A convenient synthesis of some pyrazolinone and pyrazole derivatives

Article abstract of DOI:10.1002/jccs.200400146

A convenient synthesis of some novel 6-amino-4-aryl-1-phenyl-3-pyridin-4- yl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles (3a,b) and 5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbaldehyde (4) is described. Compound 4 was obtained by the reaction of 2-phenyl-5-pyridin-4-yl-2,4- dihydropyrazol-3-one (1) with dimethylformamide and phosphorus oxychloride under Vilsmeier-Haack reaction conditions. Compound 4 was subjected to react with different reagents such as hippuric acid, sodium azide and aromatic ketones to afford 4-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazolo-4-ylmethylene)-2-phenyl-4 H-oxazol-5-one(5), 5-azido-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-carbaldehyde (8) and 1-aryl-3-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)propenones (12a,b), respectively. The latter compounds were also prepared via Michael reaction by treatment of compound 1 with some different chalcones.

Full text of DOI:10.1002/jccs.200400146

Journal of the Chinese Chemical Society, 2004, 51, 983-990
983
A Convenient Synthesis of Some Pyrazolinone and Pyrazole Derivatives
El-Saied A. Aly,* Mohamed A. Abdo and Atif A. El-Gharably
Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt
A convenient synthesis of some novel 6-amino-4-aryl-1-phenyl-3-pyridin-4-yl-1,4-dihydropyrano[2,3-
c]pyrazole-5-carbonitriles (3a,b) and 5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbaldehyde (4) is
described. Compound 4 was obtained by the reaction of 2-phenyl-5-pyridin-4-yl-2,4-dihydropyrazol-3-one
(1) with dimethylformamide and phosphorus oxychloride under Vilsmeier-Haack reaction conditions. Com-
pound 4 was subjected to react with different reagents such as hippuric acid, sodium azide and aromatic ke-
tones to afford 4-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazolo-4-ylmethylene)-2-phenyl-4H-oxazol-5-
one (5), 5-azido-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-carbaldehyde (8) and 1-aryl-3-(5-chloro-1-phenyl-
3-pyridin-4-yl-1H-pyrazol-4-yl)propenones (12a,b), respectively. The latter compounds were also prepared
via Michael reaction by treatment of compound 1 with some different chalcones.
Keywords: 2,4-Dihydropyrazol-3-one; Dimethylformamide; Vilsmeier-Haack reaction; Phase-transfer
catalysis (PTC); Knoevenagel condensation; Michael reaction; Chalcones.
INTRODUCTION
In recent years, pyrazolinones either alone or as a fused
hydes (benzaldehyde and p-anisaldehyde) to give 4-aryl-
idine-2-phenyl-5-pyridin-4-yl-2,4-dihydropyrazol-3-ones
(2a,b) which when reacted with malononitrile in dry benzene
and in the presence of triethylamine afforded 6-amino-4-
aryl-1-phenyl-3-pyridin-4-yl-1,4-dihydropyrano[2,3-c]pyr-
azole-5-carbonitriles (3a,b) (Scheme I).
ring with other heterocyclic moieties have been synthesized
to be used as analgesic,1,2 anti-mycobacterial,3-5 anti-inflam-
matory6 and anti-microbial agents,7 and also as drugs for the
treatment of neonatal hypoxic-ischemic encephalopathy.8
This encourages us to continue our previous studies9 on the
pyrazolinone series. The starting material 2-phenyl-5-pyri-
din-4-yl-2,4-dihydropyrazol-3-one (1) was prepared accord-
ing to literature procedures.10
Reaction of compound 1 with dimethylformamide in
the presence of phosphorus oxychloride under Vilsmeier-
Haack reaction conditions11 gave 5-chloro-1-phenyl-3-pyr-
idin-4-yl-1H-pyrazole-4-carbaldehyde (4), which was sub-
jected to react with different reagents such as hippuric acid in
the presence of acetic anhydride and sodium acetate to give
4-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-ylmeth-
ylene)-2-phenyl-4H-oxazol-5-one (5). The oxidation of the
formyl group in compound 4 by potassium permanganate un-
der the condition of phase-transfer catalysis (PTC)12 gave
RESULTS AND DISCUSSION
Compound 1 was condensed with some aromatic alde-
Scheme I
N
N
N
H
Ar
CH-Ar
O
CN
ArCHO
CH2(CN)2
N
N
N
Et3N, benzene
O
N
N
N
O
NH2
Ph
Ph
1
Ph
2a,b
3a,b
a, Ar = C6H5
b, Ar = 4-CH3OC6H4
* Corresponding author. E-mail: esali@masrawy.com

984 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Aly et al.
