The reaction of 1-phenylpyrazolidine-3,5-dione with active nitriles using phase transfer catalysis conditions technique

Article abstract of DOI:10.1002/jhet.1786

Heterocyclization reaction of 1-phenylpyrazolidine-3,5-dione with some active nitriles and acrylonitriles is described. These cyclization reactions afforded novel heterocyclic derivatives such as pyrano[2,3-c]pyrazoles, pyrazolyl-thiazole, pyrazolyl-1,3-t

Full text of DOI:10.1002/jhet.1786

Month 2014
The Reaction of 1-Phenylpyrazolidine-3,5-dione with Active Nitriles
Using Phase Transfer Catalysis Conditions Technique
*
A. Khodairy and A. M. El-Sayed
Department of Chemistry, Faculty of Science, Sohag University, Egypt
*
E-mail: Khodairy@yahoo.com
Received April 2, 2012
DOI 10.1002/jhet.1786
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
EtO - C(R)=C(CN)X
EtO - C(R)=C(CN)X
HN
O
N
Dioxane /TEA/ ref. 3 hr
Methanol/ TEA / ref. 2 hr or
Dioxane/ TEA / 0
Ph
1
X
R
R
O
X
O
N
HN
N
OH
NH
O
HN
N
Ph
Dioxane/ref. 1 hr
Ph
Heterocyclization reaction of 1-phenylpyrazolidine-3,5-dione with some active nitriles and acrylonitriles is
described. These cyclization reactions afforded novel heterocyclic derivatives such as pyrano[2,3-c]pyrazoles,
pyrazolyl-thiazole, pyrazolyl-1,3-thiazines, and pyrazolyl-1,3-oxathiino[6,5-c]pyrazoles. Heating
1-phenylpyrazolidine-3,5-dione alone under phase transfer catalysis conditions afforded the tricyclic
dipyrazolofurandione. The structure of the new products has been characterized by IR, NMR, mass
spectra, and their elemental analyses.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
give pyrano[2,3-c]pyrazole-5-carbonitriles 3a,b and ethyl
pyrano[2,3-c]pyrazole-5-carboxylate 3c, respectively, in
good yield. Compounds 3a–c were obtained directly via
the reaction of compound 1 with the same reagents in
refluxing dioxane, containing triethylamine as a catalyst
(cf. Scheme 1). IR spectra of compounds 2a–c showed
appearance of new absorption bands corresponding to CN
3,5-Pyrazolidendiones[1–4] were reported to possess
antibacterial, anti-inflammatory[5], antiviral[6], antimicro-
bial[7] and uricosuria properties[8]. Pyranopyrazoles[9],
1,3-thiazines[10], thiazoles [11], thienopyrazoles [12],
and furopyrazole [13] represent important classes of
heterocycles, which have been developed for different
purposes in the pharmaceutical field. In continuation of
our previous works, which had dealt with using active
nitriles in synthesis of polyfused- and spiropyrazoles
[14–21], herein, we report the synthesis of pyrano[2,3-c]
pyrazole, thiazole, 1,3-thiazine, 1,3-oxothiinopyrazole,
and furo[2,3-c]pyrazole derivatives starting with 1-
phenylpyrazolidine-3,5-dione[1–4,10,14].
groups and C═Oester at n2220–2208 cmꢀ1 and 1705 cmꢀ1
,
respectively, whereas IR spectra of compounds 3a–c
revealed the absence of one of the absorption bands
corresponding to C═O group at position-5 of compound 1
and showed absorption bands corresponding to NH groups
1
at n 3282–3230 cmꢀ1. H NMR spectrum of compounds
3a–c showed new signals corresponding to NH groups at
d 10.30 and 8.20ppm, ═CH at d 6.10ppm, methyl
group at d 2.20 ppm and ester group at d 4.40–4.00 and
1.30–1.00 ppm, respectively. MS spectra of compounds 2b,
3a, 3b, and 3c showed the molecular peak ions at 266
(23%), 252 (34%), 266(7.4%), and 299(65.5%), respec-
tively. The reaction pathway was assumed to proceed
through the nucleophilic addition of the formed carbanion
at position-4 of compound 1 on the C═C group of the nitrile
reagent with elimination of ethanol molecule to give 2a–c.
