Synthesis and characterization of some pyrazole derivatives of 1,5-diphenyl-1H-pyrazole-3,4-dicarboxylic acid

Article abstract of DOI:10.1002/jhet.416

(Chemical Equation Presented) Compound of 4-(ethoxycarbonyl)-1,5-diphenyl- 1H-pyrazole-3-carboxylic acid 2 was obtained from the reaction of ethyl 4,5-dioxo-2-phenyl-4,5-dihydrofuran-3-carboxylate and 1-benzylidene-2- phenylhydrazine. A number of substitute pyrazole dicarboxylic acid derivatives (4, 5a-c, 6, 7, 8, 9a-m, 10, 11, 12, 13, 14) were synthesized from 1,5-diphenyl-1H-pyrazole-3,4-dicarboxylic acid 3 which was prepared from basic hydrolysis of 2. Structures of synthesized compounds were characterized by ¹H NMR, ¹³C NMR, Mass, FTIR, and elemental analysis.

Full text of DOI:10.1002/jhet.416

1040
Synthesis and Characterization of Some Pyrazole Derivatives of
1,5-Diphenyl-1H-pyrazole-3,4-dicarboxylic Acid
Vol 47
˘
Rahmi Kasımogulları* and B. Sec¸kin Arslan
Department of Chemistry, Faculty of Arts and Sciences, Dumlupinar University,
Kutahya 43100, Turkey
*E-mail: rahmikasimoglu@hotmail.com
Received September 9, 2009
DOI 10.1002/jhet.416
Published online 13 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
Compound of 4-(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carboxylic acid 2 was obtained from
the reaction of ethyl 4,5-dioxo-2-phenyl-4,5-dihydrofuran-3-carboxylate and 1-benzylidene-2-phenylhy-
drazine. A number of substitute pyrazole dicarboxylic acid derivatives (4, 5a–c, 6, 7, 8, 9a–m, 10, 11,
12, 13, 14) were synthesized from 1,5-diphenyl-1H-pyrazole-3,4-dicarboxylic acid 3 which was prepared
1
from basic hydrolysis of 2. Structures of synthesized compounds were characterized by H NMR, 13C
NMR, Mass, FTIR, and elemental analysis.
J. Heterocyclic Chem., 47, 1040 (2010).
INTRODUCTION
of 1,5-diphenyl-1H-pyrazole-3,4-dicarboxylic acids
although a number of new derivatives of pyrazoles some
of which have bicyclic structure were synthesized [26–
29]. In this research, we decided to extend our previous
studies to satisfy this deficiency and to synthesize differ-
ent derivatives of pyrazole compounds that show biologi-
cal activity [20,21,26,29].
The chemistry of pyrazole derivatives have been the
subject of much research because of their importance in
various applications and their widespread potential bio-
logical and pharmacological activities such as antimicro-
bial, antiviral, antitumor, anti-inflammatory, pesticidal,
antifungal, antidepressant, antipyretic, and analgesic [1–
10]. Thus, these compounds have been the focus of high
attention among medicinal chemists [11–16]. It is also
known that biological activities of pyrazole derivatives
which include substituted heteroaryl groups increase and
that some pyrazolo-pyridazine compounds which include
the same heteroaryl groups are used as a cure for many
diseases [17–25].
RESULTS AND DISCUSSION
1,5-Diphenyl-1H-pyrazole-3,4-dicarboxylic acid 3,
which was our initial compound, was prepared after var-
ious reaction steps. First, ethyl 4,5-dioxo–2-phenyl-4,5–
dihydrofuran–3-carboxylate 1 compound was prepared
from the reactions of ethyl 3-oxo-3-phenylpropanoate
and oxalyl dichloride [32,33]. Keeping in mind that H-
active nucleophiles attack the C-2, C-3, and C-4 posi-
tions of furandiones and it starts the reactions in which
intermediate products were formed, NH group attacks to
Pyrazole-3-carboxylic acid derivatives in general are
well-known nitrogen-containing heterocyclic com-
pounds, and various procedures have been developed for
their syntheses [26–31]. In the literature, there is
not much research related to the reactions of derivatives
C
V
2010 HeteroCorporation

September 2010 Synthesis and Characterization of Some Pyrazole Derivatives of 1,5-Diphenyl-
1H-pyrazole-3,4-dicarboxylic Acid
1041
Scheme 1
C-3 and C-4 positions of furandione in the condensation
reaction of 1 with 1-benzylidene-2-phenylhydrazine in
no solvent media [26,27,30]. The possible reaction steps
of 4-(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-car-
boxylic acid 2 was given in Scheme 1.
Diester derivatives of Compound 3 were obtained in
two different methods. In the first method, carboxylic
groups of 3 were activated with SOCl2 and gave the 4.
Afterward, the diester derivatives 5a–c were obtained
from the reaction of 4 with various alcohols with pyri-
dine catalyst. However, it was understood from TLC
works that synthesized products by this method con-
tained impurity. This impurity was probably resulted
from pyridine and was difficult to remove. In the second
method, compound 3 gave the purer diester products
5a–c about in yield of 61–75%. For this reason, the
compound 3 was heated with various alcohols in ben-
zene with sulfuric acid catalyst (Scheme 2). The second
method was chosen in this study. On the other hand,
heating the compound 4 in dry benzene with AlCl3
1,5-Diphenyl-1H-pyrazole-3,4-dicarboxylic acid
3
compound was prepared from the basic hydrolysis of 2
at a high yield (92%). The long reaction time increased
the yield. The structure was confirmed with the charac-
teristic IR absorption bands at 3354–2454 cmꢀ1
(COOH), 3064 cmꢀ1 (Ar CH ), 1670 cmꢀ1 (acid,
C¼¼O), 1597–1486 cmꢀ1 (C¼¼C and C¼¼N) and the 13C
NMR signals at d ¼ 163.75 and d ¼ 164.61 (acid,
C¼¼O). 306 m/z (M-2) value in mass spectra for 3
showed the existence of molecular ion structure.
