Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid chloride with various hydroxylamines and carbazates

Article abstract of DOI:10.3906/kim-1004-523

The 1H-pyrazole-3-carboxylic acid 2 was converted via reactions of its acid chloride 3 with various hydroxylamine 4a-f and carbazate derivatives 8a-c into the corresponding novel N-substituted-4-benzoyl-1,5-dipenyl-1 H-pyrazole-3-carboxamides 5a-c, N, N-disubstituted-4-benzoyl-1,5-diphenyl-1 H-pyrazole-3-carboxylates 6d,e, 4-benzoyl-N-{[(4-benzoyl-1,5-diphenyl-1H- pyrazol-3-yl)carbonyl]oxy}-N-methyl-1,5diphenyl-1 H-pyrazole-3-carboxamide (7), and 4-benzoyl-N′-(alkoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3- carbohydrazides 9a,b and 10, respectively, in good yields (65%-90%). The reactions of 3 with 4 and 8 in xylene for 8-15 h with catalytic amounts of base led to the formation of the products 5-7, 9, and 10. The structures of all new synthesized compounds were established by the ¹³C-NMR, ¹H-NMR, IR spectroscopic data, and elemental analyses. TUeBITAK.

Full text of DOI:10.3906/kim-1004-523

Turk J Chem
34 (2010) , 859 – 867.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-1004-523
Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-
carboxylic acid chloride with various hydroxylamines
and carbazates
∗
˙
Elif KORKUSUZ, Ismail YILDIRIM
Erciyes University, Department of Chemistry, 38039 Kayseri-TURKEY
e-mail: ismaily@erciyes.edu.tr
Received 08.04.2010
The 1H -pyrazole-3-carboxylic acid 2 was converted via reactions of its acid chloride 3 with various
hydroxylamine 4a-f and carbazate derivatives 8a-c into the corresponding novel N -substituted-4-benzoyl-
1,5-dipenyl-1H -pyrazole-3-carboxamides 5a-c, N, N -disubstituted-4-benzoyl-1,5-diphenyl-1H -pyrazole-3-
carboxylates 6d,e, 4-benzoyl-N -{[(4-benzoyl-1,5-diphenyl-1H -pyrazol-3-yl)carbonyl]oxy}-N -methyl-1,5dip-
henyl-1H -pyrazole-3-carboxamide (7), and 4-benzoyl-Nꢀ -(alkoxycarbonyl)-1,5-diphenyl-1H -pyrazole-3-car-
bohydrazides 9a,b and 10, respectively, in good yields (65%-90%). The reactions of 3 with 4 and 8 in xylene
for 8-15 h with catalytic amounts of base led to the formation of the products 5-7, 9, and 10. The structures
of all new synthesized compounds were established by the 13 C-NMR, 1 H-NMR, IR spectroscopic data, and
elemental analyses.
Key Words: Pyrazole-3-carboxylic acid, nucleophilic substitution, furan-2,3-dione, carbazate, hydroxy-
lamine
Introduction
Furan-2,3-diones in general are considered convenient and versatile synthons in heterocyclic synthesis.1,2 A con-
venient method for their synthesis, the mechanism of reactions, and semi-empirical (AM1 and PM3) and ab initio
(DFT) calculations on the interaction of 4-benzoyl-5-phenyl-2,3-dihydro-2,3-furandione (1) with several semi-
carbazones, ureas, thioureas, and anilides have been reported recently.3−7 The reactions of the furan-2,3-dione
1 and various hydrazines or hydrazones result in new pyrazole-3-carboxylic acids, pyrazolopyridazinones, and
∗Corresponding author
859

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
some of their derivatives. The pyrazole carboxylic acids can be easily transformed into the corresponding acid
chloride, ester, or amide derivatives by the general chemical procedures.8−12 Pyrazoles belong to one of the most
important classes of heterocyclic compounds, which are very significant for medicinal chemistry.13−18 Molecules
of many modern drugs, e.g., antiphlogistic, antifungal, antidiabetic, and analgesic, as well as of insectoacaricides
used in practice, contain a pyrazole ring as a structural fragment.19−28 In view of these important properties,
we decided both to prove the reproducibility of the reaction of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic
acid chloride (3) with some hydroxylamine, 4, and carbazate, 8, derivatives and to extend our investigations
related to preparing new heterocycles, which include the pyrazole ring in their structure. We herein report
the synthesis and characterization of N -substituted 4-benzoyl-1,5-dipenyl-1H-pyrazole-3-carboxamides 5a-
c, N, N -disubstituted-4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylates 6d,e, 4-benzoyl-N -{[(4-benzoyl-1,5-
diphenyl-1H -pyrazol-3-yl)carbonyl]oxy}-N-methyl-1,5-diphenyl-1H-pyrazole-3-carboxamide (7) (see Scheme
1), 4-benzoyl-Nꢀ -(alkoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carbohydrazides 9a,b, and 4-benzoyl-Nꢀ -[(4-
benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]-1,5-diphenyl-1H-pyrazole-3-carbohydrazide (10) by the reac-
tion of the pyrazole-3-carboxylic acid chloride 3 with the corresponding hydroxylamine 4a-f and carbazate
derivatives 8a-c (see Scheme 2).