The subsequent step is the addition of the tautomeric OH
[14,16–18] to the CN group in all cases forming the
corresponding pyranopyrazoles 3a–c.
RESULTS AND DISCUSSION
The reaction of 1-phenylpyrazolidine-3,5-dione[10]
(1) with ethoxymethylenemalononitrile, 1-ethoxyethyli-
denemalononitrile or ethyl 2-cyano-3-ethoxyacrylate in
refluxing methanol or at 0oC in dioxane, afforded [(3,
5-dioxo-1-phenylpyrazolidin-4-yl)methylene]-malononitrile
(2a), 1-[(3,5-dioxo-1-phenylpyrazolidin-4-yl)ethylidene]
malononitrile (2b) and ethyl [(3,5-dioxo-1-phenylpyra-
zolidin-4-yl)methylene]cyanoacetate (2c), respectively.
These compounds were cyclized in refluxing dioxane to
© 2013 HeteroCorporation

A. Khodairy and A. M. El-Sayed
Vol 000
Scheme 1
O
EtO - C(R)=C(CN)X
EtO - C(R)=C(CN)X
HN
O
N
Methanol/ TEA / refluxe 2 hr or
Dioxane/ TEA / 0 Degree
Dioxane /TEA/ refluxe 3 hr
Ph
1
X
R
R
O
X
O
N
HN
OH
N
NH
O
HN
N
Ph
Dioxane/ refluxe 1 hr
Ph
2
3
2a, 3a; R = H, X = CN
2 b,3 a; R = CH3, X = CN
2c, 3c ; R = H, X = COOEt
The resulting mixture of compound 1 and phenylisothio-
cyanate was treated with phenacyl bromide, (1-ethoxyethy-
lidene)malononitrile or ethyl 2-cyano-3-ethoxyacrylate in
1: 1: 1 M ratio under phase transfer catalysis conditions
(PTC) [K2CO3/tetrabutylammonium bromide (TBAB)/
dioxane] to afford the corresponding thiazole 4 and 1,
3-thiazines 5a,b derivatives, respectively (cf. Scheme 2).
1H NMR spectrum of compound 5a showed new signals
corresponding to NH group at d 8.50 ppm, methyl group
at d 2.23 ppm in addition to aromatic protons and NH
group at d 7.80–6.70 ppm. MS spectra of compounds 4
and 5a gave the molecular ion peaks at 397 (7%) and
401 (2%), respectively. Khodairy[14] reported that the
reaction of compound 1 with a mixture of phenylisothio-
cyanate and benzylidenemalononitrile in refluxing pyridine
gave 1,4-dioxo-2,8-diphenyl-6-(phenylimino)-10-imino-
7-thia-2,3-diazaspiro[4.5]dec-8-ene-9-carbonitrile in 60%
yield. But we report here the reaction of compound 1 with
the same reagents under PTC conditions, gave the
corresponding 4-imino-1,3-thiazine-5-carbonitrile deriva-
tive 6a in 90% yield. Mass spectrum of compound 6a
showed the molecular ion peak at 463 (2%). In analogy,
treatment of compound 1 with phenyl isothiocyanate
and ethyl benzylidenecyanoacetate under PTC conditions
afforded ethyl 4-imino-1,3-thiazine-5-carboxylate 6b (cf.
thioxo-1,2,3,4-tetrahydro[1,3]oxa-thiino[6,5-c]-pyrazol-6-yl)
malononitrile (7a) or ethyl 2-cyano-2(3-oxo-1-phenyl-
4-thioxo-2,3,4,6-tetrahydro-[1,3]oxathiino[6,5-c]pyrazol-6-yl)
carboxylate (7b) were obtained, respectively (cf. Scheme 3).
