Studies on reactions of cyclic oxalyl compounds with hydrazines or hydrazones. 2. Synthesis and reactions of 4-benzoyl-1-(4-nitrophenyl)-5-phenyl- 1H-pyrazole-3-carboxylic acid

Article abstract of DOI:10.1023/B:COHC.0000046695.00178.79

4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid, obtained from the corresponding furan-2,3-dione and N-benzylidene-N'-(4- nitrophenyl)hydrazine, was converted via reactions of its acid chloride with various alcohols or N-nucleophiles in

Full text of DOI:10.1023/B:COHC.0000046695.00178.79

Chemistry of Heterocyclic Compounds, Vol. 40, No. 8, 2004
STUDIES ON REACTIONS OF CYCLIC OXALYL
COMPOUNDS WITH HYDRAZINES OR HYDRAZONES.
2*. SYNTHESIS AND REACTIONS OF 4-BENZOYL-
1-(4-NITROPHENYL)-5-PHENYL-1H-
PYRAZOLE-3-CARBOXYLIC ACID
A. Sener1, R. Kasimogullari2, M. K. Sener1, and H. Genc1
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid, obtained from the corresponding
furan-2,3-dione and N-benzylidene-N'-(4-nitrophenyl)hydrazine, was converted via reactions of its acid
chloride with various alcohols or N-nucleophiles into the corresponding ester or amide derivatives. The
nitrile of the starting acid and 1-(4-aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic acid
were also obtained. While cyclocondensation reactions of the two acids and the nitrile mentioned with
hydrazines lead to pyrazolo[3,4-d]pyridazine derivatives, the reaction of starting acid with
2-hydrazinopyridine provided the hydrazonopyrazole acid derivative.
Keywords: cyclic oxalyl compounds, pyrazole, pyrazolopyridazine, quinoline.
In the last thirty years considerable interest has been focused on pyrazole chemistry, due to the versatile
biological activities of pyrazole derivatives [2-4]. Our studies related to preparing pyrazole and fused pyrazole
derivatives by the functionalization and cyclization reactions of some pyrazolecarboxylic acids, obtained from
furandione 1, with various nucleophiles was previously reported [1, 5, 6]. In the present study, we have
attempted both to prove the reproducibility of the reaction of furandione 1 with another hydrazone and to extend
our investigations related to preparing new pyrazole derivatives.
RESULTS AND DISCUSSION
Heating of furandione 1 and benzaldehyde 4-nitrophenylhydrazone (1/1 mol) for 75 min without any
solvent led to the formation of the compound 2, in ca. 45% yield. A reasonable pathway different from that
discussed with phenylhydrazone [6] for reaction from furandione 1 to pyrazole carboxylic acid 2 is outlined
briefly in Scheme 1.
_______
* For Part 1 see [1].
__________________________________________________________________________________________
1 Yüzüncü Yil Üniversity, Art and Science Faculty, Chemistry Department, 65080 Van, Turkey; e-mail:
2
asener_2002@jahoo.com. Atatürk Üniversity, Art and Science Faculty, Chemistry Department, Erzurum,
Turkey; e-mail: rahmikasimoglu@hotmail.com Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 8,
pp. 1201-1208, August, 2004. Original article submitted August 26, 2002.
0009-3122/04/4008-1039©2004 Springer Science+Business Media, Inc.