Experimental
Melting points are uncorrected and were recorded on an Electrothermal 9200 digital melting point apparatus.
Microanalyses were performed on a Leco-932 CHNS-O Elemental Analyzer. A Shimadzu FT-IR-8400 model
spectrophotometer was used for IR spectra (in the range of 400-4000 cm−1 region), using ATR techniques. The
1 H- and 13 C-NMR spectra were measured with a Bruker Avance III 400 MHz spectrometer and the chemical
shifts were recorded in ppm units. After completion of the reactions, solvents were evaporated with a rotary
evaporator (Buchi RE model 111). The reactions were followed by TLC using DC Alufolien Kieselgel 60 F254
Merck and a Camag TLC lamp (254/366 nm). Solvents and all other chemical reagents were purchased from
commercial suppliers and were of reagent grade quality. Solvents were dried by refluxing with the appropriate
drying agents and distilled before use.
General procedure for the synthesis of compounds 5-10
Appropriate amounts of the acid chloride 3 (0.50 g, 1.30 mmol) and the corresponding hydroxylamine, 4, or
carbazate, 8, derivatives (molar ratio 1:1 or 1:2) were dissolved in xylene and refluxed together with catalytic
amounts of pyridine for 8-15 h. Then the solution was cooled to room temperature and the corresponding
reaction products 5-7, 9, and 10 were obtained after evaporation of the solvent and triturating with diethyl
ether or petroleum ether. After suction filtration, the crude products were recrystallized from ethanol and dried
on P2 O5 .
4-Benzoyl-N-benzyloxy-1,5-diphenyl-1H-pyrazole-3-carboxamide (5a):
Compound 5a was prepared according to the general procedure with a reflux time of 10 h (O-benzylhydroxyla-
mine) resulting in 79% yield (0.48 g); mp 182 ◦ C. FT IR (ATR, cm−1)ν : 3179 (N-H), 3050 (arom. C-H), 2950
860

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
(aliph. C-H), 1652, 1638 (C=O), 1589, 1583, 1502, 1446 (phenyl and pyrazole rings C... C, C... N). 1 H-NMR
(400 MHz, DMSO-d6)δ: 12.00 (br, 1H, NH), 8.00-7.24 (m, 20H, ArH), 4.80 ppm (s, 2H, CH2). 13 C-NMR
(100 MHz, DMSO-d6)δ: 190.82 (PhC=O), 158.72 (-NC=O) 144.32 (C-5), 143.75 (C-3), 138.94, 138.15, 136.10,
133.70, 130.12, 129.68, 129.53, 129.46, 129.23, 129.13, 128.96, 128.87, 128.70, 128.20, 128.04, 126.43, 126.07,
121.95 (C-Ph), 77.46 ppm (CH2). Anal. calcd. for C30 H23 N3 O3 (473.52 g/mol); C, 75.80; H, 9.14; N, 4.61.
Found: C, 75.40; H, 8.86; N, 4.87.
