Synthesis and electrochemical behavior of some 1H-3-methyl-4- ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles

Article abstract of DOI:10.1007/s00706-005-0469-6

1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles are key intermediates in obtaining various heterocyclic systems including pyrazolotriazoles. We present the voltammetric behavior of these compounds in nonaqueous media, with the following par

Full text of DOI:10.1007/s00706-005-0469-6

Monatshefte f€ur Chemie 137, 737–744 (2006)
DOI 10.1007/s00706-005-0469-6
Synthesis and Electrochemical Behavior
of Some 1H-3-Methyl-4-ethoxycarbonyl-
5-(benzylidenehydrazino)pyrazoles
Liviu V. Costea1;ꢀ, Vasile N. Bercean1, Valentin Badea1,
Klaus Gerdes2, and Ulrich Jordis2
1
Faculty of Industrial Chemistry and Environmental Engineering, University ‘‘Politehnica’’
Timisꢀ
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
oara, Timis
ꢀoara, Romania
2
Received October 13, 2005; accepted (revised) November 21, 2005
Published online May 5, 2006 # Springer-Verlag 2006
Summary. 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles are key intermediates
in obtaining various heterocyclic systems including pyrazolotriazoles. We present the voltammetric
behavior of these compounds in nonaqueous media, with the following para substituents grafted on the
benzene ring: –N(CH3)2, –OH, –OCH3, –F, –Cl, –CF3, –NO2, as well as of the novel compounds with
–Br, –I, and –SCH3 in the para position, in order to elucidate the influence of the various substituents
on the mechanism of anodic oxidation.
Keywords. Cyclic voltammetry; Donor-acceptor effects; Electrochemistry; Heterocycles; Linear free
energy relationship.
Introduction
1H-3-Methyl-4-ethoxycarbonyl-5-(arylidenehydrazino)pyrazoles 1–11 are key
intermediates in obtaining 1H-3-aryl-6-methyl-7-ethoxycarbonyl-pyrazolo[5,1-
c][1,2,4]triazoles 12–22 (Scheme 1). The latter compounds are used as precursors
of color photographic light sensitive materials [1], toners, and ink jet printer
dyes [2].
In the presence of bromine and sodium acetate in glacial acetic acid, the
hydrazones substituted with –NO2, –Cl, and methyl yield the corresponding pyr-
azolotriazoles [1]. If the substrate contains substituents like –OH, –OCH3, the
non-desired brominated pyrazolotriazoles 14, 15, and 22 are formed (Scheme 1)
[3]. In order to avoid this formation, we intended to obtain the desired compounds
ꢀ
Corresponding author. E-mail: lcostea@online.ro

738
L. V. Costea et al.
Scheme 1
by electrosynthesis [4–8]. Because, to our knowledge, no electrochemical investi-
gation of these compounds has been published so far, we present the results of an
electrochemical investigation of the substituted 1H-3-methyl-4-ethoxycarbonyl-5-
(benzylidenehydrazino)pyrazoles 1–11 in nonaqueous media in order to elucidate
the mechanism of anodic oxidation. Intrinsic knowledge on the electrochemical
processes that take place at the anode could help finding a more convenient way to
obtain the desired pyrazolotriazoles by electrosynthesis.
Results and Discussions
The electrochemical behavior of the (benzylidenehydrazino)pyrazoles 1–11 in
acetonitrile was investigated by cyclic voltammetry. The cyclic voltammograms
of 1–11 showed two to three non-reversible oxidation peaks (Fig. 1) at potentials
summarized in Table 1.
We believe that the substituents grafted on the phenyl ring play an important role
in the formation and stability of the radical cations that may be generated during the
anodic oxidation of the substrate (Scheme 2). The data of Table 1 reveal that the
anodic peak potential (EpA) is shifted to more positive values due to the presence of
the electron-withdrawing groups on the para position of the phenyl ring and the
reverse is observed for electron-donating groups. This is because oxidation will be
thermodynamically more facile when electron density flows to the benzene ring
leading to the stabilization of the positive charge of the cation radical [9].
Under the given conditions and according to the preliminary results obtained in
the controlled potential electrolysis of 1H-3-methyl-4-ethoxycarbonyl-5-(benzyli-
denehydrazino)pyrazole (1) [8] resulting in the formation of the pyrazolotriazole
12, we believe that the ꢀ-state prevails thus having a positive reaction center
localized at the hydrazonic carbon atom (Scheme 2).
The non-reversibility of the first oxidation peak of the (benzylidene-
hydrazino)pyrazoles 1–11 may arise from the loss of protons from the iminium-