1039

Scheme 1
_
O
O
H
COO
O
Ph
O
Ph
Ph
N(Ar)N=CHPh
_
H
+
_
N
Ph
O
Ph
O
N
H
Ar
1
A
_
O
O
COO
O
_
Ph
COO
Ph
Ph
_
OH
H
+
+
N
_
N
Ph
Ph
N
N
H
Ar
Ph
Ar
H
B
C
O
Ph
COOH
N
–PhCHO
Ph
N
Ar
2
Ar = C6H4NO2-4
Ring opening for the formation of the first intermediate A should be initiated by a nucleophilic attack of
the NH group adjacent to the phenyl ring of hydrazone at C(5) of the furandione ring similar to the reactions of
furandione 1 with various H-active nucleophiles [7, 8]. Ring closure of the intermediate A to oxadiazepine
intermediate B via addition of the N=CH–Ph group to the C=O moiety takes place by the catalytic effect of the
carboxylic acid proton similar to the addition of azines to furandiones [9]. Rearrangement of the intermediate B
generates the pyrazole carboxylate intermediate C, and finally loss of the benzaldehyde molecule gives
compound 2.
The acid 2 could be easily converted into the corresponding acid chloride 3, ester 4, amide 5, and nitrile
6 by conventional chemical procedures. Reduction of 2 with sodium polysulfide led to the derivative of
aminophenyl-substituted acid 7 (Scheme 2). The structures of the compounds thus obtained were confirmed by
analytical and spectral data (see Experimental).
The correct structures of the unsymmetrically substituted urea derivatives 5d,e were established by
another chemical procedure consisting of the reaction of the primary amide 5a with phenyl isocyanate, which
resulted in the formation of the phenylurea derivative 5d, originally prepared from the acid chloride 3 in the
usual way.
Reactions of pyrazole dicarbonyl derivatives with hydrazines are convenient methods to build the
pyrazolo[3,4-d]pyridazine systems [5, 10, 11]. Thus, the pyrazole acids 2, 7 were cyclized with hydrazines to the
pyrazolo[3,4-d]-pyridazinones 8a-d, in 40-75% yields. Additionally, 8c was also obtained by the second method
consisting of reduction of 8a with sodium polysulfide. In a similar way, pyrazole-3-carbonitrile 6 with
1040

Scheme 2
O
O
O
O
Ph
OR
Ph
COCl
Ph
COOH
ROH(Py)
SOCl2
N
N
N
Ph
Ph
Ph
N
N
N
C6H4NO2-4
C6H4NO2-4
C6H4NO2-4
3
2
4
NuH
–HCl
Na2SX
O
O
Ph
COOH
Ph
CONu
N
N
N
N
Ph
Ph
C6H4NO2-4
C6H4NH2-4
O
7
5a–e
Ph
CN
SOCl2, DMF
PhNCO
5a
N
5d
Ph
N
C6H4NO2-4
6
4 R = i-Pr; 5 a Nu = NH2, b Nu = NHEt, c Nu = NEt2, d Nu = NHCONHPh, e Nu = NHCONHBu-t
anhydrous hydrazine in boiling methanol containing a catalytic amount of sodium methoxide was also cyclized
to the 7-aminopyrazolo[3,4-d]pyridazine derivative 8e. Cyclization reactions of compounds 8c,d with
acetaldehyde in strong acidic medium lead to quinoline derivatives 9a,b (Scheme 3). Structure elucidation of
compounds 8a-e and 9a,b is based mainly on 13C NMR spectroscopy (see Experimental).
Scheme 3
R
N
N
R1
X
O
Ph
N
N
Ph
+
R1NHNH2
MeCHO(H )
N
Ph
2, 6, 7
N
N
_
(for 8c,d)
2H2O
N
Ph
N
R2
8
Me
9a,b
Na2SX
8a
8c
8a,c R1 = Ph, b, d, e R1 = H; a, b, e R2 = C6H4NO2-4, c, d R2 = C6H4NH2-4;
a-d X = O, e X = NH; 9 a R = H, b R = Ph
1041

On the other hand, the reaction of 2 with 2-hydrazinopyridine instead of phenylhydrazine or hydrazine
hydrate did not give the corresponding pyrazolopyridazine derivative. Surprisingly, however,
2-hydrazinopyridine was added to 2 to yield a new pyrazole acid 10 containing a hydrazone group. The failure
or the difficulty in forming the pyridazine nucleus from 2 with 2-hydrazinopyridine can be explained by the low
nucleophilicity of the nitrogen atom adjacent to the pyridine ring. Additionally, decarboxylation of 10 on an oil
bath at elevated temperatures led to cleavage of the C–C bond with loss of CO2, finally yielding the
corresponding hydrazonopyrazole derivative 11 (Scheme 4).