4-Benzoyl-N-methoxy-N-methyl-1,5-diphenyl-1H-pyrazole-3-carboxamide (5b):
Compound 5b was prepared according to the general procedure with a reflux time of 8 h (N ,O-dimethylhydroxy-
lamine) resulting in 90% yield (0.45 g); mp 170 ◦ C. FT IR (ATR, cm−1)ν : 3042 (arom. C-H), 2928, 2881
(aliph. C-H), 1659, 1639 (C=O), 1593, 1582, 1510, 1445 (phenyl and pyrazole rings C... C, C... N). 1 H-NMR
(400 MHz, CDCl3) δ: 7.90-7.20 (m, 15H, ArH), 3.81 (s, 3H, CH3), 3.30 ppm (s, 3H, CH3). 13 C-NMR (100
MHz, CDCl3)δ: 190.06 (PhC=O), 146.93 (-NC=O), 144.19 (C-5), 138.97, 138.28, 132.49, 130.34, 129.32, 129.15,
128.89, 128.46, 128.28, 128.24, 128.17, 128.04, 125.40 (C-Ph), 61.03 (OCH3) 29.59 ppm (NCH3). Anal. calcd.
for C25 H21 N3 O3 (411.45 g/mol): C, 72.98; H, 5.14; N, 10.21. Found: C, 73.29; H, 5.05; N, 9.88.
4-Benzoyl-N-(4-nitrobenzyloxy)-1,5-diphenyl-1H-pyrazole-3-carboxamide (5c):
Compound 5c was prepared according to the general procedure with a reflux time of 12 h (O-(4-nitrobenzyl)hyd-
roxylamine) resulting in 76% yield (0.51 g); mp 197 ◦ C. FT IR (ATR, cm−1)ν : 3200 (N-H), 3055 (arom. C-H),
2953 (aliph. C-H), 1665, 1636 (C=O), 1600, 1578, 1514, 1442 (phenyl and pyrazole rings C... C, C... N). 1 H-
NMR (400 MHz, DMSO-d6)δ: 10.85 (1H, NH), 7.90-6.99 (m, 19H, ArH), 5.40 ppm (s, 2H, CH2). 13 C NMR
(100 MHz, DMSO-d6)δ: 192.00 (PhC=O), 159.20 (-NC=O), 149.60 (C-5), 147.62 (C-NO2), 147.22, 146.68,
144.17, 143.86, 139.14, 133.69, 130.33, 129.71, 129.58, 129.45, 128.96, 128.70, 128.48, 128.13, 126.47, 123.79,
118.69 (C-Ph), 76.06 ppm (CH2). Anal. calcd. for C30 H22 N4 O5 (518.52 g/mol); C, 69.49; H, 4.28; N, 10.81.
Found: C, 69.80; H, 4.25; N, 10.59.
N,N -Dimethylamino 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylate (6d):
Compound 6d was prepared according to the general procedure with a reflux time of 12 h (N, N -dimethylhyd-
roxylamine) resulting in 77% yield (0.41 g); mp 198 ◦ C. FT IR (ATR, cm−1)ν : 3068 (arom. C-H), 2978 (aliph.
C-H), 1698, 1678 (C=O), 1589, 1512, 1494, 1442 (phenyl and pyrazole rings C... C, C... N).1 H-NMR (400 MHz,
CDCl3)δ: 7.98-7.10 (m, 15H, ArH), 2.60 ppm (s, 6H, CH3).13 C-NMR (100 MHz, CDCl3)δ: 191.26, (PhC=O),
162.71 (-OC=O), 143.41 (C-5), 142.96, 139.07, 138.10, 133.86, 130.07, 129.69, 129.55, 129.50, 129.22, 129.09,
128.88, 128.22, 126.27, 123.25 (C-Ph), 40.01 ppm (CH3). Anal. calcd. for C25 H21 N3 O3 (411.45 g/mol): C,
72.98; H, 5.14; N, 10.21. Found: C, 73.16; H, 4.94; N, 10.00.
861

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
N,N -Dibenzylamino 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylate (6e):
Compound 6e was prepared according to the general procedure with a reflux time of 15 h (N, N -dibenzylhydroxy-
lamine) resulting in 79% yield (0.34 g); mp 202 ◦ C. FT IR (ATR, cm−1)ν : 3049 (arom. C-H), 2938 (aliph.