Synthesis and Electrochemical Behavior
739
Fig. 1. Cyclic voltammogram of 4 in anhydrous acetonitrile; conditions: substrate concentration
c ¼ 2 ꢂ 10ꢁ3 mol ꢂ dmꢁ3, supporting electrolyte c ¼ 0.1 mol ꢂ dmꢁ3 tetra-n-butylammonium tetrafluo-
rorborate, solvent anhydrous acetonitrile, working electrode Pt, auxiliary electrode Pt wire, reference
electrode Ag=AgCl, scan rate 50 ꢂ 10ꢁ3 V ꢂ sꢁ1; inset: cyclic voltammogram of 1 under the same
experimental conditions
Table 1. Electrochemical data from cyclic voltammetry for the para-substituted (benzylidenehydra-
zino)pyrazoles 1–11a
DEX1b=V
DlogKX1
ꢀpþ
c
Substituent
EpA1=V
EpA2=V
–H
1.000
0.660
0.850
0.890
1.127
1.003
1.025
1.120
1.017
1.038
0.898
1.600
1.190
1.360
1.400
–
0.000
0.340
0.000
5.758
0.00
ꢁ1.70
ꢁ0.92
ꢁ0.78
0.79
–N(CH3)2
–OH
–OCH3
–NO2
–F
0.150
2.540
0.110
1.863
ꢁ0.127
ꢁ0.002
ꢁ0.025
ꢁ0.120
ꢁ0.017
ꢁ0.038
0.103
ꢁ2.151
ꢁ0.042
ꢁ0.423
ꢁ2.032
ꢁ0.288
ꢁ0.635
1.736
1.563
1.638
1.800
1.640
1.638
1.330
ꢁ0.07
0.11
–Cl
–CF3
–Br
0.61
0.15
–I
0.14
–SCH3
ꢁ0.60
a
Conditions: compound concentration c ¼ 2 ꢂ 10ꢁ3 mol ꢂ dmꢁ3
,
ref. Ag=AgCl, scan rate
b
c
50 ꢂ 10ꢁ3 V ꢂ sꢁ1
;
DEX1 ¼ EpA1H ꢁ EpA1X
;
data taken from Ref. [17]
like nitrogen atom after oxidation occurs (Scheme 2), and thus the system is likely
non-chemically reversible. We can assume that the first oxidation exhibits clas-
sical EC mechanism behavior [10], and if the rate of chemical reaction is much
faster than the rate of electrochemical reaction, the electrochemical step becomes

740
L. V. Costea et al.
Scheme 2
pseudo-first-order, albeit non-reversible. This is most likely the case for our sys-
tems, as changes in scan rate for the cyclic voltammograms have no effect on the
lack of observed reduction peaks and little effect on the position of EpA.
It has been shown [11] that if EpA is measured for each substituent by cyclic
voltammetry using the same scan rate, working electrode, electrolyte concentra-
tion, and compound concentration, the differences in the oxidation potentials EpA
should reasonably reflect free energy differences and allow for a correlation using
the Hammett linear free energy relationship [12].
The potential difference between the oxidation peaks of the unsubstituted
(benzylidenehydrazino)pyrazole 1 and the (benzylidenehydrazino)pyrazole with
the substituent X attached to the benzene ring (Eq. (1)) can be used to obtain the
following correlations [11]:
DEX ¼ EpAH ꢁ EpAX
DEX ¼ ð2:3 ꢂ RT=nFÞ ꢂ D log KX
D log KX ¼ ꢀþꢂ ꢁþ
ð1Þ
ð2Þ
ð3Þ
Plotting DlogKX for the first oxidation potentials against the resonance-
enhanced substituent constants ꢀþp (Fig. 2) gives a linear correlation of the obtained
data points (e.g. correlation coefficient R ¼ 0.99). A positive value of ꢁ indicates
that the reaction is enhanced by electron-withdrawing groups, whereas a negative
value denotes enhancement by electron-donating groups. The magnitude of ꢁ indi-
cates whether the reaction is more or less sensitive to substituent electronic effects
than benzoic acid dissociation [13].
The Hammett plot DlogKX against ꢀþp gave a ꢁþ value of about ꢁ3.10 suggest-
ing a direct influence of the substituents attached to the phenyl ring on the mecha-
nism of anodic oxidation of the studied compounds. The linear correlation between
the resonance enhanced substituent constants and DlogKX shows a direct influence
of the para – substituents on the mechanism of anodic oxidation, reflected in the