Scheme 2
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DOI 10.1002/jhet

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R. Kasımogulları and B. Sec¸kin Arslan
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Vol 47
Scheme 3
catalyst [34] gave 1-phenyl-1H-pyrazole-3,4-diyl)
bis(phenylmethanone 6 (Scheme 2).
yield [20,26]. Compound 10 showed characteristic IR
absorption band at 2231 cmꢀ1 (CBN). IR spectra of
compound 10 showed no absorption bands correspond-
ing to the COOH group such as 3300–2500 cmꢀ1
(COOH) and 1700–1750 cmꢀ1 (acid, C¼¼O) like the
1,5-diphenyl-1H-pyrazole-3,4-dicarboxylic acid. Further-
more, 13C NMR signals at d ¼ 110.77–110.80 ppm
were related to carbon of nitrile (CBN).
NH2 groups of hydrazine which have strong nucleo-
philic property attacks to benzoyl carbons when the
compound 6 was heated with anhydrous hydrazine. In
the second stage, cyclization occurred with the removal
of two moles water, and pyrazolo-pyridazine derivative
7 was obtained (Scheme 2).
Moreover, heating of 3 in acetic anhydride caused the
leaving of one mole water. As a result of this, furo[3,4-c]
pyrazole-4,6-dione 8 (Scheme 2) was synthesized [35–
37]. However, it was also observed from TLC controls
that this compound was very sensitive to oxidation in air
and returned to its initial compound. Therefore, it is suita-
ble to handle this compound in desiccator by being dried
with P2O5.
Reaction of 10 with anhydrous hydrazine in absolute
ethanol led to the formation of the 2,3-diphenyl-2H-pyr-
azolo[3,4-d]pyridazine-4,7-diamine 11 in about 69%
yield (Scheme 4). Structure of the compound was con-
firmed with spectral data (See Experiments).
Scheme 4
Derivatives of pyrazole-3,4-dicarboxamide 9a–m
were prepared easily by reaction of 4 with ammonia,
substituted aryl amines, and a series of alkyl amines
(Scheme 3). Structures of the compounds were con-
firmed with spectral data.
As a result of dehydration of 9a in cold DMF and
SOCl2 mix, dinitrile 10 compound occurred at 96%
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September 2010 Synthesis and Characterization of Some Pyrazole Derivatives of 1,5-Diphenyl-
1H-pyrazole-3,4-dicarboxylic Acid
1043
1
FTIR with using of KBr pellets. H NMR and 13C NMR
spectra were evaluated by BRUKER DPX-400,
(400MHz), and High Performance Digital FT-NMR
(100MHz) spectrometers. Mass spectra data were deter-
mined by Varian Mat III 80 eV. Elemental analyses
were carried out on a Leco CHNS-932 instrument.
Scheme 5
1,5-Diphenyl-1H-pyrazole-3,4-dicarboxylic acid
(3). Compound 2 of 0.336 g (1 mmol) was refluxed in
solution of 0.1 g (2.5 mmol) NaOH for about 1.5 h.
Mixed solution was cooled down to room temperature.
It was stirred for a while by adding 1.5 mL concentrated
HCl and water at equal volume. Precipitated white solid
product was filtered and washed with water again. It
was purified from water–ethanol mixture by crystalliza-
tion. (283 mg, 92%); mp 224–225ꢁC; IR (m, cmꢀ1):
3354–2454 (OH, COOH), 3064 (CH, aromatic), 1670
As a result of decarboxylation of 2 at high tempera-
ture (200–220ꢁC), the compound 12 was obtained and
the compound 13 was synthesized after basic hydrolysis
of 12. It was understood from TLC and spectral data
that basic hydrolysis of 12 and decarboxylation of 3
gave the same products 1,5-diphenyl-1H-pyrazole-4-car-
boxylic acid 13. After decarboxylation of 3, it was
shown that leaving carboxyl group bonded the adjacent
carbon to nitrogen (Scheme 5).
1
(C¼¼O), 1597–1486 (C¼¼C and C¼¼N); H NMR (400
MHz, CDCl3) d (ppm): 7.27–7.40 (m, 10H, ArH); 13C
NMR (100 MHz, CDCl3) d (ppm): 164.61 and 163.76
(C¼¼O, acid), 144.85 (C–3), 144.31(C–5), 116.14 (C–4),
138.93, 130.53, 129.74, 129.52, 129.21, 128.67, 128.54,
126.32; MS(CI) m/z 306.0 (M–2, COOꢀ); Anal. Calcd.
for C17H12N2O4: C, 66.23; H, 3.92; N, 9.09. Found: C,
66.56; H, 3.65; N, 9.12.