Scheme 4
C5H4N-2
N
NH
N
HN
N
COOH
Ph
Ph
2-C5H4N–NHNH2
∆
2
N
N
–CO2
Ph
Ph
N
N
C6H4NO
2 -4
C6H4NO2-4
10
11
Compounds 10 and 11 show characteristic IR absorption bands at 3450 (NH), 1681 (C=N) and 3438
(NH), 1679 cm-1 (C=N), respectively. The IR spectra of compound 10 showed no absorption bands
corresponding to the COOH group such as 3300-2500 (b, OH, COOH) and 1700-1750 cm-1 (C=O, COOH) like
that of 4-benzoyl-1,5-diphenylpyrazole-3-carboxylic acid [6]. However, absorption bands at approximately 1620
and 1579 cm-1 corresponding to an ionized carboxylate group [12] were observed. From its IR spectrum, it may
be deduced that compound 10 exists as the betaine in the solid state, but the 13C NMR signal for the carboxyl
group of 10 appears at nearly equivalent chemical shift values to that observed with carboxylic acid groups of 2
and 7. Obviously in solution the classical acid form is predominant (see Experimental).
EXPERIMENTAL
Solvents were dried by refluxing with the appropriate drying agents and distilled before use. Melting
points were determined on an Electrothermal Gallenkamp apparatus and are uncorrected. Microanalyses were
performed on a Carlo Erba Elemental Analyser Model 1108. The IR spectra were obtained in potassium
1
bromide pellets using a Mattson 1000 FTIR spectrometer. The H and 13C NMR spectra were recorded on
Varian (200 MHz) and Varian (50 MHz) spectrometers, respectively, using TMS as an internal standard. All
experiments were followed by TLC using DC Alufolien Kieselgel 60 F 254 Merck and Camag TLC lamp
(254/366 nm).
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylic Acid (2). An equimolar mixture of
furandione 1 (0.278 g, 1 mmol) and (4-nitrophenylhydrazono) (phenyl) methane (0.241 g, 1 mmol) was heated
without a solvent at 100-110°C for 75 min (up to disappearance of benzaldehyde odor). After cooling to room
temperature, the residue was treated with dry toluene and the formed crude product was recrystallized from
ethanol to give 0.186 g (45%) of a colorless solid; mp 210°C (decomp.). IR spectrum, ν, cm-1: 3400-2500 (b,
1
OH, COOH), 1717 (C=O, COOH), 1680 (C=O, benzoyl). H NMR spectrum (DMSO-d6), δ, ppm: 8.3-7.2 (m,
13
ArH). C NMR spectrum (DMSO-d6), δ, ppm: 192.26 (C=O, benzoyl); 163.83 (C=O, COOH); 148.50 (C–NO2);
1042

145.33 (C(3)); 145.22 (C(5)); 145.09 (C(1) of C6H4NO2); 139.31 (C–Ph); 135.32, 131.46, 130.90, 130.50,
130.44, 129.13 (C–Ph); 128.22, 126.34, 125.41 (C(4)). Found, %: C 66.69; H 3.69; N 10.20. C23H15N3O5.
Calculated, %: C 66.83; H 3.66; N 10.16.