Synthesis and Electrochemical Behavior
741
Fig. 2. Hammett plots of DlogKX vs. ꢀþp for the first oxidation peaks of the substituted (benzyl-
idenehydrazino)pyrazoles 1–11 in anhydrous acetonitrile; exp. data , linear regression (solid line)
relatively large value of the reaction constant ꢁ. This can be explained by a sig-
nificant delocalization of charge onto the phenyl ring in the molecular orbitals of
the corresponding radical cations 25 (Scheme 2). The predictive capabilities of the
correlation between DlogKX and ꢀþp have not been tested yet but there is a good
chance that the predictions will hold since R closely approaches 1.
Following the electrochemical investigation of 1–11, we conducted a con-
trolled potential electrolysis of 1 at the potential of the first oxidation peak [8].
The formation of the pyrazolotriazole 12 as a result of the anodic oxidation comes
to confirm the proposed EC mechanism.
Experimental
The study of the electrochemical properties of the (benzylidenehydrazino)pyrazoles was conducted by
recording the cyclic voltammograms over the potential range of interest. While the anodic polarization
limit was set to about 2 V vs. ref., the solvent-supporting electrolyte system consisted of dry acetonitrile
and tetra-n-butylammonium tetrafluoroborate. Solutions for all voltammetric analyses were deoxyge-
nated by bubbling with dry N2 and this atmosphere was maintained throughout the experiments.
The working electrode consisted of a Pt disc (d ¼ 3 mm), the auxiliary electrode was a Pt wire.
The cyclic voltammetry experiments were performed using a Princeton Applied Research model
M273A potentiostat in a single compartment cell with 7 cm3 of electrolyte solution containing
c ¼ 2 ꢂ 10ꢁ3 mol ꢂ dmꢁ3 of substrate at rt. No correction was applied to compensate for the solution
resistance. The voltammograms were recorded and processed using the EG&G M273 software. All
potentials were measured with respect to the Ag=AgCl electrode at rt, which corresponds to a potential
difference from that of Fc=Fcþ (Fc¼ ferrocene) standard redox couple [14, 15] of þ0.45V in
DMSO=tetra-n-butylammonium tetrafluororborate.
Melting points were recorded with a Boetius PHMK (Veb – Analytik Dresden) apparatus;
thin layer chromatography was performed using 60F254 silica gel plates (Merck) and a mixture of