5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carboxylic
acid (6), which on esterification with ethyl alcohol afforded
the corresponding ethyl ester 7 (Scheme II).
Scheme II
N
N
O
Treatment of compound 4 with excess sodium azide in
DMSO at 110 °C gave the two products 5-azido-1-phenyl-3-
pyridin-4-yl-1H-pyrazole-4-carbaldehyde (8) and 5-hydro-
xy-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbonitrile (9).
However compound 8 was obtained as a sole product by
warming compound 4 with sodium azide at 40 °C. Also, com-
pound 8 was converted to compound 9 by heating under re-
CHO
Cl
CH2COOH
NHCOPh
CH
O
POCl3
DMF
1
N
N
N
Cl
N
AcOH, AcONa
N
Ph
Ph
Ph
5
4
KMnO4
PTC
N
1
N
flux in toluene. Elemental analyses, IR and H NMR data
confirmed the structure of 9. The IR spectrum proved the ap-
pearance of CN and OH groups. 1H NMR spectrum showed
the appearance of an OH group at 9.10 ppm in compound 9
which was not noted in the spectrum of compound 8.
COOEt
Cl
COOH
EtOH, H+
N
N
Cl
N
N
Ph
Ph
6
On the other hand, treatment of compound 8 with hy-
drazine hydrate in the presence of acetic acid in ethanol under
7
Scheme III
N
N
CN
CHO
110 oC
N
N
+
OH
N3
N
N
Ph
Ph
8
9
Toluene, reflux
NaN3, DMSO
N
4
AcOH, EtOH
reflux
N
N
N
H
N
NH2NH2.H2O
40oC
Ph
8
10
N
I2, R.T.
N
O
NH2
N
CH=CH
Cl
C
Ar
N
N
N
CH3COAr
N
Ph
N
11
Ph
12a,b
a, Ar = C6H5
b, Ar = 4-CH3C6H4

Synthesis of Pyrazolinone and Pyrazole Derivatives
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 985
Scheme IV
O
OCH3
CH=CH
OCH3
C
Ar
OCH3
N
N
N
O
Ar
N
N
+
N
N
N
O
OH
N
Ph
Ph
Ph
13
14
a, Ar = C6H5-
b, Ar = 4-CH3C6H4
EtOH
1
piperidine
Ph
N
Ph
N
N
N
N
N
Cl
Cl
N
N
N
O
12b
N
N
N
+
N
N
N
OH
O
CH3
Ph
Ph
Ph
15
16
reflux yielded 1-phenyl-3-pyridin-4-yl-1,6-dihydropyra-
zolo[3,4-c]pyrazole (10), but on treatment with hydrazine hy-
drate at room temperature in the presence of iodine afforded
6-phenyl-4-pyridin-4-yl-6H-pyrazolo[3,4-c]pyrazol-2-yl-
amine (11). N3 Band at 2162 cm-1 in compound 8 disappeared
product with the two chalcones, while the cold concentrated
mother liquors of the two reactions gave the desired 1-aryl-3-
(5-hydroxy-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-3-(4-
methoxyphenyl)propan-1-ones (14a,b).
On the other hand, the reaction of compound 1 with the
chalcone 12b gave 4-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-
pyrazol-4-yl)-1,7-diphenyl-3,5-dipyridin-4-yl-4,7-dihydro-
1H-pyrano[2,3-c; 6,5-c¢]dipyrazole (15) and the expected
3-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-3-(5-
hydroxy-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-1-(4-
methylphenyl)propan-1-one (16) was isolated through con-
centration and cooling of the mother liquor (Scheme IV).
Formation of compounds 13 and 15 may proceed ac-
cording to the following mechanism (Scheme V).
1
in the IR spectra of compounds 10 and 11 whereas their H
NMR spectra showed the existence of a NH signal at 13.90
ppm of compound 10 and NH2 signal at 6.00 ppm of com-
pound 11 which disappeared by deutration.