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl Chloride (3). Acid 2 (0.413 g,
1 mmol) and thionyl chloride (1 ml, 13.8 mmol) were refluxed on a steam bath for 5 h. After cooling, the crude
precipitate was filtered off and recrystallized from a mixture of cyclohexane and carbon tetrachloride, yield
0.281 g (65%); mp 190°C. IR spectrum, ν, cm-1: 1757 (C=O, acyl), 1676 (C=O, benzoyl). 13C NMR spectrum
(CDCl3), δ, ppm: 190.74 (C=O, benzoyl); 162.88 (C=O, acyl); 148.69 (C–NO2); 146.47 (C(3)); 146.40 (C(5));
144.48 (C(1) of C6H4NO2); 138.30 (C–Ph); 135.26, 131.72, 130.98, 130.67, 130.49, 130.00, 127.90 (C–Ph);
127.11, 125.98, 125.72 (C(4)). Found, %: C 64.09; H 3.26; Cl 8.17; N 9.69. C23H14N3O4Cl. Calculated, %:
C 63.97; H 3.27; Cl 8.21; N 9.73.
Isopropyl 4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxylate (4). The acid chloride 3
(0.431 g, 1 mmol) and a moderate excess of isopropyl alcohol were refluxed together with a catalytic amount of
pyridine for 2.5 h. After cooling, the solution was acidified by adding diluted hydrochloric acid (12%) to give a
crude solid, which was recrystallized from the same alcohol. The yield 0.342 g (75%); mp 156°C. IR spectrum,
ν, cm-1: 1741 (C=O, ester), 1676 (C=O, benzoyl). Found, %: C 68.75; H 4.67; N 9.20. C26H21N3O5.
Calculated, %: C 68.56; H 4.65; N 9.23.
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide (5a). A moderate stream of
gaseous ammonia was allowed to bubble through a solution of acid chloride 3 (0.432 g, 1 mmol) in 20 ml of
carbon tetrachloride during 0.5 h with ice-cooling. Then the crude precipitate was filtered off and recrystallized
from methanol to give 0.289 g (70%) of 5a; mp 210°C. IR spectrum, ν, cm-1: 3438 (NH2), 1674 (C=O, benzoyl),
1625 (C=O, amide). 13C NMR spectrum (CDCl3), δ, ppm: 192.45 (C=O); 163.34 (C=O, amide); 148.17 (C–
NO2); 147.28 (C(3)); 145.49 (C(5)); 144.97 (C(1) of C6H4NO2); 139.13 (C–Ph); 134.59, 131.24, 131.01, 130.74,
130.32, 129.64, 128.78 (C–Ph); 126.68, 125.82, 124.64 (C(4)). Found, %: C 67.19; H 3.90; N 13.64.
C23H16N4O4. Calculated, %: C 66.99; H 3.91; N 13.59.
Amides 5b,c and Ureas 5d,e. (General Procedure). An equimolar mixture of the acid chloride 3 (0.431
g, 1 mmol) and the corresponding amine or urea (1 mmol) was refluxed in xylene for 3-6 h. After evaporation,
the oily residue was treated with dry ether and the formed crude product was recrystallized.
N-Ethyl-4-benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide (5b). Reflux time 3 h
(ethylamine). Yield 0.34 g (77%); mp 177°C (aqueous EtOH). IR spectrum, ν, cm-1 3259 (NH), 1676 (C=O),
1631 (C=O, amide). Found, %: C 67.99; H 4.61; N 12.68. C25H20N4O4. Calculated, %: C 68.17; H 4.58; N 12.72.
4-Benzoyl-N,N-diethyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carboxamide (5c). Reflux time
3.5 h (diethylamine). Yield 0.281 g (60%); mp 176°C (EtOH). IR spectrum, ν, cm-1: 1670 (C=O), 1632 (C=O).