C-H), 1696, 1643 (C=O), 1544, 1514, 1498, 1443 (phenyl and pyrazole rings C... C, C... N).1 H-NMR (400 MHz,
DMSO-d6)δ: 7.80-7.10 (m, 25H, ArH), 4.00 ppm (s, 4H, CH2).13 C-NMR (100 MHz, DMSO-d6)δ: 192.17,
(PhC=O), 164.49 (-OC=O), 149.85 (C-5), 141.97, 141.08, 139.65, 138.96, 135.51, 133.06, 131.21, 130.44, 129.92,
129.41, 129.29, 129.21, 129.11, 129.06, 128.90, 128.81, 128.75, 128.50, 128.41, 127.94, 127.52, 127.24, 126.68,
125.92, 125.34, 122.84 (C-Ph), 64.40 ppm (CH2). Anal. calcd. for C37 H29 N3 O3 (563.65 g/mol); C, 78.84; H,
5.19; N, 7.46. Found: C, 78.86; H, 5.15; N, 7.50.
4-Benzoyl-N-{[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]oxy}-N-methyl-
1,5-diphenyl-1H-pyrazole-3-carboxamide (7):
Compound 7 was prepared according to the general procedure with a reflux time of 15 h (N -methylhydroxylami-
ne) resulting in 67% yield (0.48 g); mp 156 ◦ C. FT IR (ATR, cm−1)ν : 3057 (arom. C-H), 2980 (aliph. C-H),
1773, 1707, 1658 (C=O), 1585, 1545, 1457 (phenyl and pyrazole rings C... C, C... N). 1 H-NMR (400 MHz,
DMSO-d6)δ: 7.90-7.08 (m, 30H, ArH), 2.20 ppm (s, 3H, CH3). 13 C-NMR (100 MHz, DMSO-d6)δ: 190.91,
190.48 (PhC=O), 160.10 (-OC=O), 159.90 (-NC=O), 143.82, 143.73 (C-5, C-5’), 142.57, 139.57, 139.16, 138.64,
138.10, 137.75, 133.43, 132.78, 130.06, 129.95, 129.83, 129.72, 129.49, 129.36, 129.14, 129.09, 128.83, 128.62,
128.46, 128.43, 128.22, 128.09, 127.87, 127,50, 125.66, 125.48, 125.09, 124.31, 124.18 (C-Ph), 29.03 ppm (CH3).
Anal. calcd. for C47 H33 N5 O5 (747.80 g/mol); C, 75.49; H, 4.45; N, 9.37. Found: C, 75.18; H, 4.71; N, 9.33.
4-Benzoyl-Nꢀ-(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carbohydrazide (9a):
Compound 9a was prepared according to the general procedure with a reflux time of 10 h (ethyl carbazate)
resulting in 75% yield (0.32 g); mp 128 ◦ C. FT IR (ATR, cm−1)ν : 3261 (N-H), 3057 (arom. C-H), 2984 (aliph.
C-H), 1734, 1691, 1666 (C=O), 1593, 1550, 1491, 1450 (phenyl and pyrazole rings C... C, C... N). 1 H-NMR (400
MHz, CDCl3)δ: 9.65 (s, 1H, NH), 8.92 (s, 1H, NH), 7.90-7.00 (m, 15H, ArH), 4.21 (q, 2H, CH2), 1.34 ppm (t,
3H, CH3). 13 C-NMR (100 MHz, CDCl3)δ: 191.35 (PhC=O), 159.97, 156.08 (NC=O), 144.08 (C-5), 142.99
(C-3), 138.78, 133.18, 129.82, 129.51, 129.31, 129.08, 128.61, 128.29, 127.79, 125.39, 125.31, 122.34 (C-Ph),
62.25 (CH2), 14.33 ppm (CH3). Anal. calcd. for C26 H22 N4 O4 (454.48 g/mol); C, 68.71; H, 4.88; N, 12.33.
Found: C, 68.73; H, 4.87; N, 12.36.