On the other hand, cyclo-condensation reaction of 2
and 5a with hydrazine hydrate gave the same product
pyrazolo[3,4-d]pyridazine-4,7-dione 14 [6,26]. IR, 1H
NMR, and 13C NMR spectra [IR: 3158–2629), 1H
NMR: 10.40 (br. s, 1H, NHAC¼¼O), 5.30 (br. s, 1H,
N¼¼CAOH), 13C NMR: 161.79 and 161.58 (C¼¼O, C-
4), 156.58 and 152.33 (C¼¼O, C-7)] showed evidence
1,5-Diphenyl-1H-pyrazole-3,4-dicarbonyl dichloride
(4). Compound 3 of 0.308 g (1 mmol) was refluxed
with excessive SOCl2 at 80ꢁC for about 5 h. Excessive
SOCl2 was evaporated. Remaining oily product was
purified in ether–hexane mixture. (259 mg, 75%); mp
86–89ꢁC; IR (m, cmꢀ1): 3060 (CH, aromatic), 1735
1
(C¼¼O), 1620–1487 (C¼¼C and C¼¼N); H NMR (400
MHz, CDCl3) d (ppm): 7.00–7.72 (m, 10H, ArH); 13C
NMR (100 MHz, CDCl3) d (ppm): 161.39 and 161.09
(C¼¼O), 146.54 (C–3), 143.96 (C–5), 120.35 (C-4),
137.82, 130.60, 130.09, 129.56, 129.35, 128.90,
126.13, 125.51; Anal. Calcd. for C17H10Cl2N2O2: C,
59.15; H, 2.92; N, 8.12. Found: C, 59.35; H, 2.79; N,
8.10.
of the presence of
a
tautomeric equilibrium
(HNAC¼¼O$N¼¼CAOH) between the two tautomers
(keto-enol) of compound 14 (Scheme 6).
In this research, a number of derivatives of substituted
pyrazole dicarboxylic acids were gained to pyrazole
chemistry and characterization of each compound were
performed with the help of spectral data (See
Experiments).
General procedure for compounds 5a–c. Compound
3 of 1 mmol was dissolved in 10 mL dry benzene, and
2 mL alcohol (MeOH, i-PrOH, BuOH) and 0.2 mL
H2SO4 was added to this solution. Mixture was refluxed
for 4–5 h. After evaporation, some water was added to
the product remaining at the bottom of the flask and
transferred to separate funnel. 10 mL of ether was added
EXPERIMENTS
The optimum reaction conditions were determined
considering the time, concentration, solvent, and struc-
ture of reactive compounds which were effective on
yield and velocity of chemical reactions. Chemical com-
pounds used in this research were at analytical purity,
and the solvents were purified by using appropriate puri-
fying agents and distillation. At the end of the each
experiment, TLC was performed using DC Alufolien
Kiesegel 60F/254 Merck and Camag TLC devices. Melt-
ing points were measured with Barnstead Electrothermal
9200 apparatus and were not corrected. IR spectrum
data of compounds were determined by Mattson 1000
Scheme 6
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DOI 10.1002/jhet

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R. Kasımogulları and B. Sec¸kin Arslan
1044
Vol 47
1
to the mixture and was washed with 10% Na2CO3 solu-
tion. Ether was evaporated after separation of organic
phase. The synthesized crude products 5a–c were puri-
fied from hexane.
1664 (C¼¼O), 1617–1489 (C¼¼C and C¼¼N); H NMR
(400 MHz, DMSO-d6) d (ppm): 8.20–7.23 (m, 20H,
ArH); 13C NMR (100 MHz, DMSO-d6) d (ppm): 191.04
and 187.16 (C¼¼O, benzoyl), 149.43 (C–3), 144.01
(C–5), 123.85 (C–4), 139.04, 137.98, 136.47, 134.01,
133.80, 130.72, 130.70, 130.29, 129.82, 129.64, 129.39,
129.05, 129.02, 128.90, 128.07, 126.48; Anal. Calcd. for
C29H20N2O2: C, 81.29; H, 4.70; N, 6.54. Found: C,
81.42; H, 4.65; N, 6.51
Dimethyl-1,5-diphenyl-1H-pyrazole-3,4-dicarboxylate (5a). (205
mg, 61%); mp 96–97ꢁC; IR (m, cmꢀ1): 3002 (CH, aro-
matic), 2952 (CH, aliphatic), 1718 (C¼¼O), 1596–1497
(C¼¼C and C¼¼N); 1H NMR (400 MHz, CDCl3) d
(ppm): 7.39–7.23 (m, 10H, ArH), 4.00 and 3.78 (s, 6H,
2OCH3); 13C NMR (100 MHz, CDCl3) d (ppm): 163.48
and 162.31 (C¼¼O), 144.86 (C–3), 143.21 (C–5), 115.56
(C–4), 52.63 and 52.25 (2OCH3), 138.62, 130.05,
129.53, 128.99, 128.63, 128.38, 127.82, 125.63; Anal.
Calcd. for C19H16N2O4: C, 67.85; H, 4.79; N, 8.33.
2,3,4,7-Tetraphenyl-2H-pyrazolo[3,4-d]pyridazine
(7). Compound 6 of 1 mmol was dissolved in dry xy-
lene, and 0.1 mL hydrazine was added and refluxed for
4 h. Then, solvent was evaporated and 10 mL ether was
added to residue product and stirred for a while in cold.
Precipitated yellow product was filtered, washed with
water, and purified from ethanol–water mixture by crys-
tallization. (343 mg, 81%); mp 194–196ꢁC; IR (m,
cmꢀ1): 3057 and 3030 (CH, aromatic), 1590–1488
Found: C, 67.68; H, 4.89; N, 8.32.