Found, %: C 69.05; H 5.19; N 11.89. C27H24N4O4. Calculated, %: C 69.22; H 5.16; N 11.96.7
N-[4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl]-N'-phenylurea (5d). A. Reflux
time 4 h (phenylurea). Yield 0.186 g (35%); mp 223°C (EtOH). IR spectrum, ν, cm-1: 3405, 3320 (NH), 1745
13
(C=O, urea), 1669 (C=O), 1628 (C=O). C NMR spectrum (CDCl3), δ, ppm: 192.27 (C=O); 163.65 (C=O);
151.05 (C=O, urea); 149.98 (C–NO2); 146.17 (C(3)); 145.42 (C(1) of C6H4NO2); 145.28 (C(5)); 140.05 (N–Ph);
138.77 (C–Ph); 135.05, 132.75, 132.05, 131.88, 131.57, 131.09, 130.75, 130.43, 127.98 (C–Ph); 126.05, 125.17,
122.76, 122.35 (C(4)). Found, %: C 67.65; H 4.03; N 13.22. C30H21N5O5. Calculated, %: C 67.79; H 3.98;
N 13.18.
B. The acid amide 5a (0.412 g, 1 mmol) and phenylisocyanate (0.2 ml, 1.8 mmol) were refluxed in
xylene for 6 h. Then the solvent was evaporated and the residue was recrystallized from ethanol to give 0.425 g
(80%) of 5d, identical in mp and IR spectrum with the product obtained as described above.
N-[4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl]-N'-(tert-butyl)urea (5e). Reflux
time 4 h (tert-butylurea). Yield 0.286 g (56%); mp 244°C (n-PrOH). IR spectrum, ν, cm-1: 3380-3340 (NH),
1
1727 (C=O, urea), 1668 (C=O), 1627 (C=O). H NMR spectrum (DMSO-d6), δ, ppm: 8.9 (s, 1H, NH); 8.6 (s,
1043

1H, NH); 8.2-7.3 (m, 14H, ArH); 1.3 (s, 9H, CH3). Found, %: C 65.93; H 4.95; N 13.65. C28H25N5O5.
Calculated, %: C 65.74; H 4.93; N 13.69.
4-Benzoyl-1-(4-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonitrile (6). A cold solution of the acid
amide 5a (0.412 g, 1 mmol) in a mixture of DMF (0.7 ml) and SOCl2 (0.15 ml) was stirred at 0-5°C for 2 h.
After heating to room temperature, stirring was continued overnight, then the reaction mixture was poured onto
crushed ice and the separated solid filtered off, washed with water, and recrystallized from n-PrOH to give
0.217 g (55%) of 6 mp 214°C. IR spectrum, ν, cm-1: 2265 (CN), 1670 (C=O). 13C NMR spectrum (CDCl3),
δ, ppm: 189.01 (C=O); 148.75 (C–NO2); 146.82 (C(1) of C6H4NO2); 144.21 (C(5)); 137.80 (C(3)); 134.95,
131.77, 131.43, 130.89, 130.34, 129.72, 129.17 (C–Ph); 127.77 (C(4)); 127.15, 126.90 (C–Ph); 113.17 (CN).
Found, %: C 70.19; H 3.61; N 14.18. C23H14N4O3. Calculated, %: C 70.05; H 3.58; N 14.21.
1-(4-Aminophenyl)-4-benzoyl-5-phenyl-1H-pyrazole-3-carboxylic Acid (7). A cold solution of
sodium polysulfide (10 mmol), prepared from Na2S·9H2O (2.5 g, 10 mmol) with powdered sulfur (0.7 g) in
boiling water, was added to a solution of 2 (4.13 g, 10 mmol) in ethanol with stirring. The reaction mixture was
refluxed on a steam bath for 60 min. After cooling and acidification with concentrated HCl, it was refluxed again
for 30 min to precipitate sulfur, cooled, and the separated solid filtered off. Then, the filtrate was made alkaline
by adding concentrated aqueous ammonia (slight excess) and kept in the refrigerator overnight. The crude
precipitate was washed with water and recrystallized from a mixture of ethanol and water to give 1.96 g (51%)
of 7 mp 228°C. IR spectrum, ν, cm-1: 3438 (NH2), 3300-2500 (b, OH, COOH), 1727 (C=O, COOH), 1672
(C=O, benzoyl). 13C NMR spectrum (CDCl3), δ, ppm: 192.87 (C=O); 164.22 (COOH); 150.95 (NH2–Ph);
144.52 (C(3)); 143.42 (C(5)); 139.56 (C(1) in C6H4NH2-4); 135.10, 131.37, 130.80, 130.71 (C–Ph); 130.41,
130.10, 129.94, 128.92 (C–Ph); 128.58, 123.99, 115.08 (C(4)). Found, %: C 72.25; H 4.45; N 10.93.