4-Benzoyl-Nꢀ-(benzyloxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carbohydrazide
(9b):
Compound 9b was prepared according to the general procedure with a reflux time of 12 h (benzyl carbazate)
resulting in 70% yield (0.27 g); mp 137 ◦ C. FT IR (ATR, cm−1)ν : 3268 (N-H), 3058 (arom. C-H), 2986 (aliph.
C-H), 1739, 1694, 1667 (C=O), 1596, 1552, 1491, 1447 (phenyl and pyrazole rings C... C, C... N). 1 H-NMR (400
MHz, DMSO-d6)δ: 10.32 (s, 1H, NH), 9.30 (s, 1H, NH), 7.80-7.08 (m, 20H, ArH), 5.06 ppm (s, 2H, CH2). 13 C-
862

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
NMR (100 MHz, DMSO-d6)δ: 191.34 (PhC=O), 160.53, 156.63 (NC=O), 144.18 (C-5), 142.93 (C-3), 139.03,
138.07, 133.73, 130.03, 129.69, 129.52, 129.49, 129.24, 128.98, 128.90, 128.80, 128.30, 128.23, 126.40, 122.42
(C-Ph), 68.00 ppm (CH2). Anal. calcd. for C31 H24 N4 O4 (516.55 g/mol); C, 72.08; H, 10.85; N, 4.68. Found:
C, 72.07; H, 10.84; N, 4.70.
4-Benzoyl-Nꢀ-[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]-1,5-diphenyl-1H-
pyrazole-3-carbohydrazide (10):
Compound 10 was prepared according to the general procedure with a reflux time of 8 h (tert-butyl carbazate)
resulting in 65% yield (0.50 g); mp 193 ◦ C. FT IR (ATR, cm−1)ν : 3167, 3120 (N-H), 3022 (arom. C-H), 2941,
2897 (aliph. C-H), 1664, 1620 (C=O), 1595, 1537, 1488, 1452 (phenyl and pyrazole rings C... C, C... N). 1 H-
NMR (400 MHz, DMSO-d6)δ: 10.32 (s, 2H, NH), 7.92-7.00 (m, 30H, ArH). 13 C-NMR (100 MHz, DMSO-d6)δ:
191.19 (PhC=O), 160.01 (NHC=O), 143.83 (C-5), 143.33 (C-3), 139.04, 138.10, 133.68, 130.02, 129.68, 129.51,
129.46, 128.90, 128.25, 126.33, 122.40 ppm (C-Ph). Anal. calcd. for C46 H32 N6 O4 (732.78 g/mol); C, 75.40;
H, 4.40; N, 11.47. Found: C, 75.38; H, 4.42; N, 11.47.
Results and discussion
Treatment of the yellow furandione 1 with phenylhydrazine under reflux in benzene for 3 h yielded the
corresponding white 1H -pyrazole-3-carboxylic acid 2.8 Compound 2 can easily be transformed into the 1H -
pyrazole-3-carboxylic acid chloride 3 by usual chemical procedures.9 Substituted furan-2,3-dione 1, -acid 2 and
-acid chloride 3, which were used as important initial materials in the synthesis of the target heterocycles, were
prepared using the literature procedures (Scheme 1).1,8,9,29
The reaction of compound 3 with various hydroxylamines 4 and carbazates 8 in the presence of a
catalytic amount of pyridine proceeded rapidly by refluxing in xylene and was completed after 8-15 h to
afford the corresponding carboxamide, carboxylate, and carbohydrazide derivatives 5-7, 9, and 10 in good
yields (65%-90%), without opening the pyrazole ring. In order to make the reaction selective, we had to
determine the parameters, in other words the reaction pathways, leading to such results. The excellent yield
of the reaction can be explained by the chemical behavior of compound 3 towards H-active nucleophiles, such
as hydroxylamines and carbazates. It should start with a nucleophilic attack of the nitrogen and/or oxygen
atoms’ lone pair electrons of the hydroxylamine to the antibonding (π *) orbital at the carbonyl carbon at C-3
position of the pyrazole ring. The new products 5-7, 9, and 10 obtained arise followed by the elimination of
hydrogen chloride. Although we have not studied this issue further, we assume that the reaction occurs under
thermodynamic control. The byproducts formed this way are removed when the raw products are treated with
