Synthetic studies on the synthesis of some new fused heterocyclic compounds derived from 3,5-pyrazolidinedione

Article abstract of DOI:10.1002/jccs.200700016

Condensation of 1-phenylpyrazolidine-3,5-dione 1 with 3-formylchromone afforded 4-(chromenylmethylene) pyrazolidinedione 2, which was reacted with hydrazine or hydroxylamine in different molar ratios and conditions to give the corresponding pyrazole and isoxazole derivatives 3-8, respectively. Compound 2 was subject to react with ammonia, N,S- or S,S-acetals, mercaptoacetic acid, cyanoacetamide or cyanothioacetamide to give the corresponding pyridine, dithiine, thiazine and thiophene, 9-14, respectively. The reaction of compound 2 with thiourea, guanidine, cystamine, o-aminothiophenol, ethylenediamine, o-phenelenediamine or barbituric acid afforded the corresponding thiazine, pyrimidine, thiazepine, diazepine, and pyran derivatives 17-23, respectively. The study of the reaction of compound 2 with nucleophiles via chromene ring opening was investigated.

Full text of DOI:10.1002/jccs.200700016

Journal of the Chinese Chemical Society, 2007, 54, 93-102
93
Synthetic Studies on the Synthesis of Some New Fused Heterocyclic
Compounds Derived from 3,5-Pyrazolidinedione
A. Khodairy
Chemistry Department, Faculty of Science, South Valley University, 82524 Sohag, Egypt
Condensation of 1-phenylpyrazolidine-3,5-dione 1 with 3-formylchromone afforded 4-(chromenyl-
methylene)pyrazolidinedione 2, which was reacted with hydrazine or hydroxylamine in different molar
ratios and conditions to give the corresponding pyrazole and isoxazole derivatives 3-8, respectively. Com-
pound 2 was subject to react with ammonia, N,S- or S,S-acetals, mercaptoacetic acid, cyanoacetamide or
cyanothioacetamide to give the corresponding pyridine, dithiine, thiazine and thiophene, 9-14, respec-
tively. The reaction of compound 2 with thiourea, guanidine, cystamine, o-aminothiophenol, ethylenedi-
amine, o-phenelenediamine or barbituric acid afforded the corresponding thiazine, pyrimidine, thiaze-
pine, diazepine, and pyran derivatives 17-23, respectively. The study of the reaction of compound 2 with
nucleophiles via chromene ring opening was investigated.
Keywords: Chromone; Pyrazolidine-3,5-dione; Pyridine; Thiazepine; Diazepine; Michael reac-
tion.
INTRODUCTION
3-Formylchromone has been used as precursor to pre-
ized as 4-[(4-oxo-4H-chromen-3-yl)methylene]-1-phenyl-
pyrazolidine-3,5-dione (2) in good yield. Its IR spectrum
showed the following absorption bands at n: 3321 due to
N-H and 1666, 1680, 1702 cm-1 due C=O groups. 1H NMR
spectrum showing signals at d: 8.6 (s, 1H, 2-CH), 8.0-7.0
(m, 10H, Harom + N-H) and 6.8 (s, 1H, Hmethylene) (Scheme I).
The reaction of the compound 2 with hydrazine hy-
pare a diversity of heterocyclic systems,1,2 owing to the
presence of an a,b-unsaturated keto-function, a conjugated
second carbonyl group at C3 and in particular due to the ac-
tive center at position-2. This center is very reactive to-
wards Michael addition of nucleophiles3-5 with opening of
the g-pyrone ring6,7 and followed by a new cyclization.
Moreover, the well-known biological activity of pyra-
zoles1,8-10 directed our attention to use the starting com-
pound 4-[(chromen-3-yl)methylene]pyrazolidine-3,5-di-
one 2 to obtain novel isoxazole, pyridine, dithiine, thiazine,
thiazepine and diazepine nuclei fused with a pyrazole ring
system. The present work is a continuation of our previous
reports8-10 that deal with synthesis of new pyrazole deriva-
tives condensed with five and six-membered heterocycles
attached that have promising biological activity.
drate in a molar ratio 1:1 in dioxane/TEA afforded a prod-
uct of g-pyrone ring opening and pyrazole ring closure,
namely; 4-{[5-(2-hydroxyphenyl)-1H-pyrazol-4-yl]meth-
ylene}-1-phenylpyrazolidine-3,5-dione (3), in good yield.