C23H17N3O3. Calculated, %: C 72.05; H 4.47; N 10.96.
2,6-Dihydropyrazolo[3,4-d]pyridazin-7-ones 8a-d. (General Procedure). An equimolar mixture of 2
and the respective hydrazine was refluxed in xylene for 1-4 h. After the solvent was removed by evaporation, the
oily residue was treated with ether and the formed crude product was recrystallized.
2-(4-Nitrophenyl)-3,4,6-triphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (8a). Reflux time 3 h
(phenylhydrazine). Yield 0.364 g (75%); mp 267°C (methanol). IR spectrum, ν, cm-1: 1686 (C=O). 13C NMR
spectrum (DMSO-d6), δ, ppm: 156.60 (C=O); 148.68 (C–NO2); 145.48 (C(7a)); 145.17 (C(4)); 145.035 (C(3));
142.96 (C(1) in C6H4NO2); 141.87 (C(1) in N–Ph); 135.14, 131.66, 131.07 (C–Ph); 130.03, 129.97, 129.89,
129.03, 128.92, 128.71 (C–Ph); 127.87, 127.26, 125.67, 118.59 (C(3a)). Found, %: C 71.55; H 3.97; N 14.38.
C29H19N5O3. Calculated, %: C 71.74; H 3.94; N 14.42.
2-(4-Nitrophenyl)-3,4-diphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (8b). Reflux time 1 h
-1
→
(hydrazine hydrate). Yield 0.299 g (73%); mp 305°C (n-BuOH). IR spectrum, ν, cm : 3300-2800 (b, NH OH),
←
1677 (C=O). 13C NMR spectrum (DMSO-d6), δ, ppm: 157.74 (C=O); 148.90 (C–NO2); 145.37 (C(7a)); 144.43
(C(4)); 142.51 (C(3)); 141.19 (C(1) in C6H4NO2), 135.88, 132.38, 131.09, 130.06, 129.99 (C–Ph); 129.81,
129.23, 129.14, 129.05 (C–Ph); 126.17, 118.76 (C(3a)). Found, %: C 67.31; H 3.71; N, 17.17. C23H15N5O3.
Calcula-ted, %: C 67.48; H 3.69; N 17.11.
2-(4-Aminophenyl)-3,4,6-triphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (8c). A. Reflux time
4 h (phenylhydrazine). Yield 0.205 g (45%); mp 290°C (n-BuOH). IR spectrum, ν, cm-1: 3489-3387 (NH2), 1667
1
(C=O). H NMR spectrum (CDCl3), δ, ppm: 7.6-6.6 (m, 19H, ArH); 3.9-2.6 (b, 2H, NH2). 13C NMR spectrum
(CDCl3), δ, ppm: 157.77 (C=O); 148.99 (C–NH2); 146.23 (C(7a)); 144.87 (C(4)); 143.93 (C(3)); 141.69 (C(1) in
N–Ph); 136.25 (C(1) in C6H4NH2); 132.53, 131.92 (C–Ph); 130.80, 130.66, 130.46, 130.23 (C–Ph); 130.04,
129.61, 129.42, 129.10, 128.11, 118.40 (C(3a)); 116.72. Found, %: C 76.75; H 4.66; N 15.41. C29H21N5O.
Calculated, %: C 76.47; H 4.65; N 15.37.