diethyl ether. Previously, analogous reactions and their mechanisms have been reported with hydrazines, ureas,
diamines, aminophenols, thiosemicarbazides, and the corresponding open chain compounds.9−17 The structure
of compound 5a, which was obtained in 79% yield in the first experiment, was established by spectral data,
in particular by the presence of carbonyl (benzoyl and amidic) characteristic bands of 5a (FT IR: 1652 s,
30
1638 s. cm−1). The broad absorption of N-H group was at 3179 cm−1
,
and absorption bands of various
intensity were observed in the spectra of 5a assigned to skeleton bands of benzene or pyrazole rings, together
863

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
with N-H bending vibrations, at 1589-1446 cm−1 . In the 1 H-NMR spectra, the NH protons resonated at
12.00 ppm as a broad singlet integrating for one proton. Moreover, proton signals due to the OCH2 group of
this compound resonated at 4.80 ppm as a singlet integrating for the 2 protons. Different aromatic protons
were found in the usual range (at 8.00-7.24 ppm). In the 13 C-NMR spectrum of 5a, the characteristic signal
belonging to carbonyl carbon appeared at 190.82 (benzoyl) and 158.72 ppm (amidic). Complete 13 C-NMR data
are given in the Experimental part. These results are in full agreement with a similar finding with substituted
1H -pyrazole-3-carboxamides and -3-carboxylates.8−16,25,26
O
Ph
Ph
O
O
O
O
O
O
O
Ph
OH
Ph
[Ref. 8]
Ph
O
H C
N
N
N
N
O
Ph
3
Ph
Ph
O
N
Ph
2
N
Ph
N
Ph
1
7
4f
[Ref. 9]
xylene, reflux
O
O
N
O
O
N
O
O
NRR'
OR''
Ph
Ph
Ph
Ph
Ph
Cl
O
NR
4d, e
4a-c
xylene, reflux
+
R''O NRR'
N
xylene, reflux
Ph
4a-f
d
N
N
Ph
3
N
Ph
6d, e
Ph
5a-c
c
-H
4-6
R
a
-H
e
b
f
-CH3
-CH
-CH Ph
-CH
3
2
3
-H
-H
R'
-CH
-H
-H
-H
-H
-CH Ph
2
3
-CH Ph-NO
-H
-CH
R'' -CH Ph
2
2
3
2
Scheme 1. Synthetic pathway for the preparation of compounds 3-7.
Interaction of the pyrazole-3-carboxylic acid chloride 3 with 4d,e at reflux results in the corresponding new
compounds 6d,e, in good yields (77% and 79%, respectively). Surprisingly, using N ,N -disubstituted hydroxy-
lamine derivatives 4d,e in reactions with 3, the 1H -pyrazole-3-carboxylates 6d,e were obtained exclusively. In
addition, the reaction of 3 with N -methyl hydroxylaminehydrocloride (4f) in refluxing xylene, together with
catalytic amounts of pyridine afforded 4-benzoyl-N -{[(4-benzoyl-1,5-diphenyl-1H-pyrazol-3-yl)carbonyl]oxy}-
N -methyl-1,5-dipheny-1H-pyrazole-3-carboxamide (7). The moderate to good yield of the reactions can be
explained by the chemical behavior of acid chlorides, similar to the behavior of the compound 3 towards O-
and N−nucleophiles.9−15 The formation of 7 can easily be explained by a nucleophilic attack on the carbonyl
groups of 2 molecules of the acid chloride 3. It appears that this process can be followed by elimination of 2
molecules of hydrogen chloride to give 7, whose formation is confirmed by TLC using authentic specimens of
7 and strongly supported by the results of analytical as well as spectroscopic measurements. The IR spectrum
of 7 showed characteristic absorption bands at 1773, 1707, and 1658 cm−1 for carbonyl groups (ester, amidic,
and benzoyl). The 1 H-NMR signals were observed at δ 7.90-7.08 ppm (m, ArH) and 2.20 ppm (s, CH3) and
864

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
the 13 C-NMR signals at δ 190.91, 190.48 (benzoyl), 160.10 (ester), 159.91 (amide), 143.73, 143.82 (C-5, C-5’),
142.57-124.18 (arom. C’s), and 29.03 ppm (CH3).