Moreover, applying Knoevenagel condensation13 on
compound 4 with acetophenone and/or 4-methylacetophe-
none led to chalcones 1-phenyl or 1-(4-methylphenyl)-3-(5-
chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)propenones
1
(12a,b) (Scheme III). From H NMR spectra, compounds
12a,b exist in the stable trans form (CH=CH, J = 16.3 Hz for
12a and J = 16.1 for 12b).
Finally Michael reaction was applied on compound 1
with different chalcones such as 1-phenyl or 1-(4-methyl-
phenyl)-3-(4-methoxyphenyl)propenones in ethanol and in
the presence of piperidine under reflux to afford 4-(4-meth-
oxyphenyl)-1,7-diphenyl-3,5-dipyridin-4-yl-4,7-dihydro-
1H-pyrano[2,3-c; 6,5-c¢]dipyrazole (13) as a precipitated
EXPERIMENTAL SECTION
All melting points are uncorrected; they were per-
formed by open capillary using an electrothermal melting
MEL-TEMP II apparatus. IR spectra were recorded with a
UNICAM SP1200 spectrometer using pellet technique KBr

986 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Aly et al.
Scheme V
N
N
N
O
H
H
Ar'
O
C
H
Ar'-CH=CH-C-Ar
H
+ :B
CH CH
Ar
N
N
N
- BH
O
O
O
N
N
N
Ph
Ph
Ph
4
N
N
Ar'
O
C
Ar'
O
C
H
- :B
+ BH
+ :B
CH CH2
O
Ar
CH CH2
O
Ar
- BH
N
N
N
N
Ph
Ph
N
N
N
N
Ar'
Ar'
O
H
H
CH
- CH2-C-Ar
CH
N
N
N
O
N
O
N
N
O
O
N
Ph
N
Ph
Ph
Ph
N
N
Ar'
- H2O
N
N
N
N
O
Ph
Ph
13, 15
discs. Microanalyses were preformed at the Microanalysis
Unit, Central Lab, Tanta University, Tanta, Egypt and Micro-
analyses Unit, Cairo University, Cairo, Egypt. 1H NMR spec-
tra were recorded with a Brüker spectrometer (400 MHz) us-
ing tetramethylsilane (TMS) as an internal reference, and the
chemical shift was expressed in d ppm values. Mass spectra
were recorded with a micromass spectrometer model 7070 at
an energy of 70 eV and inlet temperature of 90 °C.
9H, Ar-H). Anal. Calcd. for C14H11N3O (237.24) C, 70.87; H,
4.67; N, 17.71. Found C, 70.67; H, 4.64; N, 17.51%.
4-Arylidene-2-phenyl-5-pyridin-4-yl-2,4-dihydropyrazol-
3-ones (2a,b)
A mixture of compound 1 (2.37 g, 0.01 mol) and the ap-
propriate aldehyde (0.01) was fused in an oil bath at 140 °C
for 3 h. The reaction mixture was cooled and methyl alcohol
(5 mL) was added. The colored precipitate was filtered and
recrystallized from methanol.
2-Phenyl-5-pyridin-4-yl-2,4-dihydropyrazol-3-one (1)
A mixture of ethyl isonicotinyl acetate (1 g, 0.05 mol)
and phenylhydrazine (1 g, 0.01 mol) was heated in acetic acid
for 30 minutes at 100 °C, then poured onto ice/water. The yel-
low product that formed was collected by filtration and
washed with water several times and crystallized from ben-
zene. Yield 69%; mp 206-208 °C; IR (KBr) 3433, 1660, 1621
cm-1; 1H NMR (DMSO-d6) d 6.30 (s, 2H, CH2), 7.40-7.92 (m,
4-Benzylidene-2-phenyl-5-pyridin-4-yl-2,4-dihydropyrazol-
3-one (2a)
Yield 91%; mp 240-242 °C; IR (KBr) 1680, 1620, 1605
cm-1; 1H NMR (CDCl3) d 7.20-8.50 (m, 15H, Ar-H and =CH).
Anal. Calcd. for C21H15N3O (325.36) C, 77.52; H, 4.65; N,
12.91. Found C, 77.43; H, 4.63; N, 12.76%.

Synthesis of Pyrazolinone and Pyrazole Derivatives
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 987
4-(4-Methoxybenzylidene)-2-phenyl-5-pyridin-4-yl-2,4-
dihydropyrazol-3-one (2b)
(14), 248 (15), 220 (13), 77 (89), 51 (90). Anal. Calcd. for
C15H10ClN3O (283.90) C, 63.45; H, 3.55; N, 14.91; Cl, 12.49.