The IR spectra of compounds 7a,b revealed the absence of
the absorption band corresponding to C═O group at posi-
tion-5 of compound 1 and appearance of new absorption
bands corresponding to CN, C═Oester and C═S groups at n
1
2203, 1710, and 1150 cmꢀ1, respectively. Their H NMR
spectra showed the absence of the signal corresponding to
CH2 group of compound 1 and appearance of new signals
corresponding to CH and ester groups.
Unexpectedly, stirring of compound 1 alone under PTC
conditions [K2CO3/TBAB/dioxane] afforded pyrazolo
[30,40:4,5]furo[2,3-c]pyrazol-3,7-dione 8 (Scheme 4) in
1
83% yield. Its H NMR spectrum showed new signals
corresponding to two methane groups at 3.30–3.10 ppm.
as dd, J = 7.20 Hz., whereas the 13C NMR spectrum
showed signals at 72 and 50 ppm characteristics for C4
and C8, respectively. Its mass spectrum showed the
molecular ion peak at 334(6%).
EXPERIMENTAL
All reagents and solvents were of commercial quality; solvents
were dried according to standard procedures when deemed necessary.
All melting points are uncorrected and were recorded on Melt-Temp II
melting point apparatus. IR spectra were measured as KBr pellets on a
Shimadzu DR-8001 spectrometer. 1H-NMR spectra were recorded on
a Varian Gemini at 200 MHz using TMS as an internal reference and
DMSO-d6 as a solvent. Mass spectra were performed on a Shimadzu
GCMS-QP 1000 mass spectrometer at 70 ev. The elemental analyses
were carried out on a Perkin-Elmer 240oC Microanalyzer. All
compounds were checked for their purity on TLC plates.
1
Scheme 2). H NMR spectrum of compound 6b showed
ethyl ester protons at d 4.40–4.10 and 1.30–1.00 ppm
and NH proton at d 8.80–8.60 ppm as a broad signal
(D2O exchangeable).
Also, compound 1 was allowed to react with a mixture
of carbon disulfide and ethoxymethylenemalononitrile or
ethyl 2-cyano-3-ethoxyacrylate under PTC conditions
[K2CO3/(TBAB)/dioxane] where, 2(3-oxo-1-phenyl-4-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
The Reaction of 1-Phenylpyrazolidine-3,5-dione with Active Nitriles Using Phase
Transfer Catalysis Conditions Technique
Scheme 2
Ph
Ph
Ph
HO
N
Ph
NH
S
O
S
PhCOCH Br
2
O
HN
O
- HBr
N
- H2O
HN
O
N
Ph
Ph
4
Ph
O
NH
HN
N
Y
-
+
S K
Ph
X
PhNCS
PTC
Y
S
O
N
HN
1
O
EtO - C(X)C=C(CN)Y
N
Ph
O
HN
X = CH3, Y = CN
X = H, Y = COOEt
O
NH
N
X
S
Ph
5
HN
O
N
Ph
5a, X = CH3 , Y= CN
5b, X = H , Y = COOEt
N
X
Ph
O
NH
HN
N
X
Ph
Ph
S
PhCH=CX(CN)
PTC
Ph
S
O
HN
O
N
Ph
HN
O
N
Ph
- H2
HN
X
Ph
O
N
Ph
S
HN
O
N
Ph
6 a,b
6a, X = CN
6b, X = COOEt
Synthesis of compounds 2a–c
product so formed on hot was filtered off, dried, and crystallized
from the appropriate solvent.