742
L. V. Costea et al.
benzene:ethyl acetate¼ 1:1 as eluant. Elemental analyses (C, H, N) were conducted using the Perkin
Elemer 2400 Elementar Analyser; their results were found to be in good agreement (ꢃ0.2%) with the
calculated values.
The purity of the compounds was >99%, as determined by HPLC. HPLC analyses were conducted
with a Merck Chromolith Performance 2 column, using acetonitrile=H2O as eluant. IR spectra were
recorded with a Jasco FT=IR-410 Infrared Spectrophotometer using KBr disks and Bruker Avance 300
spectrometers were used for 1H and 13C NMR spectroscopy. All chemical shift values are given vs. the
TMS internal reference.
Anhydrous DMSO (analytical grade, Fluka) and methanol (for synthesis Fluka) were used as
purchased.
General Preparation Method for the Substituted 1H-3-Methyl-4-ethoxycarbonyl-5-
(benzylidenehydrazino)pyrazoles 1–11 [16]
A mixture of 25mmol 1H-3-methyl-4-ethoxycarbonyl-5-hydrazino-pyrazole chlorohydrate, 25 mmol
substituted benzaldehyde, and 75 cm3 absolute ethyl alcohol is refluxed for 2–4 h under chromato-
graphic control. The turbid solution formed is filtered over active C and the filtrate is diluted with
75cm3 cold H2O (0–5ꢄC). The resulting suspension is filtered off and the crude product is recrystal-
lized from an adequate solvent.
1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazole (1)
White powder, mp 165–167ꢄC (C2H5OH) (Ref. [1] 167ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-N,N-dimethylaminobenzylidenehydrazino)pyrazole (2)
White powder, mp 198–200ꢄC (Ref. [16] 198–200ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-hydroxybenzylidenehydrazino)pyrazole (3)
White powder, mp 212–216ꢄC (CH3OH) (Ref. [16] 212–216ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-methoxybenzylidenehydrazino)pyrazole (4)
White-yellowish powder, mp 170–173ꢄC (CH3OH) (Ref. [16] 170–173ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-nitrobenzylidenehydrazino)pyrazole (5)
White powder (96%), mp 284–286ꢄC (C2H5OH) (Ref. [1] 285–286ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-fluorobenzylidenehydrazino)pyrazole (6)
White-yellowish needles (80%), mp 185–187ꢄC (CH3OH) (Ref. [1] 185–186ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-chlorobenzylidenehydrazino)pyrazole (7)
White plates (74%), mp 224–226ꢄC (C2H5OH) (Ref. [1] 230–231ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-trifluoromethylbenzylidenehydrazino)pyrazole (8)
White powder, mp 203–206ꢄC (Ref. [16] 203–206ꢄC).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-bromobenzylidenehydrazino)-pyrazole (9, C14H15BrN4O2)
White powder (71%), mp 177–178ꢄC; 1H NMR (200MHz, CDCl3): ꢂ ¼ 10.16 (bs, –NHpyr), 8.24 (s,
1H, –N¼CH–), 7.71 (d, 2H, J ¼ 8.5 Hz, H-30, H-50), 7.58 (d, 2H, J ¼ 8.5 Hz, H-20, H-60), 4.21 (q, 2H,
J ¼ 7.0 Hz, O–CH2–CH3), 2.29 (s, 3H, –CH3), 1.28 (t, 3H, J ¼ 7.0 Hz, O–CH2–CH3) ppm; 13C NMR
(50 MHz, CDCl3): ꢂ ¼ 163.43 (C¼O), 149.40 (C-3), 147.41 (C-5), 141.22 (–N¼CH–), 134.16 (C-10),
131.47 (C-30, C-50), 128.43 (C-20, C-60), 122.01 (C-40), 92.29 (C-4), 59.02 (O–CH2–CH3), 14.36
(–CH3), 13.59 (O–CH2–CH3) ppm; IR (KBr): ꢃꢀ¼ 3316, 3134, 3095, 3034, 2977, 2929, 1674,