Found C, 63.87; H, 3.70; N, 14.24; Cl, 12.40%.
Yield 83%; mp 175-177 °C; IR (KBr) 1678, 1620, 1603
cm-1; 1H NMR (CDCl3) d 3.80 (s, 3H, OCH3), 7.20-8.80 (m,
14H, Ar-H and =CH). Anal. Calcd. for C22H17N3O2 (355.40)
C, 74.35; H, 4.82; N, 11.82. Found C, 74.13; H, 4.57; N,
11.68%.
4-(5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-ylmeth-
ylene)-2-phenyl-4H-oxazol-5-one (5)
An equimolar mixture of compound 4 and hippuric acid
(0.01 mol) was heated on a steam bath with addition of so-
dium acetate (0.05 mol) and acetic anhydride (0.3 mol) for 2 h
and then left to cool. Ethanol (20 mL) was added and it was
left overnight; the product that formed was collected by fil-
tration, washed with water (100 mL) and recrystallized from
ethanol. Yield 71%; mp 178-180 °C; IR (KBr) 1728, 1620,
1600 cm-1; 1H NMR (DMSO-d6) d 7.20-8.50 (m, 15H, Ar-H
and =CH); MS (EI) m/z (rel. intensity) 426 (61, M+), 427 (21,
M+ + 1), 428 (20, M+ + 2), 391 (15), 232 (2), 106 (80), 105
(71), 78 (100). Anal. Calcd. for C24H15ClN4O2 (426.86) C,
67.53; H, 3.54; N, 13.13; Cl, 8.30. Found C, 67.09; H, 3.84;
N, 13.31; Cl, 8.25%.
6-Amino-4-aryl-1-phenyl-3-pyridin-4-yl-1,4-dihydropyr-
ano[2,3-c]pyrazole-5-carbonitriles (3a,b)
A solution of malononitrile (0.002 mol) in dry benzene
(7 mL) and triethylamine (0.1 mL) was added to a stirred sus-
pension of 2a,b (0.001 mol) in dry benzene (5 mL). The start-
ing material was rapidly dissolved and a discolored solution
was formed. A white solid begins to separate within 10 min-
utes; stirring was continued for a further 3 h, and the colorless
precipitate was collected by filtration and recrystallized from
benzene.
6-Amino-1,4-diphenyl-3-pyridin-4-yl-1,4-dihydropyrano-
[2,3-c]pyrazole-5-carbonitrile (3a)
5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbox-
ylic acid (6)
Yield 66%; mp 228-230 °C; IR (KBr) 3336, 2190, 1605
cm-1; 1H NMR (DMSO-d6) d 4.50 (s, 1H, pyran-H), 7.20-8.60
(m, 14H, Ar-H), 8.70 (s, 2H, NH2). Anal. Calcd. for C24H17N5O
(391.43) C, 73.64; H, 4.38; N, 17.89. Found C, 73.50; H,
4.28; N, 17.96%.
A mixture of compound 4 (0.2 g, 0.00074 mol) and wa-
ter (15 mL) was placed in a 100 mL round-bottom flask, then
benzyl triethylammonium chloride (0.012 g, 0.33 mmol) was
added. The flask was immersed in a water bath preheated to
55 °C. A solution of potassium permanganate (0.16 g, 0.001
mol) in water (20 mL) was added dropwise over a period of
30 minutes with stirring and continuous heating for a further
2 h. A solution of potassium hydroxide was added, and the re-
sulting mixture was filtered to get rid of manganese dioxide.
The filtrate was acidified with dilute hydrochloric acid (1:1)
to pH = 3, and the separated product that appeared was col-
lected by filtration and recrystallized from ethanol. Yield
6-Amino-4-(4-methoxyphenyl)-1-phenyl-3-pyridin-4-yl-
1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3b)
Yield 67%; mp 193-195 °C; IR (KBr) 3341, 2195, 1610
cm-1; 1H NMR (DMSO-d6) d 3.50 (s, 3H, OCH3), 5.20 (s, 1H,
pyran-H), 6.80-8.20 (m, 13H, Ar-H), 8.70 (s, 2H, NH2). Anal.