O
O
O
O
O
O
O
R
O
O
O
NH
NH
Ph
Cl
O
Ph
Ph
Ph
NH
NH
Ph
8c
8a, b
NH
2
+
N
NH
R''O
N
N
Ph
Ph
N
N
Ph
N
Ph
N
8a-c
N
Ph
9a, b
Ph
10
Ph
8c
3
O
O
O
a
-Et
b
8, 9
R
c
O
H3C
NH
Ph
NH
CH3
CH3
-benzyl
-t-butyl
N
Ph
N
Ph
11
Scheme 2. Synthesis of substituted 1H -pyrazole-3-carbohydrazide derivatives 9, 10.
4-Benzoyl-Nꢀ -(ethoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carbohydrazide 9a was synthesized by the
reaction of ethyl carbazate (8a) and the compound 3, which could be obtained by the elimination of hydrogen
chloride (see Scheme 2). The structures of the compounds 9 were confirmed from IR and 1 H- and 13 C-NMR
spectroscopic data. The IR spectrum of 9a exhibited ester and amidic carbonyls at 1734 and 1691 cm−1
.
The 1 H-NMR spectrum showed singlets at 9.65 and 8.92 ppm due to NH protons. The aromatic protons
resonated as multiplets in the range of 7.90-7.00 ppm. Further confirmation also came from 13 C-NMR data (for
details see the Experimental). However, analytical and spectroscopic investigations clearly indicated that the
reaction of compound 3 with tert-butyl carbazate gave the new product 10 instead of the expected 4-benzoyl-
Nꢀ -(tert-butoxycarbonyl)-1,5-diphenyl-1H-pyrazole-3-carbohydrazide 11. In this reaction, tert-butyl carbazate
behaved as a binucleophile. It is assumed that this chemical behavior and the comparatively low yields could
be attributed to the steric hindrance of tert-butyl group. tert-Butyl carbazates are less reactive because bulky
groups present a strong hindrance to the approaching substrate. Furthermore, the tert-butoxycarbonyl group
is a weak base and good leaving group. Thus, the tert-butyl substituent is very bulky and used in chemistry
for kinetic stabilization together with other bulky groups. The effect that the tert-butyl group exerts on the
progress of a chemical reaction is called the tert-butyl effect. This effect is illustrated in many reactions, where
the tert-butyl substituent causes a reaction rate acceleration by compared to hydrogen as the substituent.31,32
Therefore, addition of tert-butyl carbazate binucleophile to the acid chloride 3 usually starts with nucleophilic
attack at the acid chloride moieties in compound 3. Therefore, the new product 10 obtained arises from the
sequential attacks of the carbazate at the acid chloride moieties of 2 respective molecules of 3, followed by the
elimination of hydrogen chloride.11 The IR spectra of the compound 10 showed characteristic absorption bands
at 3167, 3120 cm1 (N-H) and 1664, 1620 cm1 (C=O). The structure of compound 10 was evidenced by the
disappearance of tert-butyl protons in 1 H-NMR spectra and appearance of 2 NH protons at 10.32 ppm as a
singlet. The values of the elemental analysis were found to be in good agreement ( 0.3%) with the calculated
values.
865

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Reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic..., E. KORKUSUZ, I. YILDIRIM
Conclusions
In this study, we have developed convenient preparative procedures for the efficient synthesis of previously
unknown pyrazole-3-carboxamides and pyrazole-3-carboxylates derivatives. The above approach has been
proved very useful for the construction of novel heterocycles of potential pharmacological interest. The newly
synthesized compounds attract interest as potential biologically active substance, as well as precursors and
reagents for the design of complex polyfunctional structures.
Acknowledgements
Financial support from the Scientific Research Projects Chairmanship of Erciyes University is gratefully ac-
knowledged. The authors dedicate this paper to the memory of Prof. Dr. Yunus Akc¸amur.
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