Diisopropyl-1,5-diphenyl-1H-pyrazole-3,4-dicarboxylate
(5b). (239 mg, 61%); mp 96–97ꢁC; IR (m, cmꢀ1): 3059
(CH, aromatic), 2937 (CH, aliphatic), 1710 (C¼¼O),
1599–1498 (C¼¼C and C¼¼N); 1H NMR (400 MHz,
CDCl3) d (ppm): 7.39–7.24 (m, 10H, ArH), 5.36 and
5.12 (p, J ¼ 6.3 Hz, 2H, 2OCH), 1.45 and 1.27 (d, J ¼
6.3 Hz, 12H, 2CH(CH3)2); 13C NMR (100 MHz,
CDCl3) d (ppm): 162.51 and 161.80 (C¼¼O), 144.41 (C–
3), 144.09 (C–2), 115.93 (C–4), 69.54 and 68.73 (OCH),
21.83 and 21.57 (CH3), 138.73, 130.11, 129.32, 128.92,
128.44, 128.24, 128.22, 125.63; Anal. Calcd. for
C23H24N2O4: C, 70.39; H, 6.16; N, 7.14. Found: C,
70.25; H, 6.19; N, 7.21.
1
(C¼¼C and C¼¼N); H NMR (400 MHz, DMSO-d6) d
(ppm): 7.57–7.01 (m, 20H, ArH); 13C NMR (100 MHz,
DMSO-d6) d (ppm): 156.57 and 149.93 (C–4 and C–7),
141.89, 139.85, 139.51, 137.01, 135.72, 135.35, 131.21,
130.80, 130.03, 129.53, 129.47, 129.41, 129.35, 129.13,
128.50, 128.32, 127.84, 127.28, 116.17 Anal. Calcd. for
C29H20N4: C, 82.05; H, 4.75; N, 13.20. Found: C,
81.93; H, 4.67; N, 13.28.
2,3-Diphenyl-2H-furo[3,4-c]pyrazole-4,6-dione
(8). Compound 3 of 0.308 g (1 mmol) was transferred
to a flask. 2.5 mL acetic anhydride and 0.1 mL pyridine
was added and refluxed for about 4 h. Excessive amount
of solvent was evaporated. The residue product was
purified from hexane and chloroform mixture by crystal-
lization. (226 mg, 78%); mp 176–178ꢁC; IR (m, cmꢀ1):
3072 (CH, aromatic), 1810 and 1708 (C¼¼O), 1628–
Dibutyl
1,5-diphenyl-1H-pyrazole-3,4-dicarboxylate
(5c). (286 mg, 68%); mp 49–50ꢁC; IR (m, cmꢀ1): 3062
(CH, aromatic), 2959 (CH, aliphatic), 1719 (C¼¼O),
1596–1498 (C¼¼C and C¼¼N); 1H NMR (400 MHz,
CDCl3) d (ppm): 7.38–7.23 (m, 10H, ArH), 4.42 and
4.18 (t, J ¼ 6.8 Hz, 4H, 2OCH2), 1.81 (p, J ¼ 7.2 Hz,
4H, 2OCH2CH2CH2), 1.62–1.46 (m, 4H, CH2CH2CH3
1
1489 (C¼¼C and C¼¼N); H NMR (400 MHz, DMSO-
d6) d (ppm): 7.30–7.01 (m, 10H, ArH); 13C NMR (100
MHz, DMSO-d6) d (ppm): 164.46 and 164.15 (C¼¼O),
146.99, 140.71, 139.12, 130.77, 129.41, 129.23, 129.03,
128.43, 126.33, 125.74, 116.25; MS(CI) m/z 291.0
(Mþ1); Anal. Calcd. for C17H10N2O3: C, 70.34; H,
3.47; N, 9.65. Found: C, 70.48; H, 3.35; N, 9.72.
and OCH2CH2CH2), 1.21 (h,
J
¼
7.5 Hz, 2H,
CH2CH2CH3), 0.99 and 0.86 (t, J ¼ 7.4 Hz, 6H, 2CH3);
13C NMR (100 MHz, CDCl3) d (ppm): 163.03 and
162.31 (C¼¼O), 144.64 (C–3), 143.94 (C–5), 115.49 (C–
4), 65.60 and 64.99 (OCH2), 30.65 and 30.41
(CH2CH2CH2), 19.11 and 18.97 (CH2CH2CH3), 13.75
and 13.64 (CH3), 138.66, 130.10, 129.39, 128.92,
128.48, 128.31, 128.14, 125.58, 118.80; Anal. Calcd. for
C25H28N2O4: C, 71.41; H, 6.71; N, 6.66. Found: C,
71.29; H, 6.79; N, 6.65.
1,5-Diphenyl-1H-pyrazole-3,4-dicarboxamide
(9a). Compound 4 of 0.345 g (1 mmol) was dissolved
in CCl4 and cooled down to 0ꢁC. Excessive amount of
NH3 was added to this solution. To complete the reac-
tion, mixture was stirred for about an hour at room tem-
perature. Precipitated white product was washed with
water and purified from ethanol by crystallization.