B. Pyridazinone 8a (0.485 g, 1 mmol) and Na2SX (1 mmol) were refluxed in a mixture of EtOH and
water on a steam bath for about 1 h. The crude product which precipitated in boiling solvents was filtered off and
recrystallized from n-BuOH to give 0.273 g (60%) of 8c, identical in mp and IR spectrum with the product
obtained as described above.
1044

2-(4-Aminophenyl)-3,4-diphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (8d). Reflux time 3 h
(hydrazine hydrate). Yield 0.152 g (40 %); mp 342°C (EtOH). IR spectrum, ν, cm-1: 3489-3308 (NH2),
3250-2800 (b, NH OH), 1659 (C=O). 13C NMR spectrum (DMSO-d6), δ, ppm: 157.98 (C=O); 151.17 (C–
→
←
NH2); 145.37 (C(7a)); 143.18 (C(4)); 141.54 (C(3)); 136.19 (C(1) in C6H4NH2); 132.35, 130.37 (C–Ph); 130.06,
129.83, 129.75, 129.42, 129.08, 128.97 (C–Ph); 128.79, 118.01 (C(3a)); 114.86. Found, %: C 72.99; H 4.54; N
18.41. C23H17N5O. Calculated, %: C 72.81; H 4.52; N 18.46.
[2-(4-Nitrophenyl)-3,4-diphenyl-2H-pyrazolo[3,4-d]pyridazin-7-yl]amine (8e). Nitrile 6 (0.394 g,
1 mmol) and anhydrous hydrazine (0.032 g, 1 mmol) were refluxed in methanol containing a catalytic amount of
sodium methoxide on an oil bath for 15 h. After cooling to room temperature, the crude precipitate was isolated
by filtration and recrystallized from n-BuOH. Yield 0.225 g (55%); mp 315°C. IR spectrum, ν, cm-1: 3300-3000
(NH), 1663 (C=NH). 13C NMR spectrum (CDCl3), δ, ppm: 158.05 (C=NH); 149.11 (C–NO2); 146.77 (C(1) in
C6H4NO2); 146.40 (C(7a)); 144.31 (C(3)); 140.88 (C(4)); 133.07, 132.03 (C–Ph); 131.99, 131.04 (C–Ph);
130.71, 130.23, 129.59, 129.17, 128.75, 127.25, 123.28 (C(3a)). Found, %: C 67.58; H 4.02; N 20.51.
C23H16N6O2. Calculated, %: C 67.64; H 3.95; N 20.58.
2-(2-Methylquinolin-6-yl)-3,4-diphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (9a). To a cold
solution of compound 8d (1 mmol) in concentrated HCl (15-20 ml), acetaldehyde (0.1 ml, 2 mmol) and
nitrobenzene (0.123 g, 1 mmol) were added with stirring, and stirring was continued at room temperature for 2 h.
Then, the reaction mixture was refluxed on a steam bath for 10 h with stirring and filtered. The filtrate was made
alkaline by adding concentrated aqueous ammonia and kept in a refrigerator overnight. The separated solid was
filtered off, washed with water, and recrystallized from a mixture of methanol and water. Yield 0.193 g (45%);
-1
13
→
mp 280°C. IR spectrum, ν, cm : 3450-2750 (NH OH), 1663 (C=O). C NMR spectrum (DMSO-d ), δ, ppm:
←
6
162.36 (C=O); 157.95 (C(2')); 148.26 (C(8'a)); 145.37 (C(7a)); 143.99 (C(4)); 142.29 (C(3)); 138.20, 137.54,
136.04, 132.33, 130.72, 130.48 (C–Ph); 130.08, 129.81 (C–Ph); 129.58, 129.42, 129.15, 128.91, 128.76, 127.34,
125.03, 118.40 (C(3a)); 26.69 (Me). Found, %: C 75.30; H 4.48; N 16.27. C27H19N5O. Calculated, %: C 75.51;
H 4.46; N 16.31.