Compound 3 gave a deep violet colour with FeCl3 confirm-
ing the presence of phenolic (OH) obtained by g-pyrone
ring opening, and its 1H NMR spectrum showed the disap-
pearance of the signal at d 8.6 ppm due to the C2 proton.1
When compound 2 was reacted with hydrazine in 1:2 molar
ratio in DMF, it gave 4-[5-(2-Hydroxyphenyl)-1H-pyr-
azol-4-yl]-1-phenyl-1,5,6,6a-tetrahydropyrazolo[3,4-c]-
pyrazol-3(2H)-one (4) in low yield. It was found that the
pyrone ring and pyrazoline exocyclic enone system are
used in the reaction with excess hydrazine, while the pyr-
one ring is used in the reaction with an equimolare of hyra-
zine [1], while the reaction of compound 2 with hydrazine
in a 1:1 molar ratio in acetic acid gave 5-acetyl-4-(4-oxo-
4H-chromen-3-yl)-1-phenyl-1,4,5,6-tetrahydropyrazolo-
RESULTS AND DISCUSSION
Condensation of 3-formylchromone with 1-phenyl-
pyrazolidine-3,5-dione (1), in glacial acetic acid and so-
dium acetate,1 gave a red precipitate, which was character-
* Corresponding author. E-mail: khodairy@yahoo.com

94 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Khodairy
Scheme I
O
O
O
O
N
O
O
CHO
HN
HN
AcONa
AcOH
+
N
O
O
1
2
[3,4-c]pyrazol-3(2H)-one (5) as an exocyclic enone ring
system involved (Scheme II).
group to C2 pyrone ring and opening, followed by cyclo-
condensation of the CH2 group with the benzoyl carbonyl
group (Scheme III).
Similarly, treatment of compound 2 with hydoxyl-
amine in a 1:1 or 1:2 molar ratio, gave 4-{[5-(2-hydroxy-
phenyl)isoxazol-4-yl]methylene}-1-phenylpyrazolidine-
3,5-dione (6), 3-(4-oxo-4H-chromen-3-yl)-6-phenyl-1,3,5,6-
tetrahydro-4H-pyrazolo[3,4-c]isoxazol-4-one (7) and 3-[5-
(2-hydroxyphenyl)isoxazol-4-yl]-6-phenyl-1,3,5,6-tetra-
hydro-4H-pyrazolo[3,4-c]isoxazol-4-one (8), respectively
(Scheme II).
Treatment of compound 2 with cyanoacetamide or
cyanothioacetamide in the presence of sodium ethoxide af-
forded the corresponding 5-[(3,5-dioxo-1-phenylpyrazoli-
din-4-ylidene)methyl]-6-(2-hydroxy-phenyl)-2-oxo-1,2-
dihydropyridine-3-carbonitrile (13) and 5-[(3,5-dioxo-1-
phenylpyrazolidin-4-ylidene)methyl]-6-(2-hydroxyphen-
yl)-2-thioxo-1,2-dihydropyridine-3-carbonitrile (14), re-
spectively. IR spectra showed new absorption bands corre-
sponding to OH at n 3400, NH at n 3211, CºN at n 2213,
C=O at n 1689 and C=S at n 1422 cm-1, respectively. The
reaction mechanism proceeded via pyrone ring opening
and cyclocondensation of the NH2 group with the benzoyl
carbonyl group (Scheme IV).
Compound 2 was subject to react with ammonia in
boiling DMF; 3-pyrazolo(3,4-b)pyridin-3-one derivative 9
was obtained. IR spectrum showed absorption bands corre-
sponding to OH and C=Oketone at n 3400 and 1666 cm-1, re-
spectively (Scheme III).
The addition of S,S- and N,S-acetals to compound 2
using phase transfer catalysis (PTC) conditions [K2CO3,
Dioxane, TBAB] was carried out. Thus, compound 2 re-
acted with a mixture of ethyl cyanoacetate and carbon
disulfide or malononitrile and phenylisothiocyanate, where
ethyl cyano[4-(3,5-dioxo-1-phenylpyrazolidin-4-yl)-5-(2-
hydroxybenzoyl)-4H-[1,3]dithiin-2-ylidene]acetate (10)
and 2-[4-(3,5-dioxo-1-phenylpyrazolidin-4-yl)-5-(2-hy-
droxybenzoyl)-3-phenyl-3,4-dihydro-[1,3]thiazin-2-yli-
dene]malononitrile (11) were obtained. IR spectra showed
new absorption bands corresponding to CºN at 2210 cm-1
and C=Oester at 1734 cm-1, respectively. The reaction path-
way proceeded via a nucleophilic attack of the SH group to
C2 pyrone with ring opening followed by a nucleophilic ad-
dition of the SH group or the NH group to exodouble bond
(Scheme III).