Procedure A. A mixture of 1-phenylpyrazolidine-3,5-dione 1
(0.01 mol, 1.76g) and ethoxymethylenemalononitrile (0.01 mol,
1.22 g), (1-ethoxyethylidene)malononitrile (0.01mol, 1.36g) or
ethyl 2-cyano-3-ethoxyacrylate (0.01 mol, 1.69 g) and TEA
(0.2mL) was refluxed in methanol (20 mL) for 2 h. The solid
Procedure B. A mixture of 1-phenylpyrazolidine-3,5-dione
1 (0.01 mol, 1.76 g) and ethoxymethylenemalononitrile (0.01 mol,
1.22 g), (1-ethoxyethylidene)malononitrile (0.01 mol, 1.36 g) or
ethyl 2-cyano-3-ethoxyacrylate (0.01 mol, 1.69 g) and TEA
Scheme 3
S
S
O
S
S
X
N
N
SH
O
S
O
CS2
PTC
HN
O
EtOCH=C(CN)X
N
1
HN
OH
HN
- H2O
X
N
Ph
- EtOH
N
OH
7 a,b
7a, X = CN
7b, X = COOEt
Ph
Ph
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Khodairy and A. M. El-Sayed
Vol 000
Scheme 4
H
N
O
O
Ph
HO
N
NH
O
- Q+
O
N
O
O
O
K2CO3
Q+ Br-
Ph
HN
HN
HN
N
O
O
N
N
Ph
Ph
Ph
K2CO3
Q+ Br-
H
N
O
Ph
N
H
N
O
O
Ph
-
N
- OH-
- Q+
HO
O
HN
OH
N
HN
Ph
OH
N
K2CO3
Q+ Br-
Ph
Ph
H
N
N
H
H
N
O
O
Ph
O
H
N
O
HN
O
N
HN
-
+
Ph
O Q
N
8
Ph
(0.2 mL) was stirred in dioxane (15 mL) at 0ꢁC for 2 h. The solid
product so formed was filtered off, dried, and crystallized from
(0.01 mol, 2.99 g) in dioxine (20 mL) containing TEA (0.2 mL)
was refluxed for 1 h. The reaction mixture was left to cool and
poured into crushed ice; the separated solid was filtered off,
the appropriate solvent.
[(3,5-Dioxo-1-phenylpyrazolidin-4-yl)methylene]malononitrile
dried, and crystallized.
(2a). Yellow crystals from ethanol, yield (59%); mp 270–2ꢁC; IR
Procedure B. A mixture of 1-phenyl-3,5-pyrazolidindione
1
(KBr) n cmꢀ1 : 3240 (NH), 2220 (CN), 1672, 1636 (2C═O). H
(0.01 mol, 1.76 g) and ethoxymethylenemalononitrile (0.01 mol,
1.22 g), (1-ethoxyethylidene) malononitrile (0.01 mol, 1.36 g), or
2-cyano-3-ethoxyacrylate (0.01 mol, 1.69) in dioxane (20 mL)
containing TEA (0.2 mL) was refluxed for 2 h and then left to
cool. The solid product so formed was filtered off, dried, and
NMR (DMSO-d6) d ppm: 9.00 (s, 1H, exchangeable with D2O,
NH); 8.30–8.00 (br, 1H, CH═); 7.97–6.90 (m, 5H, Harom.);
4.20–4.00 (d, J= 11.2 Hz, 1H, CHpyrazole). Found, %: C, 61.76; H, 3.32;
N, 22.40. C13H8N4O2 (252.22). Calcd. %: C, 61.90; H, 3.20; N, 22.21.
[1(3,5-Dioxo-1-phenylpyrazolidin-4-yl)ethylidene]malononitrile
crystallized from the appropriate solvent.
(2b). Yellow crystals from ethanol, yield (79%); mp 278ꢁC; IR
6-Imino-3-oxo-1-phenyl-1,2,3,6-tetrahydropyrano[2,3-c]-
1
(KBr) n cmꢀ1 : 3154 (NH), 2208 (CN), 1678, 1634 (2C═O). H
pyrazole-5-carbonitrile (3a). White crystals from ethanol, yield
(69%); mp 300–2ꢁC; IR (KBr) n: 3282, 3220 (2NH), 2215 (CN),
1634 (C═ O). 1H NMR (DMSO-d6) d ppm: 8.70 (s, 1H,
exchangeable with D2O, NHpyrazole); 8.50 (s, 1H, exchangeable with
D2O, NH); 7.80–6.70 (m, 5H, Harom.); 6.00 (s, 1H, ═CH). 13C NMR
(d6-DMSO) d ppm: 150(C═O), 148(C═NH), 142, 134(CH═), 125,
122, 114(–CN), 111(C4), 100, 92(C–CN). MS (EI, 70 eV), m/z (Irel,
%): 252 (34), 251 (10), 181 (3), 146 (13), 133 (6), 119 (4), 91 (100),
77 (31), 64 (21), 51 (15). Found, %: 61.76; H, 3.32; N, 22.40
NMR(DMSO-d6) d ppm:9.40–9.20 (br, 1H, exchangeable with
D2O, NH); 7.80–6.70 (m, 5H, Harom.); 4.00 (s, 1H, CHpyrazole);
2.30 (s, 3H, CH3). MS (EI, 70 eV), m/z (Irel, %): 266 (23), 265
(100), 241 (2), 220 (3), 201 (4.6), 175 (19), 103 (14), 83 (34).