(217 mg, 71%); mp 286–287ꢁC; IR (m, cmꢀ1): 3308
and 3146 (NH), 3073 (CH, aromatic), 1650 (amide
C¼¼O), 1587–1489 (C¼¼C and C¼¼N); 1H NMR (400
MHz, DMSO-d6) d (ppm): 8.06 and 7.76 (br. 4H, 2NH2),
7.39–7.24 (m, 10H, ArH); 13C NMR (100 MHz, DMSO-
d6) d (ppm): 165.10 and 161.30 (C¼¼O), 143.60 (C–3),
(1,5-Diphenyl-1H-pyrazole-3,4-diyl)bis (phenylme-
thanone) (6). Compound 4 of 0.345 g (1 mmol) was
dissolved in dry benzene, and 0.33 g (2.5 mmol) AlCl3
was added to this solution. After cooling down of mix-
ture which was refluxed for 3 h, organic phase was sep-
arated by adding some ether and ice water. Then ether
was evaporated and the residue solid was recrystallized
from ethanol–water mixture. (253 mg, 59%); mp 174–
175ꢁC; IR (m, cmꢀ1): 3064 and 3028 (CH, aromatic),
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September 2010 Synthesis and Characterization of Some Pyrazole Derivatives of 1,5-Diphenyl-
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1045
1,5-Diphenyl-N3,N4-dibutyl-1H-pyrazole-3,4-dicarboxamide
139.56 (C–5), 119.80 (C–4), 130.15, 129.81, 129.55,
129.12, 128.40, 128.31, 128.13, 123.50; MS(CI) m/z
307.1 (Mþ1); Anal. Calcd. for C17H14N4O2: C, 66.66; H,
4.61; N, 18.29. Found: C, 66.61; H, 4.69; N, 18.27.
(9e). (334 mg, 80%); mp 133–134ꢁC; (was crystallized
from ether/hexane); IR (m, cmꢀ1): 3371 and 3256 (NH),
3033 (CH, aromatic), 2960, 2931 and 2871 (CH, ali-
1
phatic), 1657 (C¼¼O), 1627–1493 (C¼¼C and C¼¼N); H
General procedure for compounds 9b–m. Compound
4 of 0.345 g (1 mmol) was dissolved in 10 mL dry xy-
lene and 4 mmol aryl or alkyl amine compound was
added. Mixture was refluxed for 3 h and solvent was
evaporated. The crude product was washed with water
NMR (400 MHz, CDCl3) d (ppm): 10.34 and 7.51 (m,
2H, 2NH), 7.33–7.17 (m, 10H, ArH), 3.50 and 3.36 (q,
J ¼ 7.1 Hz, 4H, 2NHCH2CH2), 1.65–1.59 (m, 4H,
2CH2CH2CH2), 1.54–1.22 (m, 4H, 2CH2CH3), 1.11–
0.78 (m, 6H, 2CH3); 13C NMR (100 MHz, CDCl3) d
(ppm): 163.23 and 161.45 (C¼¼O), 148.30 (C–3), 142.68
(C–5), 117.34 (C–4), 39.35 and 39.19 (NHCH2), 31.55
(CH2CH2CH2), 20.37 and 20.16 (CH2CH3), 13.89 and
13.32 (CH3), 138.79, 130.54, 129.88, 128.84, 128.40,
128.38, 127.95, 125.61; Anal. Calcd. for C25H30N4O2:
C, 71.74; H, 7.22; N, 13.39. Found: C, 71.59; H, 7.28;
and purified from an appropriate solvent.
1,5-Diphenyl-N3,N4-diethyl-1H-pyrazole-3,4-dicarboxamide
(9b). (304 mg, 84%); mp 138–139ꢁC; (was crystallized
from EtOH/H2O); IR (m, cmꢀ1): 3456 and 3291 (NH),
3077 (CH, aromatic), 2974 and 2930 (CH, aliphatic),
1
1644 (C¼¼O), 1553–1496 (C¼¼C and C¼¼N); H NMR
(400 MHz, CDCl3) d (ppm): 10.35 (m, 2H, 2NH), 7.35–
7.17 (m, 10H, ArH), 3.52 and 3.40 (p, J ¼ 3.6 Hz, 4H,
2CH2), 1.32 and 1.21 (t, J ¼ 7.3 Hz, 6H, 2CH3); 13C
NMR (100 MHz, CDCl3) d (ppm): 163.15 and 161.36
(C¼¼O), 148.38 (C–3), 142.56 (C–5), 117.34 (C–4),
34.49 and 34.08 (NHCH2), 14.72 and 14.67 (CH3),
138.78, 130.53, 129.85, 129.75, 128.85, 128.43, 127.95,
125.62; Anal. Calcd. for C21H22N4O2: C, 69.59; H,
N, 13.45.
1,5-Diphenyl-N3,N4-di-tert-butyl-1H-pyrazole-3,4-dicarbox-
amide (9f). (343 mg, 82%); mp 174–175ꢁC; (was crys-
tallized from ether/hexane); IR (m, cmꢀ1): 3393 and
3268 (NH), 3069 (CH, aromatic), 2968 and 2929 (CH,
aliphatic), 1665 (C¼¼O), 1643–1489 (C¼¼C and C¼¼N);
1H NMR (400 MHz, CDCl3) d (ppm): 9.44 and 7.39
(m, 2H, 2NH), 7.35–7.15 (m, 10H, ArH), 1.51 and 1.40
(s, 18H, 6CH3); 13C NMR (100 MHz, CDCl3) d (ppm):
162.66 and 161.30 (C¼¼O), 147.20 (C–3), 144.15 (C–5),
118.42 (C–4), 51.68 and 51.01 (NHC), 28.71 and 28.68
(C(CH3)3), 138.90, 130.40, 129.76, 128.92, 128.82,
128.28, 128.11, 125.74; Anal. Calcd. for C25H30N4O2:
C, 71.74; H, 7.22; N, 13.39. Found: C, 71.59; H, 7.25;
6.12; N, 15.46. Found: C, 69.45; H, 6.21; N, 15.42.