Compound 14 was allowed to react with hydrazine or
hydroxylamine in acetic acid to give 5-(2-acetyl-4-oxo-6-
phenyl-1,2,3,4,5,6-hexahydropyrazolo[3,4-c]-pyrazol-3-
yl)-6-(2-hydroxyphenyl)-2-thioxo-1,2-dihydropyridine-3-
carbonitrile (15) and 6-(2-hydroxyphenyl)-5-(4-oxo-6-
phenyl-3,4,5,6-tetrahydro-1H-pyrazolo[3,4-c]isoxazol-3-
yl)-2-thioxo-1,2-dihydro-pyridine-3-carbonitrile (16), re-
spectively. Herein we obtained the same products 15 and 16
by an alternate route, via treatment of compound 2-ace-
tylpyrazolo[3,4-c]pyrazole derivative 5 or 3-(4-oxo-4H-3-
chromenyl)-6-phenyl-1H-pyrazolo[3,4-c]isoxazol-4-one 7
with cyanothioacetamide in the presence of sodium eth-
oxide. The structure of compounds 15 and 16 was estab-
lished on the basis of their correct elemental analysis and
spectral data (Scheme IV).
Also, mercaptoacetic acid reacted with compound 2
using phase transfer catalysis conditions (PTC) to yield
4-[(3,5-dioxo-1-phenylpyrazolidin-4-ylidene)methyl]-3-
(2-hydroxyphenyl)thiophene-2-carboxylic (12). The reac-
tion pathway proceeded via nucleophilic attack of the SH
4-{[4-(2-Hydroxyphenyl)-2-imino-2H-1,3-thiazin-
5-yl]methylene}-1-phenylpyrazolidine-3,5-dione (17) and
4-{1-[2-amino-4-(2-hydroxyphenyl)pyrimidin-5-yl]meth-
ylene}-1-phenylpyrazolidine-3,5-dione (18) were obtained
via the reaction of compound 2 with thiourea or guanidine

Heterocyclic Componuds Made from 3,5-Pyrazolidinedione
J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 95
Scheme II
OH
NH
O
NH2NH2/
1:1
N
O
H N
Dioxane/TEA
N
3
Ph
N
NH
OH
O
N H
N H
NH NH /
1:2
2
2
H N
N
DMF
Ph
4
O
O
N
O
O
NH2NH2/
1:1
O
NCOCH3
N H
O
G. AcOH
H N
H N
O
N
5
Ph
Ph
2
OH
O
O
1:1
NH2OH HCl /
N
H N
O
Dioxane + DMF
N
Ph
6
O
O
NH OH HCl /
1:1
2
G. AcOH
O
O
N H
H N
N
7
Ph
N
O
OH
O
O
NH2OH HCl / 1:2
DMF
N H
H N
N
8
Ph

96 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Khodairy
Scheme III
in the presence of sodium ethoxide (Scheme V).
afford 6-[(3,5-dioxo-1-phenylpyrazolidin-4-ylidene)-meth-
yl]-7-(2-hydroxyphenyl)-2H-pyrano[2,3-d]pyrimidine-
2,4(3H)-dione (23) (Scheme V).
Binucleophiles, namely cystamine HCl, o-aminothio-
phenol, ethylenediamine or o-phenylenediamine, were re-
acted with compound 2 in the presence of sodium eth-
oxide7,14 to give the corresponding 4-[1,4-thiazepin-6-yl]-
19, 4-[1,5-benzothiazepin-3-yl]- 20, 4-[1,4-diazepin-6-yl]-
21 and 4-[1,5-benzodiazepin-3-yl]methylene-1-phenyl-
pyrazolidine-3,5-dione 22, respectively. The reaction mech-
anism proceeded via a nucleophilic attack of the SH group
or the NH2 group to the C2-bond with ring opening, fol-
lowed by cyclocondensation of the NH2 group with the
benzoyl carbonyl group. Finally, compound 2 was treated
with barbituric acid in the presence of sodium ethoxide to
EXPERIMENTAL
Melting points are uncorrected and were determined
on a Koffler melting point apparatus. IR spectra were re-
corded on a Nicolet 710 FT-IR spectrophotometer using
1
the KBr technique. H NMR spectra were recorded on a
Varian EM 360 at (60 MHz), in DMSO-d6 as a solvent, us-
ing tetramethylsilane (TMS) as internal standard. Elemen-

Heterocyclic Componuds Made from 3,5-Pyrazolidinedione
J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 97
Scheme IV
tal analyses were carried out at the microanalytical labora-
tories of the Faculty of Science, Cairo University. The ana-
lytical and physical data are listed in Table 1.
on heat was filtered off, washed with water, and crystal-
lized. IR (KBr), nmax: 3321 (N-H), 1702, 1688, 1669 cm-1
1
(C=O); H NMR (DMSO-d6), d: 8.3 (s, 1H, 2-Hchromene),
8.0-7.1 (m, 10H, Harom + N-Hpyrazolidine), 6.0 (s, 1H, CHmeth-
ylene).