Synthesis and Electrochemical Behavior
743
1610, 1548, 1484, 1347, 1277, 1131, 814, 780, 507cmꢁ1; MS (54 eV): m=z ¼ 352 [(M þ 2)þ, 50%],
350 (Mþ, 49%), 306 [(M þ 2)þ –C2H5OH, 72%], 304 (Mþ –C2H5OH, 63%).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-iodobenzylidenehydrazino)pyrazole (10, C14H15IN4O2)
1
White-yellowish needles (86%), mp 208–210ꢄC (C2H5OH); H NMR (200MHz, CDCl3): ꢂ ¼ 12.40
(bs, –NHpyr), 10.15 (bs, 1H, –NH–N¼), 8.19 (s, 1H, –N¼CH–), 7.75 (d, 2H, J ¼ 8.1 Hz, H-20, H-60),
7.54 (d, 2H, J ¼ 8.0 Hz, H-30, H-50), 4.20 (q, 2H, J ¼ 7.1 Hz, O–CH2–CH3), 2.27 (s, 3H, –CH3), 1.28
(t, 3H, J ¼ 7.1 Hz, O–CH2–CH3) ppm; 13C NMR (50 MHz, CDCl3): ꢂ ¼ 163.58 (–COOC2H5), 148.80
(C-3), 147.17 (C-5), 141.11 (–N¼CH–), 137.28 (C-30, C-50), 134.54 (C-10), 128.40 (C-20, C-60), 95.08
(C-40), 92.03 (C-4), 58.89 (O–CH2–CH3), 14.36 (–CH3), 13.96 (O–CH2–CH3) ppm; IR (KBr):
ꢃꢀ¼ 3290, 3198, 2988, 2973, 2927, 2905, 1660, 1602, 1584, 1546, 1481,1282, 820, 785, 541 cmꢁ1
;
MS (54 eV): m=z ¼ 398 (Mþ, 84%), 352 (Mþ –C2H5OH, 100%).
1H-3-Methyl-4-ethoxycarbonyl-5-(4-methylmercapto-benzylidenehydrazino)pyrazole
(11, C15H18N4O2S)
1
White-yellowish needles (75%), mp 166–167ꢄC (C2H5OH); H NMR (200MHz, CDCl3): ꢂ ¼ 9.40
(bs, –NHpyr), 8.85 (bs, 1H, –NH–N¼), 7.75 (s, 1H, –N¼CH–), 7.49 (d, 2H, H-20, H-60), 7.11 (d, 2H,
H-30, H-50), 4.19 (q, 2H, J ¼ 7.1 Hz, O–CH2–CH3), 2.38 (s, 3H, –CH3), 1.27 (t, 3H, J ¼ 7.1 Hz,
O–CH2–CH3) ppm; 13C NMR (50 MHz, CDCl3): ꢂ ¼ 163.53 (C¼O), 149.52 (C-3), 147.44 (C-5),
142.06 (–N¼CH–), 139.38 (C-40), 131.42 (C-10), 127.02 (C-20, C-60), 125.59 (C-30, C-50), 91.93 (C-4),
58.91 (O–CH2–CH3), 15.06 (SCH3), 14.36 (–CH3), 13.71 (O–CH2–CH3) ppm; IR (KBr): ꢃꢀ¼ 3317,
3206, 3163, 3025, 2982, 2903, 1667, 1609, 1546, 1495, 1278, 1134, 837, 528cmꢁ1; MS (54eV):
m=z ¼ 319 [(M þ 1)þ, 84%], 318 (Mþ, 100%), 272 (Mþ –C2H5OH, 77%).
Electrolysis of 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazole (1) [8]
A solution of 0.02mol ꢂ dmꢁ3 of 1 in DMSO was electrolyzed in a divided cell (diaphragm: glass frit,
porosity G4) using tetra-n-butylammonium tetrafluororborate as supporting electrolyte. The working
electrode consisted of a Pt disc (d ¼ 5 mm), the auxiliary electrode was a Pt wire. The reaction was
conducted at the potential of the first anodic peak of 1 as determined by cyclic voltammetry. The
progress of the electrolysis was followed by recording the decrease of the current with time. The
electrolysis was stopped when the current reached about 20% of its starting value. The crude product
obtained after extraction with diethyl ether and evaporation of the solvent was recrystallized from an
adequate solvent. The resulting product was analyzed by thin layer chromatography, as well as by IR,
1H and 13C NMR spectroscopy and the results were found to be in good agreement with those gathered
for the reference compound 12 obtained as described in Ref. [1].
1H-3-Phenyl-6-methyl-7-(ethoxycarbonyl)pyrazolo[5,1-c][1,2,4]triazole (12)
White-yellowish powder (65%), mp 172–176ꢄC (Ref. [1] 176ꢄC).
Acknowledgements
The authors would like to thank Prof. Dr. A. Merz from the University of Regensburg and Prof.
Dr. G. Fafilek from the Vienna Univ. of Technology for their contribution in acquiring the electro-
chemical data.
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