Calcd. for C25H19N5O2 (421.45) C, 71.25; H, 4.54; N, 16.62.
Found C, 71.38; H, 4.78; N, 16.49%.
1
85%; mp 250-252 °C; IR (KBr) 3440, 1690, 1620 cm-1; H
5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbalde-
hyde (4)
NMR (DMSO-d6) d 7.60-8.70 (m, 9H, Ar-H), 11.20 (s, 1H,
COOH). Anal. Calcd. for C15H10ClN3O2 (299.90) C, 60.07;
H, 3.63; N, 14.07; Cl, 11.82. Found C, 59.97; H, 3.30; N,
13.67; Cl, 11.85%.
Compound 1 (4.8 g, 0.02 mol) was added to the cold
Vilsmeier reagent [prepared by addition of POCl3 (9.8 mL) to
DMF (17.8 mL)] and the reaction mixture was heated for 5 h
at 80 °C. The product that formed was poured onto ice-cold
water (100 mL) and treated with potassium carbonate till pH
= 9, then the separated yellow solid was filtered and recrys-
tallized from benzene.Yield 75%; mp 133-135 °C; IR (KBr)
Ethyl 5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-
carboxylate (7)
A mixture of 6 (2 g, 0.006 mol), absolute ethyl alcohol
(3 mL) and a few drops of concentrated sulphuric acid was
refluxed for four h. The excess alcohol was distilled off and
the resulting residue was poured onto water (20 mL), then
carbon tetrachloride was added and it was shaken in a sepa-
1
1682, 1605 cm-1; H NMR (CDCl3) d 7.20-8.90 (m, 9H,
Ar-H), 10.20 (s, 1H, CHO); MS (EI) m/z (rel. intensity) 283
(100, M+), 284 (38, M+ + 1), 285 (33, M+ + 2), 255 (6), 254

988 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Aly et al.
rating funnel. The resulting organic layer was shaken with a
saturated solution of sodium bicarbonate, then with water,
dried and the separated product that appeared was collected
by filtration. Yield 55%; mp 120-122 °C; IR (KBr) 1710,
1615 cm-1; 1H NMR (DMSO-d6) d 1.30 (t, 3H, CH3, J = 7.2
Hz), 4.40 (q, 2H, CH2, J = 7.2 Hz), 7.40-8.80 (m, 9H, Ar-H).
Anal. Calcd. for C17H14ClN3O2 (327.96) C, 62.26; H, 4.31; N,
12.87; Cl, 10.81. Found C, 62.40; H, 4.33; N, 12.53; Cl,
10.60%.
1-Phenyl-3-pyridin-4-yl-1,6-dihydropyrazolo[3,4-c]pyr-
azole (10)
A mixture of compound 8 (8.7 g, 0.03 mol), hydrazine
hydrate (25 mL) and acetic acid (2 mL) were heated under re-
flux in ethanol (125 mL) for 18 h. The cold mixture was
poured onto water, then extracted with methylene chloride (3
´ 200 mL). The extracted layers were collected, washed with
water and dried, then evaporated to give compound 10. Yield
1
67%; mp 275-277 °C; IR (KBr) 3290, 1610 cm-1; H NMR
(DMSO-d6) d 7.20-8.80 (m, 10H, Ar-H), 13.90 (s, 1H, NH).
Anal. Calcd. for C15H11N5 (261.29) C, 68.95; H, 4.24; N,
26.80. Found C, 68.85; H, 4.20; N, 26.42%.
Treatment of 4 with sodium azide
Method A: Formation of 8 and 9
A mixture of compound 4 (1.4 g, 0.005 mol) and so-
dium azide (0.4 g, 0.0065 mol) in DMSO (15 mL) was stirred
at 110 °C for 6 h. The reaction mixture was poured onto water
(50 mL); the separated precipitate was collected by filtration
and recrystallized from benzene to give 8. The resulting fil-
trate was acidified with 4 M hydrochloric acid till pH < 2 and
the solid product that formed was filtered, dried and recrys-
tallized from ethanol to give compound 9.