1,5-Diphenyl-N3,N4-dipropyl-1H-pyrazole-3,4-dicarboxamide
(9c). (320 mg, 82%); mp 135–136ꢁC; (was crystallized
from chloroform/hexane); IR (m, cmꢀ1): 3361 and 3256
(NH), 3059 (CH, aromatic), 2962 and 2874 (CH, ali-
1
phatic), 1634 (C¼¼O), 1555–1492 (C¼¼C and C¼¼N); H
NMR (400 MHz, CDCl3) d (ppm): 10.37 (m, 2H, 2NH),
7.31–7.15 (m, 10H, ArH), 3.45 and 3.32 (q, J ¼ 6.8 Hz,
4H, 2NHCH2CH2), 1.69–1.59 (m, 4H, 2CH2CH2CH3),
0,94–1,02 (m, 6H, 2CH3); 13C NMR (100 MHz, CDCl3)
d (ppm): 163.26 and 161.52 (C¼¼O), 148.31 (C–3),
142.66 (C–5), 117.32 (C–4), 41.56 and 41.39 (NHCH2),
22.89 and 22.85 (CH2ACH2), 11.73 and 11.55 (CH3),
138.77, 130.53, 129.86, 128.84, 128.42, 128.11, 127.95,
125.61; Anal. Calcd. for C23H26N4O2: C, 70.75; H,
N, 13.38.
1,5-Diphenyl-N3,N3,N4,N4-tetraethyl-1H-pyrazole-3,4-dicar-
boxamide (9g). (322 mg, 77%); mp 134–135ꢁC; (was
crystallized from chloroform/hexane); IR (m, cmꢀ1):
3063 (CH, aromatic), 2978 and 2940 (CH, aliphatic),
1
1656 (C¼¼O), 1617–1496 (C¼¼C and C¼¼N); H NMR
(400 MHz, CDCl3) d (ppm): 7.49–7.15 (m, 10H, ArH),
3.57 and 3.13 (q, J ¼ 7.1 Hz, 8H, 4NCH2), 1.09 and
0.74 (t, J ¼ 7.1 Hz, 12H, 4CH3); 13C NMR (100 MHz,
CDCl3) d (ppm): 164.46 and 162.68 (C¼¼O), 145.63 (C–
3), 139.42 (C–5), 119.97 (C–4), 43.49, 43.37, 40.31,
38.87 (NCH2), 14.60, 13.36, 12.87, 12.44 (CH3),
139.35, 131.53, 129.27, 128.91, 128.69, 128.54, 127.70,
125.02; Anal. Calcd. for C25H30N4O2: C, 71.74; H,
6.71; N, 14.35. Found: C, 70.63; H, 6.79; N, 14.32.
1,5-Diphenyl-N3,N4-diisopropyl-1H-pyrazole-3,4-dicarboxa-
mide (9d). (332 mg, 85%); mp 159–160ꢁC; (was crystal-
lized from ether/hexane); IR (m, cmꢀ1): 3389 and 3249
(NH), 3036 (CH, aromatic), 2967 and 2931 (CH, ali-
1
phatic), 1656 (C¼¼O), 1633–1492 (C¼¼C and C¼¼N); H
NMR (400 MHz, CDCl3) d (ppm): 10.21–10.19 (m, 2H,
2NH), 7.36–7.17 (m, 10H, ArH), 4.34 and 4.18 (m, 2H,
2NHCH(CH3)2), 1.33 and 1.25 (d, J ¼ 6.6 Hz, 12H,
4CH3); 13C NMR (100 MHz, CDCl3) d (ppm): 162.35
and 160.61 (C¼¼O), 148.27 (C–3), 142.76 (C–5), 117.57
(C–4), 41.59 and 40.99 (NHCH), 22.72 and 22.70
(CH(CH3)2), 138.81, 130.52, 129.91, 128.85, 128.82,
128.42, 127.96, 125.72; Anal. Calcd. for C23H26N4O2:
C, 70.75; H, 6.71; N, 14.35. Found: C, 70.55; H, 6.82;
N, 14.37.
7.22; N, 13.39. Found: C, 71.65; H, 7.25; N, 13.41.
1,5,N3,N4,-Tetraphenyl-1H-pyrazole-3,4-dicarboxamide
(9h). (357 mg, 78%); mp 209–210ꢁC; (was crystallized
from chloroform/hexane); IR (m, cmꢀ1): 3465 (NH),
3030 (CH, aromatic), 1655 (C¼¼O), 1599–1489 (C¼¼C
and C¼¼N); 1H NMR (400 MHz, CDCl3) d (ppm):
12.54 and 9.45 (s, 2H, 2NH), 7.85–7.10 (m, 20H, ArH);
13C NMR (100 MHz, CDCl3) d (ppm): 161.64 and
159.35 (C¼¼O), 149.55 (C–3), 142.18 (C–5), 118.14 (C–
4), 139.07, 138.58, 137.13, 130.62, 130.60, 129.50,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

˘
R. Kasımogulları and B. Sec¸kin Arslan
1046
Vol 47
129.22, 129.00, 128.80, 128.78, 128.16, 125.76, 125.13,
123.70, 120.67, 120.33; Anal. Calcd. for C29H22N4O2:
C, 75.97; H, 4.84; N, 12.22. Found: C, 75.86; H, 4.92;
2NH), 8.18–6.52 (m, 18H, ArH); 13C NMR (100 MHz,
DMSO-d6) d (ppm): 162.80 and 160.14 (C¼¼O), 148.52
(C–3), 144.80 and 144.10 (C¼¼C-NO2), 143.25 (C–5),
119.47 (C–4), 142.50, 138.60, 130.11, 129.73, 129.04,
128.12, 126.85, 126.51, 126.45, 125.48, 125.40, 125.16,
122.51, 120.82; Anal. Calcd. for C29H20N6O6: C, 63.50;
N, 12.19.
