found: C, 68.55; H,
16 16 2 3
4
.30; N, 21.20.
C, 67.50; H, 5.72; N, 9.80.
5-Amino-3-({4-[5-amino-4-cyano-1-p-anisylpyrazol-3-ylcarbonyl]-
Ethyl 6-amino-5-cyano-2,4-diphenyl-4H-pyran-3-carboxylate
1b.
phenyl} carbonyl)-1-p-anisylpyrazole-4-carbonitrile 9c.
Dark
1
Yellow crystalline solid, yield 2.26 g (78%), mp
brown crystals, yield 4.00 g (72%), mp 110°C. υ = 3028
188°C. IR: υ = 3325, 3272 (NH ), 2221 (CN), and 1713
max
max
2
À1
+
À1
+
(
NH ), 2230 (CN), and 1669 (C = O) cm ; m/z=558 [M ].
(CO) cm . MS: m/z= 346 [M ]; δ = 0.783–0.830 (t,
H
J=6.9Hz, 3H, ester CH
2
δ =3.32 (s, 6H, 2CH ), 6.90–8.20 (m, 12H, arom. H), and
), 3.798–3.867 (q, J=6.9Hz, 2H,
3
H
3
CH ), 4.52 (s, 1H, pyran 4H), 7.05 (s, 2H, NH ), and 7.30–
8
.23 (s, 4H, 2NH ). Anal. Calcd for C H N O (558.55): C,
2
2
2
30 22 8 4
7
1
1
.56 (m, 10H, arom. H). δ = 13.13, 38.68, 57.04, 60.08,
08.97, 119.55, 126.99, 127.27, 127.97, 128.38, 128.53,
29.79, 133.05, 144.01, 154.06, 159.09, and 165.42. Anal.
C
64.51; H, 3.97; N, 20.06. Found: C, 64.51; H, 3.97; N, 20.06.
Reaction of the β-keto esters 10a,b with benzaldehyde and
malononitrile to give 11a,b.
A mixture of ethyl
acetoacetate 10a (1.3 g; 0.01 mol) or ethyl benzoyl acetate
0b (1.92 g; 0.01 mol), benzaldehyde (1.06 g; 0.01 mol),
malononitrile (0.66 g; 0.01 mol), and ammonium acetate
1.16 g; 0.15 mol) in ethanol (25 ml) was stirred overnight
Calcd for C H N O (346.38): C, 72.82; H, 5.24; N, 8.09.
21 18 2 3
Found: C, 72.55; H, 5.30; N, 8.15.
1
Reaction of 11a,b with hydrazine hydrate. To a mixture
of 2.84 g (0.01 mol) of 11a or 3.46 g (0.01 mol) of 11b and
(
1
ml (0.01 mol) of hydrazine hydrate (70%) in ethanol
at RT; where a homogeneous solution was obtained.
Then the reaction mixture was poured on cold water. The
solid precipitates that appeared were filtered off and
recrystallized from ethanol to afford the pure products
(25 ml) is added 2–3 drops of TEA. The reaction mixture
was refluxed for 3 h (TLC control) then left to cool at
RT. The contents of the flask in each case were poured
on ice cold water. The precipitate solids were collected
by filtration and recrystallized by ethanol to give pure
1
1a,b, respectively.
Alternative synthesis of 11a,b.
1
5a,b, respectively.
Ethyl 3-amino-6-methyl-4-phenyl-1,4-dihydropyrano[2,3-c]
(
a) Reaction of the β-keto esters 10a,b with
benzylidene malononitrile: A mixture of ethyl
acetoacetate 10a (1.3 g; 0.01 mol) or ethyl benzoyl
acetate 10b (1.92 g; 0.01 mol), benzylidene
malononitrile (1.54 g; 0.01 mol), and ammonium
acetate (1.16 g; 0.15 mol) in ethanol (25 ml) was
stirred overnight at RT where a homogeneous
solution was obtained. Then the reaction mixture
was poured on cold water. The solid precipitates
that appeared were filtered off and recrystallized
from ethanol to afford 11a,b, respectively.
pyrazole-5-carboxylate 15a. Light brown crystalline solid,
yield 2.26 g (78%), mp 190–194°C. IR: υmax = 3335,
À1
3278 and 2285 (NH and NH), and 1710 (CO) cm
.
2
+
MS: m/z = 299 [M ]; δ = 0.596–0.664 (t, J = 10.2 Hz, 3H,
ester CH3), 2.39 (s, 3H, CH3), 3.653–3.753 (q,
H
J = 10.2 Hz, 2H, CH ), 4.88 (s, 1H, pyran 4H), 5.34 (s,
2
2
H, NH ), 7.23–7.72 (m, 5H, arom. H), and 12.14 (s, 1H,
2
NH). Anal. Calcd for C H N O (299.32): C, 64.20; H,
16 17 3 3
5
.72; N, 14.04. Found: C, 64.27; H, 5.65; N, 14.25.
Ethyl 3-amino-4,6-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-
5
-carboxylate 15b.
Light brown crystalline solid, yield
2.26 g (78%), mp 189°C. IR: υmax = 3337, 3285 and 2295
À1
+
(
NH and NH), and 1711 (CO) cm . MS: m/z = 361 [M ];
(
b) Condensation of the β-keto esters 10a,b with benzalde-
hyde followed by malononitrile: To a mixture of ethyl
acetoacetate 10a (1.3 g; 0.01 mol) or ethyl benzoyl acetate
2
δ
= 0.709–0.756 (t, J = 6.9 Hz, 3H, ester CH
3.793 (q, J = 6.9 Hz, 2H, CH ), 4.44 (s, 1H, pyran 4H), 4.97
(s, 2H, NH ), 6.89–7.95 (m, 10H, arom. H), and 12.86 (s,
1H, NH). Anal. Calcd for C21 (361.93): C, 69.79;
H, 5.30; N, 11.63. Found: C, 69.75; H, 5.38; N, 11.50.
), 3.722–
H
3
2
1
0b (1.92 g; 0.01 mol) and benzaldehyde (1.06 g;
2
0
.01 mol) in ethanol (25 ml) was added TEA (0.5 ml), and
H N O
19 3 3
the reaction mixture was refluxed for 2 h and then left to cool
at RT overnight. The solid precipitates were filtered off and
washed with ethanol. Without further purification, these
products were taken with malononitrile (0.66 g; 0.01 mol)
Reaction of 11a,b with urea and thiourea.
To a
mixture of 2.84 g (0.01 mol) of 11a or 3.46 g (0.01 mol)
of 11b and (0.6 g; 0.01 mol) of urea or 0.76 g
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet