Polarographic behavior of 4-aryl-2-(1,2-diphenyl-2-oxoethylidenehydrazino)- 4-oxo-2-butenoic acids

Article abstract of DOI:10.1134/S1070363209110140

Polarographic reduction of 4-aryl-2-(1,2-diphenyl-2-oxoethylidenehydrazino) -4-oxo-2-butenoic acids in 2-propanol-water solutions proceeds with the formation of two or three irreversible cathode waves and leads to 4-aryl-2-(1,2-diphenyl-2-hydroxyethylhydr

Full text of DOI:10.1134/S1070363209110140

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 11, pp. 2367–2372. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © G.S. Posyagin, M.A. Vikhareva, O.A. Bystritskaya, A.E. Rubtsov, P.G. Neifeld, V.V. Zalesov, 2009, published in Zhurnal Obshchei
Khimii, 2009, Vol. 79, No. 11, pp. 1845–1850.
Polarographic Behavior of 4-Aryl-2-(1,2-diphenyl-2-
oxoethylidenehydrazino)-4-oxo-2-butenoic Acids
G. S. Posyagin, M. A. Vikhareva, O. A. Bystritskaya,
A. E. Rubtsov, P. G. Neifeld†, and V. V. Zalesov†
Perm State University, Russia, ul. Bukireva 15, Perm, 614990 Russia
e-mail: Alekhsandr.Rubtsov@psu.ru
Received July 7, 2008
Abstract—Polarographic reduction of 4-aryl-2-(1,2-diphenyl-2-oxoethylidenehydrazino)-4-oxo-2-butenoic
acids in 2-propanol–water solutions proceeds with the formation of two or three irreversible cathode waves and
leads to 4-aryl-2-(1,2-diphenyl-2-hydroxyethylhydrazino)-4-hydroxybutanoic acids. The latter suffer hydrolysis
with the rupture of the С2–NH bond and the formation of 4-aryl-2,4-dihydroxybutanoic acids.
DOI: 10.1134/S1070363209110140
In continuation of the previous studies [1] on the
polarographic reduction of derivatives of 4-aryl-2,4-
dioxobutanoic acids we have investigated the
polarographic reduction of 4-aryl-2-(1,2-diphenyl-2-
oxoethylidenehydrazino)-4-oxo-2-butenoic acids (I–V).
Compounds I–V belong to N-substituted α-aminoacids
based on aroylpyruvic acid, that is, are potentially
biologically active compounds. From this point of
view the examination of their polarographic reduction
is not only of theoretical but also of practical interest.
Compounds I–V were first synthesized by the
reaction of 4-aryl-2,4-dioxobutanoic acids with benzil
monohydrazone according to the scheme:
Ph
O
H2NN
4-RC6H4
O
Ph
OH
Ph
O
4-RC6H4
O
N
OH
_H2O
H
N
O
O
Ph
O
I_V
R = Cl (I), Me (II), MeO (III), EtO (IV), H (V).
Their physicochemical properties are presented in
Table 1.
In Table 2 are given the parameters of the polaro-
graphic waves for the studied compounds (values
of E1/2 and id), the limiting current constants Jd =
id c–1 m–2/3 τ–1/6, where с is concentration of depolarizer
with due regard to the effect of dilution with buffer
solutions (0.5 mmol l–1); m is the weight of mercury
dropping in unit time (2.60 mg s–1), τ is the dropping
period (5.40 s).
The polarographic behavior of compounds I–V was
studied in aqueous 2-propanol (25% vol. of i-PrOH) in
the pH range from 3 to 12. In the polarograms we
reliably detect two or three irreversible cathode waves
whose half-wave potentials (E1/2) and limiting currents
(id) depend on the pH of the solution.
Compound I shows three irreversible cathode
waves which manifest themselves in the whole range
of pH from 3 to 12 and which are characterized by a
shift of the half-wave potentials towards more negative
† Deceased.
2367

2368
POSYAGIN et al.
Table 1. Physicochemical properties of compounds I–V
Comp. no.
R
Yield, %
mp, °С
IR spectrum, ν, cm–1
Rf
Cl
79
47
44
41
21
147–148
139–140
168–171
157–159
134–136
3257 (NH), 1705 (COO), 1662 (CO)
3246 (NH), 1700 (COO), 1655 (CO)
3275 (NH), 1700 (COO), 1660 (CO)
3239 (NH), 1665 br (COO, CO)
3258 (NH), 1707 (COO), 1658 (СО)
0.08
0.13
0.07
0.11
0.06
I
Me
MeO
EtO
H
II
III
IV
V
Table 2. Characteristics of polarographic waves for compounds I–V
Compound I
pH
1st wave
2nd wave
3nd wave
a
a
a
–E1/2, V
id, μА
Jd
–E1/2, V
id, μА
Jd
–E1/2, V
id, μА
Jd
3.76
0.50
0.52
0.54
0.65
0.74
0.74
0.78
0.79
0.83
0.85
0.86
0.87
3.00
3.20
3.10
2.34
2.20
2.20
2.10
1.50
0.88
0.66
0.44
0.28
2.40
2.56
2.48
1.87
1.76
1.76
1.68
1.20
0.70
0.53
0.35
0.22
0.82
0.90
0.92
0.98
1.00
1.02
1.06
1.07
1.12
1.14
1.18
1.20
3.90
4.40
3.50
2.50
2.20
1.50
1.90
2.09
2.23
2.29
2.16
2.10
3.12
3.51
2.80
2.00
1.76
1.20
1.52
1.67
1.78
1.83
1.73
1.68
1.30
1.31
1.33
1.34
1.36
1.38
1.47
1.47
1.50
1.55
1.56
1.60
2.90
3.20
3.00
3.40
3.30
1.90
1.30
0.84
0.16
0.86
1.10
2.44
2.32
2.56
2.40
2.72
2.64
1.52
1.04
0.67
0.13
0.69
0.88
1.95
4.68
5.34
6.08
6.77
7.35
8.24
8.94
9.92
10.73
11.63
11.96
pH
Compound II
3.76
4.68
5.34
6.08
6.77
7.35
8.24
8.94
9.92
10.73
11.63
11.96
0.39
0.47
0.51
0.57
0.60
0.64
0.72
0.73
0.73
0.72
0.82
0.86
1.40
1.32
1.72
1.48
1.68
1.68
1.72
1.32
0.88
0.60
0.44
0.34
1.12
1.05
1.37
1.18
1.34
1.34
1.37
1.05
0.70
0.48
0.35
0.27
0.82
0.87
0.93
0.95
0.97
1.01
1.07
1.15
1.20
1.42
1.43
1.43
2.70
3.32
3.28
3.16
2.92
2.56
0.96
0.48
0.88
0.78
0.60
0.72
2.16
2.65
2.62
2.52
2.33
2.04
0.77
0.38
0.70
0.62
0.48
0.58
–
–
–
1.30
1.31
1.32
1.34
–
1.47
1.49
1.55
1.58
1.60
1.64
0.92
1.12
2.08
1.56
–
0.68
0.74
0.80
0.68
0.80
0.64
0.73
0.89
1.66
1.25
–
0.54
0.59
0.64
0.54
0.64
0.51
pH
Compound III
3.76
4.68
5.34
6.08
6.77
7.35
8.24
8.94
9.92
10.73
11.63
11.96
0.36
0.46
0.52
0.58
0.60
0.67
0.73
0.74
0.76
0.78
0.79
0.80
1.28
1.64
1.84
1.56
1.84
1.80
1.88
1.72
0.84
0.60
0.32
0.16
1.02
1.31
1.47
1.25
1.47
1.44
1.50
1.37
0.67
0.48
0.26
0.13
0.76
0.90
1.00
1.06
1.11
1.16
1.23
1.24
1.24
1.25
1.25
1.25
2.28
3.00
3.52
4.28
3.72
2.84
1.96
1.73
2.68
3.04
2.28
2.24
1.82
2.40
2.82
3.42
2.98
2.27
1.57
1.38
2.14
2.43
1.82
1.79
–
–
–
1.33
1.37
1.39
1.40
1.60
1.62
1.63
1.64
1.64
1.65
1.65
1.16
1.12
0.80
0.68
0.44
1.72
1.91
2.16
1.92
1.32
0.80
0.93
0.90
0.64
0.54
0.35
1.38
1.53
1.73
1.54
1.05
0.64
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

POLAROGRAPHIC BEHAVIOR OF 4-ARYL-2-(1,2-DIPHENYL-2-...
2369
Table 2. (Contd.)
Compound IV
pH
1st wave
2nd wave
3nd wave
a
a
a
–E1/2, V
id, μА
Jd
–E1/2, V
id, μА
Jd
–E1/2, V
id, μА
Jd
3.76
4.68
5.34
6.08
6.77
7.35
8.24
8.94
9.92
10.73
11.63
11.96
0.38
0.47
0.50
0.63
0.70
0.72
0.76
0.78
0.80
0.80
0.82
0.83
1.36
1.64
1.40
1.36
1.36
1.26
1.22
1.16
1.12
0.40
0.48
0.16
1.09
1.31
1.12
1.09
1.09
1.01
0.98
0.93
0.90
0.32
0.38
0.13
0.77
0.90
1.00
1.10
1.14
1.17
1.18
1.22
1.24
1.24
1.25
1.26
2.68
3.32
3.40
3.52
3.56
3.12
2.04
1.68
0.76
0.98
2.44
2.48
2.14
2.65
2.72
2.81
2.85
2.50
1.63
1.34
0.61
0.78
1.95
1.98
1.28
1.33
1.36
1.36
1.36
1.38
–
0.92
1.28
0.90
1.04
0.80
0.20
–
0.73
1.02
0.72
0.83
0.64
0.16
–
–
–
–
1.39
1.40
1.59
1.61
1.20
1.27
1.28
1.68
0.96
1.01
1.02
1.34
Compound V
3.76
4.68
5.34
6.08
6.77
7.35
8.24
8.94
9.92
10.73
11.63
11.96
0.24
0.46
0.54
0.56
0.60
0.67
0.70
0.73
0.75
0.78
0.80
0.82
1.00
1.48
1.64
1.64
1.12
1.24
1.23
1.12
0.48
0.40
0.20
0.08
0.80
1.18
1.31
1.31
0.89
0.99
0.98
0.89
0.38
0.32
0.16
0.06
0.70
0.89
0.94
0.99
1.04
1.20
1.21
1.21
1.22
1.23
1.23
1.24
3.56
2.36
1.84
1.64
1.52
1.28
1.24
1.14
0.84
0.88
0.76
0.88
2.85
1.89
1.47
1.31
1.21
1.02
0.99
0.91
0.67
0.70
0.61
0.70
1.27
1.28
1.28
1.29
1.29
1.54
1.55
1.55
1.56
1.57
1.57
1.59
1.60
1.44
1.96
2.00
1.84
1.64
1.76
1.80
2.88
2.24
1.98
1.72
1.28
1.15
1.57
1.60
1.47
1.31
1.41
1.44
2.30
1.79
1.58
1.37
а Jd in µA l s1/2 mol–1 mg–2/3
values with increasing pH. The angular coefficients
dE1/2/dpH of the first wave have different values in
different intervals of pH: at рН 3–5 it is 25 mV/рН
unit, at рН 5–7 it is >100 mV/рН unit, and at pH > 7 it
is 43 mV/рН unit. For the second and the third cathode
waves the dependences of Е1/2 on pH do not vary in the
whole range of pH. For the second wave dE1/2/dpH =
44 mV/рН unit, for the third it is 40 mV/рН unit. The
limiting current for the first wave tends to decrease
with increasing pH, for the second cathode wave the id
has a minimum in the neutral medium, for the third
wave the minimum is reached in alkaline media.
polarographic behavior of the studied compounds are
negligible.
Investigation of the nature of the limiting current
(il) was performed for compounds I and III at three
values of pH of the solution, 3.76, 6.77, and 11.96, and
gave the following results: (1) for compound I for the
first wave in all media and for the second and the third
waves in acidic and neutral media the dependence of il
on concentration (с) is linear, whereas for the latter
two in alkaline media a deviation from the linear
dependence is observed and the values of il become
independent of the concentration of depolarizer when
certain concentrations c are attained; (2) for compound
III the dependence of il on c is linear for the first and
Compounds II–V undergo reduction on a mercury
electrode also in three steps. Certain differences in the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

2370
POSYAGIN et al.
the third waves in all media and for the second wave in
acidic and neutral media, whereas in alkaline media a
deviation of il from linearity is observed for the second
wave, similar to the aforementioned for compound I.
Therefore, the polarographic method can be used for
quantitative determination of the compounds under
consideration in acidic and neutral media.
identified by the methods of TLC, IR and NMR
spectroscopy.
Based on the obtained electrochemical and spectral
data, it is possible to suggest the following mechanism
of reduction of compounds I–V on a mercury
electrode.
First, apparently, the polarographic reduction of the
С2=С3 double bond occurs with consumption of two
electrons and two protons and the formation of 4-aryl-
2-(1,2-diphenyl-2-oxoethylidenehydrazino)-4-oxobuta-
noic acids (intermediate A1). This process corresponds
to the first two-electron cathode wave. Apparently, A1
is reduced also with the consumption of two electrons
and two protons and the formation of 4-aryl-2-(1,2-
The shape of the dependence of the limiting current
on the height of mercury column and the temperature
allows a conclusion that for compounds I and III in
acidic and neutral media it is a diffusion-controlled
limiting current. However, in an alkaline medium the
limiting current for the second and the third waves for
compound I and that for the second wave for
compound III have an adsorption character.
diphenyl-2-oxoethylhydrazino)-4-oxobutanoic
acids
To elucidate the mechanism of reduction of the
studied compounds on a mercury electrode we have
determined the number of electrons (n) consumed by
the molecule of depolarizer (compound III) upon
reduction in neutral medium (рН 8.24). Using the
method of electrolysis at the controlled potential of the
working electrode (CPE) corresponding to the plateau
of the limiting current for each of the waves, the
following data have been obtained: for Е = –0.97 V,
n = 2.12; Е = –1.41 V, n = 4.21, Е = –1.83 V, n = 8.22.
The products of electrolysis were isolated and
(intermediate A2). This process corresponds to the
second two-electron cathode wave. In intermediate A2,
two similar in nature carbonyl groups are present,
which, most probably, are involved in intramolecular
hydrogen bonds. Due to the similarity of their
properties both carbonyl groups are probably reduced
simultaneously with the consumption of four electrons
and four protons to form eventually 4-aryl-2-(1,2-
diphenyl-2-hydroxyethylhydrazino)-4-hydroxybutanoic
acids (VI). This process corresponds to the third four-
electron cathode wave.
O
O
Ar
Ar
OH
OH
2 H+, 2e_
Ph
Ph
O
N
O
N
H
N
H
N
Ph
Ph
O
O
I_V
A1
O
Ar
O
OH
Ph
_
2 H+, 2e_
4 H+, 4e
Ar
O
N
OH
Ph
H
N
OH NH
Ph
Ph
H
N
O
H
OH
A2
VI
O
Ph
H2O
Ar
+
NH2NH
OH
Ph
OH OH
HO
VIII
VII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

POLAROGRAPHIC BEHAVIOR OF 4-ARYL-2-(1,2-DIPHENYL-2-...
2371
1
Judged from the Н NMR spectrum recorded in a
solution in two forms, the Z-enehydrazine and β-
polar solvent, DMSO-d6, compound III exists in
ketohydrazone.
O
O
4-MeOC6H4
OH
4-MeOC6H4
OH
Ph
Ph
O
N
O
N
H
N
N
Ph
Ph
O
O
The Z-enehydrazine form of compound III is
characterized by the following signals in the proton
spectrum: a singlet of three protons of the methoxy
group at 3.76 ppm, a singlet of the vinyl proton at
6.36 ppm, a singlet of the NH group involved in the
intramolecular hydrogen bond at 12.71 ppm. In the
spectrum is also observed a multiplet of aromatic
protons centered at 7.55 ppm.
the methoxy group at 4.27 ppm, a doublet of doublets
of the methine proton of the C2H group at 4.15 ppm, a
doublet of the С2Н methine proton of the ethyl group
at the nitrogen atom at 3.84 ppm (J = 9.3 Hz), four
broadened singlets of the NH and OH groups at 2.98,
3.10, 3.63, 3.79 ppm, and a complex multiplet of the
СН2 group at 2.2–2.4 ppm are observed. The signal of
the carboxyl group could not be detected in the
spectrum, apparently due to its strong broadening.
The β-ketohydrazone form is characterized by a
singlet of protons of the methoxy group at 3.81 ppm
and a singlet of protons of the methylene group at
4.49 ppm.
Compound VI is the final product of the elec-
trolysis, although we failed to isolate it intact from the
solution. Its formation, however, is corroborated by the
fact that 2,4-dihydroxy-4-(4-methoxyphenyl)butanoic
acid (VII) was identified as the product of electrolysis
of compound III.
According to the integral intensity of the signals in
the 1Н NMR spectrum, the Z-enehydrazine form
dominates and the ratio of the forms is 9:1.
The formation of compound VII is quite possible to
occur in the process of isolation as a result of
hydrolysis of compound VI with the rupture of the С2–
NH bond. A structurally close to compound VII ethyl
2-hydroxy-4-phenylbutanoate was obtained earlier also
by stepwise reduction of ethyl 2,4-dioxo-4-phenyl-
butanoate over palladium catalysts [2].
Since the polarographic reduction of compounds I–
V also was studied in a polar medium it is presumable
that just the Z-enehydrazine form undergoes the
reduction.
1Н NMR spectra recorded from the products of
electrolysis of compound III carried out at рН = 8.24,
Е = –0.97 V, and рН = 8.24, Е = –1.41 V, have
complex character and contain a set of signals from the
mixture of the products of electrolysis and the starting
compound (the Z-enehydrazine form is registered in
the spectra).
EXPERIMENTAL
IR spectra were recorded on a FSM–1201 instru-
1
ment in mineral oil. H NMR spectra were registered
on a Mercury plus 300 spectrometer in CDCl3 or
In the 1Н NMR spectrum recorded from the product
of electrolysis carried out at рН = 8.24 and Е =
–1.83 V the signals of the starting compound III are
absent and the signals of 2-[N2-(1,2-diphenyl-2-hyd-
roxy)ethyl]hydrazino-4-hydroxy-4-(4-methoxyphenyl)-
butanoic acid (VI) are present. In the spectrum apart
from the multiplet of aromatic protons centered at
7.48 ppm a triplet of the methine proton of the С4Н
group at 4.31 ppm (J = 6.9 Hz), a doublet of the С2Н
methine proton of the ethyl group at the oxygen atom
at 4.28 ppm (J = 9.3 Hz), a singlet of three protons of
DMSO-d6 with HMDS as an internal reference.
Polarographic measurements were performed in
25% aqueous 2-propanol in the range of pH from 3 to
12. The Britton-Robinson buffer solutions were used to
keep a constant pH. Polarograms were recorded on a
PU-1 polarograph in a three-electrode cell by means of
classical polarography.
To determine the number of electrons consumed by
the molecule of the depolarizer the CPE was per-
formed in a YaCE cell with separated cathode and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009

2372
POSYAGIN et al.
anode spaces, with platinum wire anode, mercury
cathode at the bottom, and a saturated silver chloride
reference electrode. The cathode potential was kept
constant by means of a P–5848 potentiostat. The amount
of electricity passed was determined by an IPT-1 constant
current integrator. CPE, as well as all polarographic
measurements, were performed in a buffer solution in
25% aqueous 2-propanol at рН 8.24. The products of
electrolysis were extracted with chloroform.
2,4-Dihydroxy-4-(4-methoxyphenyl)butanoic
acid (VII). 2-Propanol–water solution after preparative
electrolysis of compound III at рН 8.24 and Е =
–1.83 V was twice extracted with equal volume of
CHCl3 and the combined chloroform extracts were
evaporated. The oily residue was refluxed in ethanol
with charcoal. After filtration and removal of solvent
an oily substance was obtained. According to TLC it
was an individual compound with Rf 0.99. 1Н NMR, δ,
ppm: 2.21 m (2Н, СН2), 3.85 t (1Н, С2Н), 3.95 s (3Н,
СН3), 4.09 t (1Н, С4Н), 4.26 s (1Н, ОН) 4.70 s (1Н,
ОН), 7.11 d (2Н, С6Н4), 7.54 d (2Н, С6Н4).
Thin layer chromatography was performed on
standard Silufol UV-245 plates in the system of
solvents ether–benzene–acetone (10:9:1) after 10 cm
run of the solvent front. The spots were visualized by
iodine vapor.
ACKNOWLEDGMENTS
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 08-03-
00488а).
2-(1,2-Diphenyl-2-oxoethylidenehydrazino)-4-oxo-
4-(4-chlorophenyl)-2-butenoic acid (I). To the solu-
tion of 2.26 g (0.1 mol) of 2-hydroxy-4-oxo-4-(4-
chlorophenyl)-2-butenoic acid in 20 ml of ethanol the
solution of 2.24 g (0.1 mol) of benzil monohydrazone
in 20 ml of ethanol was added, the mixture was kept at
20–25оС for 24 h, cooled to 0оС, the precipitate
formed was filtered off, crystallized from acetonitrile.
Yield 3.4 g (79%), mp 147–148оС. Compounds II–V
were prepared similarly.
REFERENCES
1. Posyagin, G.S., Posyagina, E.Yu., Zalesov, V.V., and
Kataev, S.S., Russ. J. Gen. Chem., 2001, vol. 71, no. 10,
p. 1574.
2. Slavinska, V., Sile, Dz., Rozenthal, G., Maurops, G.,
Popelis, J., Katkevich, M., Stonkus, V., and Lukevics, E.,
Chem. Heterocycl. Comp., 2006, vol. 42, no. 5, p. 570.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 11 2009