4-[(4-Oxo-4H-chromen-3-yl)methylene]-1-phenylpyr-
azolidine-3,5-dione (2)
A mixture of the compound 1 (1.76 g, 0.01 mol), 3-
formylchromone (1.74 g, 0.01 mol) and anhydrous sodium
acetate (1.68 g, 0.02 mol), in glacial acetic acid (20 mL),
was refluxed for 0.5 h. The precipitate product so formed
4-{[5-(2-Hydroxyphenyl)-1H-pyrazol-4-yl]methylene}-
1-phenyl-pyrazolidine-3,5-dione (3)
A mixture of compound 2 (0.01 mol, 2.32 g), hydra-
zine hydrate (0.01 mol, 0.05 mL) and TEA (0.01 mol, 1.4

98 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Khodairy
(KBr), nmax: 3422 (OH), 3211, 3201 (2NH), 1701, 1677
(CO); 1H NMR (DMSO-d6), d: 11.0 (s, 1H, OH), 9.2 (br,
Scheme V
1H, NH), 8.3 (s, 1H, CHmethylene), 8.0-7.1 (m, 10H, Harom
N-Hpyrazolidine), 6.7 (s, 1H, N=CH).
+
4-[5-(2-Hydroxyphenyl)-1H-pyrazol-4-yl]-1-phenyl-
1,5,6,6a-tetrahydropyrazolo[3,4-c]pyrazol-3(2H)-one
(4)
A mixture of compound 2 (0.003 mol, 0.69 g) and
hydrazine hydrate (0.006 mol, 0.32 mL), in DMF (15 mL),
was refluxed for 4 h. On cooling, the reaction mixture was
poured into ice-cold water containing drops of HCl. The
precipitated solid was filtered, dried, and crystallized
(Scheme II, Table 1). IR (KBr), nmax: 3422 (OH), 3321-
3100 (4NH), 1682 (C=O); 1H NMR (DMSO-d6), d: 11.2 (s,
1H, OH), 9.2 (br, 2H, 2NH), 8.2 (s, 1H, NH), 7.7-7.1 (m,
10H, Harom. + NHpyrazolidine), 6.5 (s, 1H, N=CH), 4.0 (s, 1H,
CH).
5-Acetyl-4-(4-oxo-4H-chromen-3-yl)-1-phenyl-1,4,5,6-
tetrahydropyrazolo[3,4-c]pyrazol-3(2H)-one (5)
A mixture of compound 2 (0.002 mol, 0.46 g) and
hydrazine hydrate (0.002 mol, 0.1 mL) was refluxed in gla-
cial acetic acid (20 mL) for 6 hrs. The reaction mixture was
left to cool; the formed precipitate was filtered, dried,
washed with water and crystallized (Scheme I, Table 1). IR
(KBr) nmax: 3328, 3200 (2 N-H), 1706, 1680, 1665 (C=O);
1H NMR (DMSO-d6), d: 11.0 (s, 1H, NH), 9.0 (s, 1H,
=CHchromene), 7.9-7.2 (m, 10H, Harom + N-Hpyrazolidine), 4.0 (s,
1H, CH), 2.2 (s, 3H, CH3).
4-{[5-(2-Hydroxyphenyl)isoxazol-4-yl]methylene}-1-
phenylpyrazolidine-3,5-dione (6)
A mixture of compound 2 (0.01 mol, 2.32 g) and hy-
droxylamine HCl (0.01 mol, 0.7 g) in mixed solvent di-
oxane (20 mL) and DMF (5 mL) was refluxed for 3 hrs. The
mixture was left to cool and the precipitated product so
formed was filtered and crystallized. IR (KBr), nmax: 3349
(OH), 1701, 1688 (C=O); 1H NMR (DMSO-d6), d: 13.0 (s,
1H, OH), 8.0 (s, 1H, =CH), 7.7-7.1 (m, 10H, Harom
NHpyrazolidine), 6.0 (s, 1H, N=CH).
+
3-(4-Oxo-4H-chromen-3-yl)-6-phenyl-1,3,5,6-tetrahy-
dro-4H-pyrazolo[3,4-c]isoxazol-4-one (7)
mL) was refluxed in dioxane (20 mL) for 2 hrs. On cooling,
the formed precipitate was filtered off and crystallized. IR
A mixture of compound 2 (0.002 mol, 0.46 g) and

Heterocyclic Componuds Made from 3,5-Pyrazolidinedione
Table 1. Analytical data of the new compounds
J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 99
Elemental Analyses
Calculated/Found.
Compd.
No.