6-Phenyl-4-pyridin-4-yl-6H-pyrazolo[3,4-c]pyrazol-2-yl-
amine (11)
A mixture of compound 8 (5.8 g, 0.02 mol) and hydra-
zine hydrate (2.8 g) in ethanol (50 mL) containing a crystal of
iodine were set aside at room temperature for 2 h. The mix-
ture was poured onto water (200 mL) to give a yellow precipi-
tate which was collected by filtration and recrystallized from
toluene. Yield 78%; mp 320-322 °C; IR (KBr) 3364, 1605
cm-1; 1H NMR (CDCl3) d 7.20-8.80 (m, 10H, Ar-H), 6.00 (s,
2H, NH2). Anal. Calcd. for C15H12N6 (276.30) C, 65.21; H,
4.38; N, 30.41. Found C, 65.22; H, 4.28; N, 30.31%.
5-Azido-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbalde-
hyde (8)
Yield 39%; mp 160-162 °C; IR (KBr) 3190, 2162,
1
1667, 1601 cm-1; H NMR (DMSO-d6) d 7.10-8.60 (m, 9H,
Ar-H), 10.10 (s, 1H, CHO); MS (EI) m/z (rel. intensity) 290
(4, M+), 261 (5), 262 (19), 233 (3), 105 (24), 77 (100), 51
(24). Anal. Calcd. for C15H10N6O (290.28) C, 62.06; H, 3.47;
N, 28.95. Found C, 62.33; H, 3.43; N, 28.58%.
1-Aryl-3-(5-chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-
yl)propenones (12a,b)
A mixture of compound 4 (0.0089 mol) and aromatic
ketones (0.0178 mol) was added to 4% ethanolic potassium
hydroxide solution (50 mL). The reaction mixture was kept at
0-5 °C with stirring for 2 h; the separated product that ap-
peared was collected by filtration and recrystallized from eth-
anol.
5-Hydroxy-1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-carbo-
nitrile (9)
Yield 45%; mp 358-360 °C; IR (KBr) 3439, 2191, 1600
cm-1; 1H NMR (DMSO-d6) d 7.20-8.40 (m, 9H, Ar-H), 9.10
(s, 1H, OH). Anal. Calcd. for C15H10N4O (262.27) C, 68.69;
H, 3.48; N, 21.36. Found C, 68.26; H, 3.48; N, 21.28%.
Method B: Formation of 8
3-(5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-1-
phenylpropenone (12a)
Yield 89%; mp 126-128 °C; IR (KBr) 1658, 1620, 1610
cm-1; 1H NMR (CDCl3) d 7.00-7.70 (m, 10 H, Ar-H), 7.75 (d,
1H, CH=CH, J = 16.3 Hz), 7.90 (d, 1H, CH=CH, J = 16.3 Hz),
8.10 (d, 2H, pyridine H-3 and H-5), 8.70 (d, 2H, pyridine H-2
and H-6). Anal. Calcd. for C23H16ClN3O (385.85) C, 71.59;
H, 14.18; N, 10.89; Cl, 9.19. Found C, 71.19; H, 4.12; N,
10.53; Cl, 9.20%.
When the procedure of method A was carried out at 40
°C, 1.3 g of compound 8 was obtained as the sole product in
91% yield.
Conversion of compound 8 to compound 9
Compound 8 (0.01 mol) was dissolved in toluene (25
mL) and heated until all the starting material was consumed
(TLC). The reaction mixture was then concentrated in vacuo
and cooled. The crystalline product that appeared was col-
lected by filtration and recrystallized from ethanol to give
1.68 g of compound 9 in 64% yield.
3-(5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-1-
(4-methoxyphenyl)propenone (12b)
Yield 82%; mp 178-180 °C; IR (KBr) 1665, 1618, 1608
1
cm-1; H NMR (CDCl3) d 2.45 (s, 3H, CH3), 7.10-7.75 (m,

Synthesis of Pyrazolinone and Pyrazole Derivatives
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 989
9H, Ar-H), 7.80 (d, 1H, CH=CH, J = 16.1 Hz), 7.85 (d, 1H,
CH=CH, J = 16.1 Hz), 8.00 (d, 2H, pyridine H-3 and H-5),
8.85 (d, 2H, pyridine H-2 and H-6). Anal. Calcd. for
C24H18ClN3O (399.88) C, 72.09; H, 4.54; N, 10.51; Cl, 8.87.
Found C, 72.14; H,4.53; N, 10.15; Cl, 8.85%.