Found, %: C 63.30; H 3.50; N 21.23. C14H10N4O2 (266.25).
Calcd. %: C, 63.15; H, 3.79; N, 21.04.
Ethyl [(3,5-dioxo-1-phenylpyrazolidin-4-yl)methylene]
cyanoacetate (2c). Green crystals from ethanol, yield (85%); mp
223–5ꢁC; IR (KBr) n 3240(NH), 2211(CN), 1705 (C═Oester ),
1672, 1636 (2C═O). 1H NMR (DMSO-d6) d ppm:8.70 (s, 1H,
exchangeable with D2O, NH); 8.20–8.00 (d, J= 10.6 Hz, 1H, ═CH);
7.90–6.80 (m, 5H, Harom.); 4.40–4.00 (m, 3H, CH2ester +CHpyrazole);
1.30–1.00(t, J= 5.1 Hz, 3H, CH3). Found, %: C, 60.33; H, 4.54; N,
14.21. C15H13N3O4 (299.28). Calcd. %: C, 60.20; H, 4.38; N, 14.04.
Synthesis of compounds 3a–c
C13H8N4O2 (252.22). Calcd. %: C, 61.90; H, 3.20; N, 22.21.
6-Imino-4-methyl-3-oxo-1-phenyl-1,2,3,6-tetrahydropyrano
[2,3-c]pyrazole-5-carbonitrile (3b).
Brown crystals from
ethanol, yield (79%); mp 245–7; IR (KBr) n, 3230, 3150(2NH),
2218(CN), 1624 (C═O). 1H NMR (DMSO-d6), d ppm: 8.50
(s, 1H, exchangeable with D2O, NHpyrazole); 7.80–6.60 (m, 6H,
Harom. + NH); 2.20 (s, 3H, CH3). MS (EI, 70 eV), m/z (Irel, %):
266 (7.4), 262 (18), 242 (14), 224 (21), 196 (30), 193 (70), 186
(100), 178 (17), 135 (24), 85 (45), 60 (80). Found, %: C, 63.30;
Procedure A.
A suspension of compound 2a (0.01 mol,
2.52 g), compound 2b (0.01 mol, 2.66 g), or compound 2c
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
The Reaction of 1-Phenylpyrazolidine-3,5-dione with Active Nitriles Using Phase
Transfer Catalysis Conditions Technique
H, 3.50; N, 21.23 C14H10N4O2 (266.25). Calcd. %: C, 63.15; H,
3.79; N, 21.04.