M.P. (°C) Yield
Mol. Formula
(Mol.Wt)
Solvent
(%)
98
66
90
29
40
56
60
69
70
93
30
75
44
95
35
58
55
55
55
33
C%
H%
N%
S%
2
240-2
EtOH
170-2
EtOH
140-2
dioxane
211
C19H12N2O4
(332.31)
68.67
68.48
65.89
65.97
63.33
63.10
64.94
64.81
65.70
65.51
65.70
65.90
62.98
62.77
68.88
68.68
62.06
62.31
66.33
66.56
63.76
63.50
61.27
61.46
61.53
61.33
61.53
61.30
64.34
64.11
64.44
64.61
68.32
68.12
67.37
67.50
71.08
71.20
62.45
62.66
3.64
3.87
7.04
7.31
4.47
4.51
4.15
4.28
3.77
3.82
3.77
3.57
3.89
3.66
3.95
3.70
3.47
3.61
3.54
3.40
3.40
3.89
3.86
3.67
3.52
3.70
3.61
3.79
4.05
4.21
3.38
3.10
3.90
3.70
4.83
4.70
4.29
4.40
3.19
3.33
08.43
08.22
16.18
16.35
23.32
23.20
14.43
14.35
12.10
12.26
12.10
12.19
15.46
15.22
12.68
12.79
06.89
06.57
14.06
14.24
13.52
13.39
17.86
17.62
16.31
16.04
14.35
14.20
18.76
18.90
10.73
10.90
09.60
09.47
14.96
14.78
13.26
13.09
12.66
12.40
3
C19H14N4O3
(346.34)
4
C19H16N6O2
(360.37)
5
C21H16N4O4
(388.38)
DMF
185-7
DMF
115-6
EtOH
320
6
C19H13N3O4
(347.33)
7
C19H13N3O4
(347.33)
8
C19H14N4O4
(362.34)
EtOH
299
9
C19H13N3O3
(331.33)
CH3CN
216
12
13
14
15
16
17
18
19
20
21
22
23
C21H14N2O5S
(406.41)
7.89
7.60
Dioxane
261
C22H14N4O4
(398.38)
DMF
188
C22H14N4OS
(414.44)
7.74
7.88
6.81
6.97
7.47
7.65
8.21
8.02
EtOH
197-9
DMF
210-2
EtOH
109-111
MeCN
154
C24H18N6O3S
(470.50)
C22H15N5O3S
(429.45)
C20H14N4O3S
(390.41)
C20H15N5O3
(373.37)
DMF
243-5
EtOH
176-9
Dioxane
176-9
EtOH
176-9
DMF
> 300
AcOH
C21H17N3O3S
(391.44)
8.19
8.30
7.29
7.35
C25H17N3O3S
(439.49)
C21H18N4O3
(374.40)
C25H18N4O3
(422.44)
C23H14N4O6
(442.38)
hydrazine hydrate (0.002 mol, 0.1 mL) was refluxed in gla-
cial acetic acid (20 mL) for 6 hrs. The reaction mixture was
left to cool; the formed precipitate was filtered, dried,
washed with water, and crystallized. IR (KBr), nmax: 3320
(NH), 1684, 1665 (C=O); 1H NMR (DMSO-d6), d: 11.0 (s,
NHpyrazolidine), 4.0 (s, 1H, CH).
3-[5-(2-Hydroxyphenyl)isoxazol-4-yl]-6-phenyl-1,3,5,6-
tetrahydro-4H-pyrazolo[3,4-c]isoxazol-4-one (8)
Compound 8 was obtained from treatment of com-
pound 2 (0.02 mol, 0.46 g) and hydroxylamine HCl (0.04
1H, NH), 8.0 (s, 1H, 2Hchromene), 7.9-7.2 (m, 10H, Harom
+

100 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Khodairy
mol, 0.28 g) in DMF (20 mL), using the same procedure as
4-[(3,5-Dioxo-1-phenylpyrazolidin-4-ylidene)methyl]-3-
(2-hydroxyphenyl)thiophene-2-carboxylic (12)
described for compound 4 and crystallized. IR (KBr), nmax
:
1
3400 (OH), 3300, 3210 (2NH), 1690 (CO); H NMR
(DMSO-d6), d: 11.0 (s, 1H, OH), 9.0 (br, 1H, NH), 8.6 (s,
1H, NH), 7.8-7.1 (m, 10H, Harom. + NHpyrazolidine), 3.8 (s, 1H,
CH).