Formation of compounds 15 and 16
A mixture of compound 1 (2.8 g, 0.012 mol) in ethanol
(20 mL), compound 12b (0.01 mol) in ethanol (20 mL) and
piperidine (2 mL) was refluxed for 10 h. After cooling, the
precipitate that appeared was collected by filtration and crys-
tallized from ethanol to give 15. The mother liquor which re-
sulted after separation of compound 15 was concentrated and
upon cooling, compound 16 was separated, then collected by
filtration and recrystallized from ethanol to give 16.
Formation of compounds 13 and 14a,b
A mixture of compound 1 (2.8 g, 0.012 mol) in ethanol
(20 mL), appropriate chalcones (0.01 mol) in ethanol (20
mL), and piperidine (2 mL) was refluxed for 6 h. After cool-
ing, the precipitate that appeared was collected by filtration
and crystallized from ethanol to give 13. The mother liquors
which resulted after separation of compound 13 were concen-
trated and upon cooling, compounds 14a,b were separated,
then collected by filtration and recrystallized from ethanol/
water.
4-(5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-1,7-
diphenyl-3,5-dipyridin-4-yl-4,7-dihydro-1H-pyrano[2,3-c;
6,5-c¢]dipyrazole (15)
Yield 27%; mp 180-182 °C; IR (KBr) 2840, 1605, 1200
cm-1; 1H NMR (DMSO-d6) d 5.10 (s, 1H, pyran-H), 7.20-8.80
(m, 27H, Ar-H); MS (EI) m/z (rel. intensity) 723 (7, M+ + 1),
698 (9), 589 (10), 523 (20), 424 (32), 320 (45), 276 (40), 198
(60), 69 (100). Anal. Calcd. for C43H28ClN9O (722.21) C,
71.51; H, 3.90; N, 17.45; Cl, 4.91. Found C, 71.76; H, 3.99;
N, 17.30; Cl, 5.20%.
(4-Methoxyphenyl)-1,7-diphenyl-3,5-dipyridin-4-yl-4,7-
dihydro-1H-pyrano[2,3-c; 6,5-c¢]dipyrazole (13)
Yield 34%; mp 230-232 °C; IR (KBr) 2845, 1610, 1203
1
cm-1; H NMR (DMSO-d6) d 3.70 (s, 3H, OCH3), 5.20 (s,
3-(5-Chloro-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-3-
(5-hydroxy-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-1-(4-
methylphenyl)propan-1-one (16)
1H, pyran-H), 7.30-8.40 (m, 22H, Ar-H). Anal. Calcd. for
C36H26N6O2 (574.64) C, 75.25; H, 4.56; N, 14.62. Found C,
75.67; H, 4.90; N, 14.69%.
Yield 39%; mp 170-172 °C; IR (KBr) 3340, 1660, 1612
1
cm-1; H NMR (CDCl3) d 2.50 (s, 3H, CH3), 6.20 (d, 2H,
3-(5-Hydroxy-1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-3-
(4-ethoxyphenyl)-1-phenylpropan-1-one (14a)
CHCH2, J = 7.3 Hz), 6.70 (t, 1H, CHCH2, J = 7.3 Hz),
7.40-8.80 (m, 22H, Ar-H), 9.85 (s, 1H, OH). Anal. Calcd. for
C38H29ClN6O2 (637.14) C, 71.63; H, 4.59; N, 13.19; Cl, 5.56.
Found C, 71.50; H, 4.96; N, 13.30; Cl, 5.60%.
Yield 52%; mp 70-72 °C; IR (KBr) 3330, 1660, 1620
1
cm-1; H NMR (CDCl3) d 3.90 (s, 3H, OCH3), 6.10 (d, 2H,
CHCH2, J = 7.2 Hz), 6.60 (t, 1H, CHCH2, J = 7.2 Hz), 7.40-
8.10 (m, 18H, Ar-H), 9.80 (s, 1H, OH); MS (EI) m/z (rel. in-
tensity) 475 (2, M+), 428 (4), 368 (2), 238 (52), 223 (32), 161
(100), 105 (42), 77 (67), 51 (30). Anal. Calcd. for C30H25N3O3
(475.55) C, 75.77; H, 5.30; N, 8.84. Found C, 75.85; H, 5.11;
N, 8.72%.
Received October 20, 2003.
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(4-ethoxyphenyl)-1-(4-methoxyphenyl)propan-1-one (14b)
Yield 55%; mp 88-90 °C; IR (KBr) 3335, 1665, 1612
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