d, ppm: 8.70–8.50 (br, exchangeable with D2O, 1H, NH); 8.40–8.20
(br, 1H, exchangeable with D2O, NHpyrazole); 7.90–6.80 (m, 15H,
Harom.). MS (EI, 70 eV), m/z (Irel, %): 463 (2), 428 (1), 392 (5), 367
(6), 308 (64), 292 (31), 276 (15), 262 (25), 216 (32), 174 (20),
158 (3), 118 (13), 85 (100). Found, %: C, 67.10; H, 3.54; N, 15.32;
S, 6.80. C26H17N5O2S (463.51). Calcd. %: C, 67.37; H, 3.70;
Ethyl 6-imino-3-oxo-1-phenyl-1,2,3,6-tetrahydropyrano[2,3-c]
pyrazole-5-carboxylate (3c). Yellow crystals from ethanol, yield
(80%); mp 320–2ꢁC; IR (KBr) cmꢀ1, n: 3301, 3150 (2NH), 1710
(COester), 1630 (C═O). 1H NMR (DMSO-d6) d ppm: 8.70 (s, 1H,
exchangeable with D2O, NHpyrazole); 8.10 (s, 1H, exchangeable
with D2O, NH); 7.90–6.90 (m, 5H, Harom.); 6.00 (s, 1H, ═CH);
4.40–4.00 (q, J = 4.1 Hz 2H, CH2); 1.30–1.00 (t, J = 4.9 Hz, 3H,
CH3). MS (EI, 70 eV), m/z (Irel, %): 299 (65.5), 298 (38.6), 253
(59.3), 252 (62.6), 187 (8.5), 186 (9.3), 182 (2.4), 164 (8.9), 154
(2.4), 137 (6.5), 128 (5.3), 119 (5.7), 105 (14.6), 91 (100), 77
(89). Found, %: C, 60.43; H, 4.50; N, 14.33. C15H13N3O4
(299.28). Calcd. %: C, 60.20; H, 4.38; N, 14.04.
N, 15.11; S, 6.92.
Ethyl 2-(3,5-dioxo-1-phenylpyrazolidin-4-yliden)-4-imino-3,6-
diphenyl-3,4-dihydro-2H- 1,3-thiazine-5-carboxzlate (6b).
White crystals from ethanol, yield (83%); mp 200–2ꢁC. IR (KBr)
n cmꢀ1: 3229, 3220 (2NH), 1710(COester), 1670, 1642 (2C═O).
1H NMR (DMSO-d6) d ppm: 8.70–8.40 (br, 1H, exchangeable
with D2O, NH); 8.20–8.60 (br, 1H, exchangeable with D2O,
NHpyrazole); 7.90–6.80 (m, 15H, Harom.); 4.40–4.10 (q, J = 4.6 Hz,
2H, CH2); 1.30–1.00 (t, J = 4.9 Hz, 3H, CH3). 13C NMR (d6-
DMSO) d ppm 164 (C═O position-5), 161(C═O position-3), 148
(C═NH), 145(C–Ph), 142, 139, 131, 130, 126, 124, 120(C–
COOEt), 102(C4), 60(CH2), 14(CH3). Found, %: C, 65.60; H,
4.50; N, 10.70; S, 6.28. C28H22N4O4S (510.56). Calcd. %: C,
65.86; H, 4.34; N, 10.97; S, 6.28.
Synthesis of compounds 4–6
General procedure.
A mixture of compound 1 (0.01 mol,
1.76 g), phenylisothiocyanate (0.01 mol, 1.3 mL), anhydrous
potassium carbonate (3 g), TBAB (0.003 g), and dioxane
(20 mL) was stirred for 2 h. at 60ꢁC. To the reaction mixture,
phenacyl bromide (0.01 mol, 1.99 g), (1-ethoxyethylidene)
malononitrile (0.01 mol, 1.36 g), 2-cyano-3-ethoxyacrylate
(0.01 mol, 1.69), benzylidenemalononitrile (0.01 mol, 1.54 g) or
ethyl benzylidenecyanoacetate (0.01 mol, 2.01 g) was added,
then the reaction mixture was stirred for 3 h at 60ꢁC until the
completion of the reaction (TLC). The reaction mixture was
filtered off and the filtrate was evaporated in vacuo. The residue
was triturated with pet. ether (40–60ꢁC), the separated solid was
Synthesis of compounds 7a,b
General procedure.
A mixture of compound 1 (0.01 mol,
1.76 g), carbon disulfide (0.01 mol, 0.76 ml), anhydrous
potassium carbonate (3 g), TBAB (0.003 g), and dioxane
(20 mL) was stirred for 2 h. at 60ꢁC. To the reaction mixture,
ethoxymethylenemalononitrile (0.01 mol, 1.22 g) or ethyl 2-
cyano-3-ethoxyacrylate (0.01 mol, 1.61 g) was added, then the
reaction mixture was stirred for 3 h at 60ꢁC until the completion
of the reaction (TLC). The reaction mixture was filtered off and
the filtrate was evaporated in vacuo. The residue was triturated
with pet. ether (40–60ꢁC), the separated solid was crystallized
crystallized from the appropriate solvent to give compounds 4–6.