To a mixture of anhydrous potassium carbonate (3 g),
dry dioxane (20 mL), compound 2 (0.01 mol, 2.32 gm) and
a catalytic amount of tetrabutylammonium bromide (TBAB),
was added an equimolar amount 0.01 mol of mercapto-
acetic acid (1 mL). The reaction mixture was vigorously
stirred for 4 hr. at 60 oC until completion of the reaction
(TLC). The reaction mixture was filtered and the filtrate
was evaporated in vacuo. The residual solid was filtered,
washed with water, and crystallized. IR (KBr), nmax: 3400-
2500 (OH, NH), 1706-1678 (C=O); 1H NMR (DMSO-d6),
d: 14.0 (s, 1H, COOH), 10.5 (s, 1H, OH), 7.8-7.0 (m, 7H,
Harom + NH), 6.0 (s, 1H, =CH).
5-(2-Hydroxybenzoyl)-1-phenyl-1,2-dihydro-3H-pyr-
azolo[3,4-b]pyridin-3-one (9)
A mixture of compound 2 (0.002 mol, 0.46 g) and am-
monium acetate (0.002 mol, 0.16 g) was refluxed in di-
methyformamide (10 mL) for 6 hrs. The reaction mixture
was poured into ice-cold water (100 mL) containing HCl (5
mL); the formed precipitate was filtered, dried, and crystal-
lized. IR (KBr), nmax: 3322 (OH), 3210 (NH), 1698, 1690
(C=O); 1H NMR (DMSO-d6), d: 13.0 (s, 1H, OH), 8.6 (s,
1H, 2-Hpyridine), 7.9-7.0 (m, 10H, Harom + NHpyrazoline).
5-[(3,5-Dioxo-1-phenylpyrazolidin-4-ylidene)methyl]-6-
(2-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbo-
nitrile (13) and 5-[(3,5-Dioxo-1-phenylpyrazolidin-4-
ylidene)methyl]-6-(2-hydroxyphenyl)-2-thioxo-1,2-di-
hydropyridine-3-carbonitrile (14)
Ethyl cyano-[4-(3,5-dioxo-1-phenylpyrazolidin-4-yl)-5-
(2-hydroxybenzoyl)-4H-[1,3]dithiin-2-ylidene]acetate
(10) and 2-[4-(3,5-Dioxo-1-phenylpyrazolidin-4-yl)-5-
(2-hydroxybenzoyl)-3-phenyl-3,4-dihydro[1,3]thiazin-2-
ylidene]malononitrile (11)
General procedure
A mixture of compound 2 (0.01 mol, 2.32 g), cyano-
acetamide (0.01 mol, 0.86 g) or cyanothioacetamide (0.01
mol, 1 g) and sodium ethoxide (0.26 g of Na in 40 mL etha-
nol) was refluxed for 6 hrs. On cooling, the mixture was
poured into ice-cold water (100 mL) containing HCl (3
mL). The resulting product was filtered and crystallized.
Compound 13. IR (KBr), nmax: 3467 (OH), 3300,
General procedure
A mixture of anhydrous potassium carbonate (3 g),
dry dioxane (30 mL), TBAB (0.003 g), carbon disulfide (3
mmol, 0.22 mL), ethyl cyanoacetate (3 mmol, 0.34 mL) or
malononitrile (0.2 g) and phenyl isothiocyanate (0.38 mL)
was stirred for 2 hr. at room temperature and stirred for 2 hr.
at 60 °C. To the reaction mixture was added compound 2
(0.003 mol, 0.69 g). The reaction mixture was stirred for 3
hr. at 80 °C until the completion of the reaction (TLC). The
reaction mixture was filtered and the filtrate was evapo-
rated under vacuum. The solid residue so formed was
washed with water and crystallized.
1
3211 (2NH), 2213 (CºN), 1700-1678 (C=O); H NMR
(DMSO-d6), d: 12.3 (s, 1H, OH), 9.2 (s, 1H, NH), 8.7 (s,
1H, 4-Hpyridine), 7.9-7.3 (m, 10H, Harom + NH), 6.1 (s, 1H,
=CH).
Compound 14. IR (KBr), nmax: 3467 (OH), 3300,
3211 (2NH), 2213 (CºN), 1700-1678 (C=O), 1052 (C=S);
1H NMR (DMSO-d6), d: 12.3 (s, 1H, OH), 9.0 (s, 1H, NH),
8.7 (s, 1H, 4-Hpyridine), 7.8-7.1 (m, 10H, Harom + NH), 6.8 (s,
1H, =CH).
Compound 10. IR (KBr), nmax: 3400 (OH), 3221
(NH), 2219 (CºN), 1734 (C=Oester), 1702-1660 (C=O); 1H
NMR (DMSO-d6), d: 11.0 (s, 1H, OH), 7.7-7.0 (m, 10H,
Harom + NHpyrazolidine), 6.3 (s, 1H, 6-Hdithiine), 4.3-4.0 (q, 2H,
OCH2CH3), 3.8 (d, 1H, 4-Hdithiine), 3.3 (d, 1H, 4-Hpyrazole),
1.2-0.9 (t, 3H, OCH2CH3).