1,5-Diphenyl-N3,N4-bis(3-(trifluoromethyl) phenyl)-1H-
pyrazole-3,4-dicarboxamide (9i). (434 mg, 73%); mp
202–203ꢁC; (was crystallized from BuOH); IR (m,
H, 3.68; N, 15.32. Found: C, 63.39; H, 3.72; N, 15.33.
1,5-Diphenyl-N3,N4-bis(4-fluorophenyl)-1H-pyrazole-3,4-
dicarboxamide (9m). (400 mg, 81%); mp 227–228ꢁC;
cmꢀ1): 3464 and 3376 (NH), 3070 and 3023 (CH, aro-
1
matic), 1659 (C¼¼O), 1626–1490 (C¼¼C and C¼¼N); H
(was crystallized from BuOH); IR (m, cmꢀ1): 3356
(NH), 3039 and 3000 (CH, aromatic), 1679 (C¼¼O),
1620–1499 (C¼¼C and C¼¼N); 1H NMR (400 MHz,
CDCl3) d (ppm): 12.50 and 9.33 (s, 2H, 2NH), 7.75–
6.98 (m, 18H, ArH); 13C NMR (100 MHz, CDCl3) d
(ppm): 161.62 and 159.15 (C¼¼O), 161.12 and 158.68
(C¼¼C-F), 149.72 (C–3), 141.86 (C–5), 115.19 (C–4),
138.49, 130.53, 129.28, 129.01, 128.86, 128.15, 125.72,
122.57, 122.49, 121.88, 121.81, 116.05, 115.82, 115.41;
Anal. Calcd. for C29H20F2N4O2: C, 70.44; H, 4.08; N,
11.33. Found: C, 70.32; H, 4.12; N, 11.35.
NMR (400 MHz, CDCl3) d (ppm): 12.61 and 9.48 (s,
2H, 2NH), 8.10–7.23 (m, 18H, ArH); 13C NMR (100
MHz, CDCl3) d (ppm): 161.88 and 159.34 (C¼¼O),
150.10 (C–3), 141.56 (C–5), 123.69 and 123.37 (CF3),
116.92 (C–4), 139.41, 138.35, 137.48, 130.49, 129.86,
129.43, 129.23, 129.07, 129.05, 129.01, 128.23, 125.73,
121.77, 121.74, 120.32, 120.28, 117.76, 117.32, 117.28,
116.96; Anal. Calcd. for C31H20F6N4O2: C, 62.63; H,
3.39; N, 9.42. Found: C, 62.48; H, 3.45; N, 9.45.
1,5-Diphenyl-N3,N4-bis(4-ethoxyphenyl)-1H-pyrazole-3,4-
dicarboxamide (9j). (410 mg, 75%); mp 210–211ꢁC;
(was crystallized from PhMe); IR (m, cmꢀ1): 3459 and
3314 (NH), 3020 (CH, aromatic), 2857 (CH, aliphatic),
1
1665 (C¼¼O), 1620–1501 (C¼¼C and C¼¼N); H NMR
1,5-Diphenyl-1H-pyrazole-3,4-dicarbonitrile
(10). Compound 9a of 0.306 g (1 mmol) was dissolved
in 5 mL DMF, and 0.292 mL (4 mmol) SOCl2 was
added. After stirring for 2 h in ice bath and 12 h in
room temperature, some ice water was added to the
mixture. Precipitated solid product was filtered and puri-
fied from ethanol–water mixture by crystallization.
(259 mg, 96%); mp 148–149ꢁC; IR (m, cmꢀ1): 3020
(CH, aromatic), 2231 (CN), 1595–1466 (C¼¼C and
(400 MHz, CDCl3) d (ppm): 12.44 and 9.23 (s, 2H,
2NH), 7.74–6.83 (m, 18H, ArH), 4.27–3.86 (m, 4H,
2OCH2), 1.39–1.47 (m, 6H, 2CH3); 13C NMR (100
MHz, CDCl3) d (ppm): 161.40 and 159.03 (C¼¼O),
156.38 and 155.24 (C¼¼C-OEt), 149.33 (C–3), 142.24
(C–5), 114.55 (C–4), 63.74 and 63.64 (OCH2), 14.89
(CH3), 138.65, 132.23, 130.59, 129.95, 129.60, 129.11,
128.94, 128.68, 128.09, 125.73, 122.45, 121.77, 118.15,
114.91; Anal. Calcd. for C33H30N4O4: C, 72.51; H,
1
C¼¼N); H NMR (400 MHz, CDCl3) d (ppm): 7.52–7.24
(m, 10H, ArH); 13C NMR (100 MHz, CDCl3) d (ppm):
110.80 and 110.77 (CN), 149.05 (C–5), 98.20 (C–4),
137.61, 131.23, 130.03, 129.63, 129.41, 129.16, 128.39,
125.27, 124.92; Anal. Calcd. for C17H10N4: C, 75.54; H,
3.73; N, 20.73. Found: C, 75.65; H, 3.69; N, 20.78.