2-(3,5-Dioxo-1-phenylpyrazolidin-4-ylidene)-3,4-diphenyl-1,3-
thiazole (4).
Amber yellow crystals from acetic acid, yield
(60%); mp 138–140ꢁC IR (KBr) n, cmꢀ1: 3240 (NH), 1675,
1
1641 (2C═O). H NMR (DMSO-d6) d ppm: 7.90–6.70 (m, 16H,
from the appropriate solvent to give compounds 7a,b.
Harom. + NHpyrazole); 5.50 (s, 1H, ═CH). 13C NMR (d6-DMSO)
d ppm: 163 (C═O position-5), 160 (C═O position-3), 142, 140
(C-Ph), 133, 130, 125, 123(=CH), 120, 97. MS (EI, 70eV), m/z
(Irel, %): 397 (7), 387 (5), 228 (5), 210 (4), 197 (7), 194 (17), 180
(19), 135 (100), 105 (88), 93 (68), 77(76). Found: C, 70.24; H,
4.30; N, 10.31; S, 7.90. C24H17N3O2S (411.47). Calcd. %: C,
2(3-Oxo-1-phenyl-4-thioxo-1,2,3,4-tetrahydro[1,3]oxathiino
[6,5-c]pyrazol-6-yl)-malononitrile (7a).
Light brown crystals
from dioxane, yield (60%); mp 234–6ꢁC. IR (KBr) n, cmꢀ1: 3222
1
(NH), 2203 (CN), 1638 (C═O). H NMR (CDCl3) d ppm: 8.30
(s, 1H, exchangeable with D2O, NHpyrazole); 7.40–6.80 (m, 5H,
Harom.); 5.30 (d, J = 9.1 Hz, 1H, CH oxathiine); 3.50 (d, J = 9.7 Hz,
1H, CH). Found, %: C, 51.45; H, 2.65; N, 17.30; S, 19.78.
C14H8N4O2S2 (328.36). Calcd. %: C, 51.21; H, 2.46; N, 17.06;
70.05; H, 4.16; N, 10.21; S, 7.79.
2-(3,5-Dioxo-1-phenylpyrazolidin-4-yliden)-4-imino-6-methyl-
3-phenyl-3,4-dihydro-2H-1,3-thiazine-5-carbonitrile (5a). Yellꢀow1
S, 19.53.
crystals from benzene, yield (85%); mp 300ꢁC. IR (KBr) n cm
:
Ethyl 2-cyano-2(3-oxo-1-phenyl-4-thioxo-2,3,4,6-tetrahydro
3282, 3220 (2NH), 2215 (CN), 1670, 1630 (2C═O). 1H NMR
(DMSO-d6) d ppm: 8.50 (s, 1H, exchangeable with D2O, NH);
8.00–6.90 (m, 6H, Harom. +NHpyrazole); 2.20 (s, 3H, CH3). MS (EI,
70 eV), m/z (Irel, %): 401 (2), 396 (1), 389 (2), 306 (4), 279 (9), 256
(14), 193 (28), 186 (42), 169 (7), 105 (6), 85 (41), 71(100). Found,
%: C, 62.66; H, 3.40; N, 17.70; S, 7.75. C21H15N5O2S (401.44).
[1,3]oxathiino-[6,5-c]-pyrazol-6-yl)carboxylate (7b).
Brown
crystals from benzene, yield (85%); mp 177–8ꢁC. IR (KBr) n,
cmꢀ1: 3220 (NH), 2211 (CN), 1710, 1638 (2C═O). 1H NMR
(DMSO-d6) d ppm: 8.30–8.00 (br, 1H, exchangeable with D2O,
NHpyrazole); 7.40–6.80 (m, 5H, Harom.); 5.40 (d, J = 10Hz, 1H, CH
oxathiine); 3.50 (d, J = 9.4 Hz, 1H, CH), 4.40–4.10 (q, J = 3.90 Hz,
2H, CH2); 3.60 (s, 1H, CH); 1.30–1.00 (t, J = 4.00 Hz 3H, CH3).