5-(2-Acetyl-4-oxo-6-phenyl-1,2,3,4,5,6-hexahydropyr-
azolo[3,4-c]pyrazol-3-yl)-6-(2-hydroxyphenyl)-2-thi-
oxo-1,2-dihydropyridine-3-carbonitrile (15) and 6-(2-
hydroxyphenyl)-5-(4-oxo-6-phenyl-3,4,5,6-tetrahydro-
1H-pyrazolo[3,4-c]isoxazol-3-yl)-2-thioxo-1,2-dihydro-
pyridine-3-carbonitrile (16)
Compound 11. IR (KBr), nmax: 3400-2500 (OH,
NH), 2210 (CºN), 1697, 1678 (2C=O); 1H NMR (DMSO-
d6), d: 14.0 (s, 1H, OH), 7.9-7.0 (m, 15H, Harom + NH), 6.0
(s, 1H, 6-Hthiazine), 4.0 (d, 1H, 4-Hthiazine), 3.4 (d, 1H,
4-Hpyrazole).
General procedure A
A mixture of compound 5 (0.01 mol, 3.88 g) or com-

Heterocyclic Componuds Made from 3,5-Pyrazolidinedione
J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 101
pound 7 (0.01 mol, 3.47 g), cyanothioacetamide (0.01 mol,
1 g) and sodium ethoxide (0.26 g of sodium metal in 40 mL
ethanol) was refluxed for 6 hrs. On cooling, the mixture
was poured into ice-cold water (100 mL) containing HCl (4
mL). The resulting product was filtered and crystallized
from the appropriate solvent.
ter and crystallized from the appropriate solvent to give
compounds 17-23, respectively.
Compound 17. IR (KBr), nmax: 3350 (OH), 3230,
3190 (2NH), 1701, 1695 (2CO); 1H NMR (DMSO-d6), d:
14.1 (s, 1H, OH), 9.0 (s, 1H, NH), 7.7-7.0 (m, 11H, Harom.
NH), 6.8 (s, 1H, =CH).
+
General procedure B
Compound 18. IR (KBr), nmax: 3350 (OH), 3300,
1
3230, 3120 (NH + NH2), 1700, 1685 (2CO); H NMR
A solution of compound 14 (0.01 mol, 4.14 g) and
hydrazine hydrate (0.01 mol, 0.5 mL) or hydroxyl amine
(0.01 mol, 0.69 g) in glacial acetic acid (40 mL) was
refluxed for 3 hrs. The reaction solution was left overnight
to give compounds 15 and 16.
(DMSO-d6), d: 14.0 (s, 1H, OH), 7.7-7.0 (m, 11H, Harom.
+
NH), 6.7 (s, 1H, =CH), 5.0 (br, 2H, NH2).
Compound 19. IR (KBr), nmax: 3350 (OH), 3230
(NH), 1702, 1685 (2CO). 1H NMR (DMSO-d6), d: 12.6 (s,
1H, OH), 7.7-7.0 (m, 11H, Harom. + NH + CHthiazepine), 6.7 (s,
1H, =CH), 3.2-2.4 (m, 4H, 2CH2).
Compound 15. IR (KBr), nmax: 3467 (OH), 3310,
3221, 3122 (N-H), 2203 (CºN), 1700, 1678 (C=O), 1052
(C=S); 1H NMR (DMSO-d6), d: 9.5 (s, 2H, 2NH), 8.7 (s,
1H, C-4-Hpyridine), 7.8-7.0 (m, 10H, Harom. + NH), 4.0 (s, 1H,
CH), 2.4 (s, 3H, CH3).
Compound 20. IR (KBr), nmax: 3380 (OH), 3200
(NH), 1700, 1680 (2CO). 1H NMR (DMSO-d6), d: 14.0 (s,
1H, OH), 7.9-7.3 (m, 15H, Harom. + NH + CHbenzothiazepine),
6.8 (s, 1H, =CH).
Compound 16. IR (KBr), nmax: 3467 (OH), 3310,
3221, 3122 (3NH), 2203 (CN), 1678 (CO), 1052 (C=S); 1H
NMR (DMSO-d6), d: 9.5 (s, 2H, 2NH), 8.8 (s, 1H, C-4-
Hpyridine), 7.8-7.0 (m, 10H, Harom. + NH), 4.2 (s, 1H, CH).
Compound 21. IR (KBr), nmax: 3370 (OH), 3250,
3100 (2NH), 1703, 1695 (2CO); 1H NMR (DMSO-d6), d:
10.9 (s, 1H, OH), 9.0 (s, 1H, NH), 7.8-7.1 (m, 11H, Harom.