2-(2-Methylquinolin-6-yl)-3,4,6-triphenyl-2,6-dihydropyrazolo[3,4-d]pyridazin-7-one (9b) was
obtained similarly to 9a from 8c. Reflux time 8 h, yield 0.237 g (46%); mp 244°C (methanol). IR spectrum,
ν, cm-1: 1666 (C=O). 13C NMR spectrum (DMSO-d6), δ, ppm: 162.48 (C=O); 156.59 (C(2')); 148.35 (C(8'a));
145.60 (C(7a)); 144.18 (C(4)); 143.46 (C(3)); 142.80, 138.26, 137.47, 135.51, 132.41, 130.93, 130.83, 130.48
(C–Ph); 130.39, 130.23, 129.69, 129.32, 129.21, 128.91 (C–Ph); 128.11, 127.40, 127.27, 125.12, 118.14
(C(3a)); 26.71 (Me). Found, %: C 78.17; H 4.54; N 13.82. C33H23N5O. Calculated, %: C 78.41; H 4.55; N 13.86.
1-(4-Nitrophenyl)-5-phenyl-4-[phenyl(pyridin-2-ylhydrazono)methyl]-1H-pyrazole-3-carboxylic
Acid (10). Compound 2 (0.413 g, 1 mmol) and 0.109 g (1 mmol) of 2-hydrazinopyridine were refluxed in xylene
on an oil bath for 3 h. The solvent was evaporated and the remaining oily residue was treated with ether to give a
crude product which was recrystallized from ethanol. Yield 0.434 g (86%); mp 309°C (decomp.). IR spectrum,
1
ν, cm-1: 3450 (NH), 1681 (C=N–), 1620, 1579 (COO-). H NMR spectrum (DMSO-d6), δ, ppm: 10.1 (b, acidic
proton); 8.9 (b, 1H, NH); 8.3-6.8 (m, 18H, ArH). 13C NMR spectrum (DMSO-d6),δ, ppm: 163.99 (COO-);
156.82 (C(2'), Py); 149.25 (C–NO2); 148.22 (C=N–); 145.88 (C(3)); 145.82 (C(6'), Py); 144.97 (C(5)); 139.84
(C(1) in C6H4NO2); 139.76, 138.81, 131.16, 131.08 (C–Ph); 130.83, 130.43, 129.93, 129.61 (C–Ph); 128.08,
127.36, 126.20, 126.10, 117.37, 109.08 (C(4)). Found, %: C 66.51; H 4.05; N 16.73. C28H20N6O4. Calculated, %:
C 66.66; H 4.00; N 16.66.
[1-(4-Nitrophenyl)-5-phenyl-1H-pyrazol-4-yl(phenyl)methanone-N-pyridin-2-ylhydrazone
(11).
Compound 10 (0.46 g, 1 mmol) was heated to 310-315°C on an oil bath for about 0.5 h without a solvent. After
cooling to room temperature, the residue was treated with ether to give a crude product which was recrystallized
from ethanol. Yield 0.253 g (55%); mp 320°C. IR spectrum, ν, cm-1: 3438 (NH), 1679 (C=N–). 13C NMR
spectrum (CDCl3), δ, ppm: 156.65 (C(2'), Py); 155.22 (C=N–); 150.84 (C(6'), Py); 149.09 (C–NO2); 145.51
1045

(C(3)); 145.24 (C(5)); 144.47 (C(1) in C6H4NO2); 143.24 (C–Ph); 140.46, 135.18, 132.37, 131.28, 130.39,
129.89, 129.32, 129.24, 128.70 (C–Ph); 126.77, 125.83, 124.08, 118.70 (C(4)). Found, %: C 70.53; H 4.39;
N 18.20. C27H20N6O2. Calculated, %: C 70.42; H 4.38; N 18.25.
The authors thank the research fund of Y. Yil University for financial support.
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