2,3-Diphenyl-2H-pyrazolo[3,4-d]pyridazine-4,7-dia-
mine (11). Compound 10 of 1 mmol was dissolved in
10 mL absolute ethanol. 0.5 mL anhydrous hydrazine
was added and refluxed for 5 h. The solvent was evapo-
rated and residue compound was washed with ether and
water. The crude product was purified from ethanol–
water by crystallization.
5.53; N, 10.25. Found: C, 72.45; H, 5.58; N, 10.24.
1,5-Diphenyl-N3,N4-di-o-tolyl-1H-pyrazole-3,4-dicarboxa-
mide (9k). (365 mg, 75%); mp 195–196ꢁC; (was crystal-
lized from PhMe); IR (m, cmꢀ1): 3489 and 3381 (NH),
3029 (CH, aromatic), 2922 and 2865 (CH, aliphatic),
1
1658 (C¼¼O), 1615–1485 (C¼¼C and C¼¼N); H NMR
(400 MHz, CDCl3) d (ppm): 11.84 and 9.28 (s, 2H,
2NH), 8.03–7.04 (m, 18H, ArH), 2.42 (s, 6H, 2CH3);
13C NMR (100 MHz, CDCl3) d (ppm): 161.34 and
159.75 (C¼¼O), 149.63 (C–3), 142.60 (C–5), 118.05 (C–
4), 18.62 and 17.92 (CH3), 138.78, 136.52, 135.12,
130.89, 130.71, 130.59, 130.39, 129.60, 129.15, 129.10,
129.02, 128.67, 128.17, 126.93, 126.18, 125.69, 125.64,
124.85, 124.50, 122.93; Anal. Calcd. for C31H26N4O2:
C, 76.52; H, 5.39; N, 11.51. Found: C, 76.61; H, 5.32;
(208 mg, 69%); mp 292–294ꢁC; IR (m, cmꢀ1): 3453
and 3350 (NH), 3057 and 3024 (CH, aromatic), 1626–
1
1492 (C¼¼C and C¼¼N); H NMR (400 MHz, CDCl3) d
(ppm): 7.46–7.18 (m, 10H, ArH), 4.81 (br. s, 4H, NH2);
13C NMR (100 MHz, CDCl3) d (ppm): 149.70 and
148.15 (N¼¼C-NH2), 142.73 (C–3), 138.55, 130.22,
129.30, 129.22, 128.97, 128.78, 128.22, 126.57, 125.27,
114.22; Anal. Calcd. for C17H14N6: C, 67.54; H, 4.67;
N, 27.80. Found: C, 67.43; H, 4.75; N, 27.91.
N, 11.53.
1,5-Diphenyl-N3,N4-bis(4-nitrophenyl)-1H-pyrazole-3,4-
dicarboxamide (9l). (257 mg, 47%); mp 295–297ꢁC;
(was crystallized from EtOH/H2O); IR (m, cmꢀ1): 3468
and 3342 (NH), 3055 and 3006 (CH, aromatic), 1671
Ethyl-1,5-diphenyl-1H-pyrazole-4-carboxylate
(12). Compound 2 of 0.336 g (1 mmol) was heated at
200ꢁC until gas exiting finished. Solid at the bottom
1
(C¼¼O), 1627–1496 (C¼¼C and C¼¼N); H NMR (400
MHz, DMSO-d6) d (ppm): 12.31 and 10.71 (s, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010 Synthesis and Characterization of Some Pyrazole Derivatives of 1,5-Diphenyl-
1H-pyrazole-3,4-dicarboxylic Acid
1047
was washed with ether and water, respectively. The
crude product was purified from ethanol–water mixture
by crystallization. (131 mg, 45%); mp 125–126ꢁC; IR
(m, cmꢀ1): 3064, (CH, aromatic), 2978 (CH, aliphatic),
116.51; 114.02; Anal. Calcd. for C17H12N4O2: C, 67.10;
H, 3.97; N, 18.41. Found: C, 66.93; H, 3.94; N, 18.48.
Acknowledgments. This study was funded by The Scien-
¨
tific and Research Council of Turkey (TUBITAK) with
1
1741 (C¼¼O, ester), 1620–1482 (C¼¼C and C¼¼N); H
Grant No 106T180 and Dumlupinar University Scientific
Research and Project Department.
NMR (400 MHz, DMSO-d6) d (ppm): 8.19 (s, 1H,
CH¼¼N), 7.39–7.21 (m, 10H, ArH), 4.12 (q, J ¼ 7.1 Hz,
2H, CH2), 1.12 (t, J ¼ 7.1 Hz, 3H, CH3); 13C NMR
(100 MHz, DMSO-d6) d (ppm): 162.50 (C¼¼O, ester),
144.61 (C–3), 144.01 (C–5), 120.16 (C–4), 139.15,
130.71, 130.55, 130.12, 129.78, 128.80, 126.45, 123.65;
MS(CI) m/z 293.1 (Mþ1); Anal. Calcd. for
C18H16N2O2: C, 73.95; H, 5.52; N, 9.58. Found: C,
73.82; H, 5.55; N, 9.57.
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