+
NH + CHdiazepine), 6.7 (s, 1H, =CH), 3.0-2.2 (m, 4H, 2CH2).
Compound 22. IR (KBr), nmax: 3350 (OH), 3210
(NH), 1700, 1689 (2CO); 1H NMR (DMSO-d6), d: 14.0 (s,
1H, OH), 7.9-7.3 (m, 15H, Harom. + NH + CHbenzodiazepine),
6.8 (s, 1H, =CH).
4-{[4-(2-Hydroxyphenyl)-2-imino-2H-1,3-thiazin-5-yl]-
methylene}-1-phenylpyrazolidine-3,5-dione (17), 4-{1-
[2-amino-4-(2-hydroxyphenyl)pyrimidin-5-yl]methyl-
ene}-1-phenylpyrazolidine-3,5-dione (18), 4-{[5-(2-hy-
droxyphenyl)-2,3-dihydro-1,4-thiazepin-6-yl]methyl-
ene}-1-phenylpyrazolidine-3,5-dione (19), 4-{[4-(2-hy-
droxyphenyl)-1,5-benzothiazepin-3-yl]methylene}-1-
phenylpyrazolidine-3,5-dione (20), 4-{[5-(2-hydroxy-
phenyl)-2,3-dihydro-1H-1,4-diazepin-6-yl]methylene}-
1-phenylpyrazolidine-3,5-dione (21), 4-{[4-(2-hydroxy-
phenyl)-1H-1,5-benzodiazepin-3-yl]methylene}-1-phen-
ylpyrazolidine-3,5-dione (22), and 6-[(3,5-dioxo-1-phen-
ylpyrazolidin-4-ylidene)methyl]-7-(2-hydroxyphenyl)-
2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione (23)
Compound 23. IR (KBr), nmax: 3340 (OH), 3200,
1
3122 (2NH), 1700, 1692, 1685, 1679 (4C=O); H NMR
(DMSO-d6), d: 14.1 (s, 1H, OH), 9.0 (s, 1H, NH), 8.0 (s,
1H, =CH), 7.9-7.0 (m, 11H, Harom. + NH), 6.8 (s, 1H,
=CHpyran).
Received March 16, 2006.
REFERENCES
General procedure
A mixture of compound 2 (0.01 mol, 2.32 g), the ap-
propriate reagent (0.01 mol), namely thiourea (0.76 g),
guanidine, HCl (0.9 g), ethylenediamine (0.6 mL), o-phen-
ylenediamine (1.08 g), o-aminothiophenol (1.19 mL),
cystamine HCl (1.13 g), barbituric acid (1.28 g) and so-
dium ethoxide (0.26 g of sodium metal in 40 mL ethanol)
was refluxed for 6 hrs. The reaction mixture was poured
into ice-cold water (100 mL) containing HCl (5 mL); the
formed precipitate was filtered off, dried, washed with wa-
1. Abass, M.; Hassan, A. Chem. Papers 2003, 57, 266.
2. Ghosh, C. K.; Ray, A.; Patra, A. J. Heterocycl. Chem. 2001,
38, 1459.
3. Abass, M.; Hassan, A. Chem. Papers 2003, 57, 266.
4. Ghosh, C. K.; Ray, A.; Patra, A. J. Heterocycl. Chem. 2001,
38, 1459.
5. Quiroga, J.; Mejia, Insuasty, B.; Abonia, R.; Ghosh, K. C.;
Ray, A.; Patra, A.; Low, J. N. J. Heterocycl. Chem. 2002, 39,
51.

102 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Khodairy
6. Ellis, G. P. John Wiley and Sons, Inc., New York, 1977; p
972.
Chem. Res. (s), 1998, 178, (m), 1998, 859.
10. Khodairy, A. Phosphorous, Sulfur and Silicon 2000, 160,
159.
7. Ghosh, C. K.; SinhaRoy, D. K.; Mukhopadhyay, K. K. J.
Chem. Soc. Perkin Trans. 1, 1979, 1964.
8. Dean, F. M.; Johnson, R. S. J. Chem. Soc. Perkin Trans. 1,
1981, 224.
11. Khodairy, A.; Ghattas, A.-B. A. G.; Abdel-Rahman, M. A.;
Younes, S. Phosphorous, Sulfur and Silicon 2003, 178, 1781.
12. Abdel-Rahman, M. A.; Ghattas, A.-B. A. G.; Khodairy, A.;
Younes, S. J. Chin. Chem. Soc. 2004, 51, 103.
9. Ghosh, C. K.; Bhattachachrya, S.; Ghoshal, N.; Achari, B. J.