Found, %: C, 51.38; H, 3.65; N, 11.35; S, 17.22. C16H13N3O4S2
Calcd. %: C, 62.83; H, 3.77; N, 17.45; S, 7.99.
Ethyl l2-(3,5-Dioxo-1-phenylpyrazolidin-4-yliden)-4-imino-
3-phenyl-3,4-dihydro-2H-1,3-thiazine-5-carboxylate (5b). Amber
(375.42). Calcd. %: C, 51.19; H, 3.49; N, 11.19; S, 17.08.
yellow crystals from DMF, yield (90%); mp 217–9ꢁC. IR (KBr) n
1,5-Diphenyl-1,2,3a,5,6,7b-hexahydropyrazolo[3’,4’:4,5]furo
1
cmꢀ1: 3272, 3210 (2NH), 1710 (COester), 1673, 1636 (2C═O). H
[2,3-c]pyrazol-3,7-dione 8.
To a solution of compound 1
(0.01 mol, 1.76 g) in dioxane (20 mL), anhydrous potassium
carbonate (3 g), and TBAB (0.003 g) were added. The reaction
mixture was stirred for 3 h at 60ꢁC until the completion of the
reaction (TLC) and worked up as before. Yellow crystals from
DMF, yield (83%); mp 265–7ꢁC. IR (KBr) n, cmꢀ1: 3220
(NH), 1646 (C═O). 1H NMR (DMSO-d6) d ppm: 8.30–8.10 (br,
2H, exchangeable with D2O, 2NHpyrazole); 7.30–6.70 (m, 10H,
Harom.); 3.30–3.10 (dd, J = 7.20 Hz, 2H, 2CH). 13C NMR (d6-
DMSO) d, ppm: 170 (C═O), 166 (═C–O), 160 (C═O), 138,
NMR (DMSO-d6) d, ppm: 8.60 (s, 1H, exchangeable with D2O,
NH); 8.10–6.60 (m, 11H, Harom. +NHpyrazole); 5.30 (s, 1H, ═CH);
4.40–4.10 (q, J=4.1Hz, 2H, CH2); 1.30–1.00 (t, J= 5 Hz, 3H, CH3).
Found, %: C, 60.61; H, 4.30; N, 12.70; S, 7.50. C22H18N4O4S
(434.46). Calcd. %: C, 60.82; H, 4.18; N, 12.90; S, 7.38.
2-(3,5-Dioxo-1-phenylpyrazolidin-4-yliden)-4-imino-3,6-diphenyl-
3,4-dihydro-2H-1,3-thiazine-5-carbonitrile (6a). Colorless crystals
from acetic acid, yield (90%); mp 240–2ꢁC. IR (KBr) n cmꢀ1: 3330,
3220 (2NH), 2100 (CN) 1670, 1640 (2C═O). 1H NMR (DMSO-d6)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Khodairy and A. M. El-Sayed
Vol 000
[9] Pavlik, J. W.; E-yasuporn, J. W.; MacDonald, V. J. C.;
Yanone, S. T. Arkivoc 2009, VIII, 57.
[10] Rathod, S. P.; Charjon, A. P.; Rajput, P. R. Rasayan J Chem
2010, 3, 363.
[11] Hassan, S. M.; Abdel-Aal, M. M.; El-Maghraby, A. A.;
Bashandy, M. S. Phosphorus, Sulfur, Silicon, Relat Elem 2009,
184, 427.
132, 128, 125, 124, 123, 120, 118, 110, 89, 72 (C4), 50 (C8). MS
(EI, 70 eV), m/z (Irel, %): 334 (6), 313 (4), 279 (10), 256 (36),
236 (13), 205 (18), 167 (35), 149 (100), 129 (20), 112 (25), 97
(63), 83 (48). Found, %: C, 64.40; H, 4.41; N, 16.55.
C18H14N4O3 (334.32). Calcd. %: C, 64.66; H, 4.22; N, 16.76.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet