Kinetics of hydrolysis of five-membered C-nitroheterocycles: Pyrazole, imidazole, 1,2,4-triazole, and isoxazole derivatives

Article abstract of DOI:10.1007/s11172-006-0195-1

Alkaline hydrolysis of mono-and dinitro derivatives of five-membered heterocycles, viz., pyrazole, imidazole, 1,2,4-triazole, and isoxazole, is accompanied by the elimination of the nitro group in the form of a nitrite anion. The hydrolysis kinetics was studied by the polarographic and photometric methods. The experimentally determined hydrolysis rate constants depend on the nature of the heterocycle. A possible mechanism for hydrolytic transformations of the compounds under study was proposed on the basis of the calculated thermodynamic parameters of the reaction (Δ G ^≠, ΔH ^≠, ΔS ^≠).

Full text of DOI:10.1007/s11172-006-0195-1

Russian Chemical Bulletin, International Edition, Vol. 54, No. 12, pp. 2813—2819, December, 2005
2813
Kinetics of hydrolysis of fiveꢀmembered Cꢀnitroheterocycles: pyrazole,
imidazole, 1,2,4ꢀtriazole, and isoxazole derivatives
L. A. Trukhacheva,a V. I. Levina,b N. B. Grigor´ev,b A. P. Arzamastsev,a I. L. Dalinger,c I. A. Vatsadze,c
G. P. Popova,c S. A. Shevelev,c and V. G. Granikb
ꢀ
aI. M. Sechenov Moscow State Medical Academy,
13 Nikitsky bul´v., 121019 Moscow, Russian Federation.
bState Scientific Center of Antibiotics,
3a ul. Nagatinskaya, 117105 Moscow, Russian Federation.
Eꢀmail: vggranik@mail.ru
cN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328
Alkaline hydrolysis of monoꢀ and dinitro derivatives of fiveꢀmembered heterocycles, viz.,
pyrazole, imidazole, 1,2,4ꢀtriazole, and isoxazole, is accompanied by the elimination of the
nitro group in the form of a nitrite anion. The hydrolysis kinetics was studied by the polaroꢀ
graphic and photometric methods. The experimentally determined hydrolysis rate constants
depend on the nature of the heterocycle. A possible mechanism for hydrolytic transformations
of the compounds under study was proposed on the basis of the calculated thermodynamic
parameters of the reaction (∆G≠, ∆H≠, ∆S≠).
Key words: Cꢀnitro derivatives of fiveꢀmembered heterocycles, pyrazole, imidazole,
isoxazole, nitrite anion, NOꢀdonor activity, xanthine oxidase, free activation energy, activaꢀ
tion entropy, activation enthalpy, Gibbs energy.
Some nitro compounds1—3 are exogenic generators of
nitrogen oxide. The activity of Oꢀnitro (nitroesters1) and
Nꢀnitro compounds (in particular, Nꢀnitropyrazoles4) in
the formation of NO is well known. Many aliphatic Cꢀnitro
derivatives can also evolve NO under hydrolytic condiꢀ
tions.1 In addition, it is known that some Cꢀnitroꢀ
heterocycles, such as medicines of the nitrofuran5,6 and
nitroimidazole7,8 series, can exhibit the NOꢀdonor activꢀ
ity. However, no systematic studies in the area of Cꢀnitro
compounds functioning as nitrogen oxide donors were
performed.
nitro groups in the heterocycle structure on the efficiency
–
of elimination of the nitro group in the form of NO2
.
Results and Discussion
Compounds 1—15 were synthesized according to
Scheme 1.
Acid chlorides (see Scheme 1) were synthesized by
reflux of the corresponding compounds 17а—c 11 and
17d 12 in excess SOCl2 and further used without addiꢀ
tional purification. The nitration of 5ꢀmethylꢀ3ꢀisoxazoleꢀ
carboxylic acid (18) with sodium nitrate in H2SO4 afꢀ
forded nitro acid 17е (Scheme 2). 1ꢀ(pꢀMethoxypheꢀ
nyl)carbamidomethylꢀ3,4ꢀdinitroꢀ5ꢀmethoxypyrazole
(10) has been described elsewhere.13
Acid 17е * decomposes gradually on storage and,
hence, it was converted into acid chloride. The latter was
used to synthesize amide 15 without additional purifiꢀ
cation.
When studying the alkaline hydrolysis of synthesized
compounds 1—16, the formation of the nitrite anion was
found, which is one of markers of nitrogen oxide formaꢀ
tion and whose yield depends strongly on the heterocycle
nature (Table 1).
In the present work, we studied Cꢀnitro derivatives of
pyrazole, imidazole, 1,2,4ꢀtriazole, and isoxazole (1—16)
as potential NO donors.
It is known that one of the routes for synthesis of
nitrogen oxide in the organism is the nitriteꢀnitrateꢀ
xanthine oxidase method. Xanthine oxidase is capable of
catalyzing NO generation under anaerobic conditions,
using nitrite ions as the substrate.9 In a recent publicaꢀ
tion10 the problem of heterocyclic ring opening under
hydrolytic conditions is considered. It was indicated that
these processes can occur via both the nonꢀenzymatic
mechanism and enzymatic catalysis. It seemed of interest
to study the ability of these compounds to generate a
nitrite ion under alkaline hydrolysis conditions and to
reveal the effect of the heterocycle nature and number of
* 1H NMR data (δ, DMSOꢀd6): 2.3 (s, 3 H).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2719—2725, December, 2005.
1066ꢀ5285/05/5412ꢀ2813 © 2005 Springer Science+Business Media, Inc.

2814
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Trukhacheva et al.
In principle, two main routes of nitrite anion eliminaꢀ
tion are possible under these conditions. The first route is
ipsoꢀsubstitution characterized by the formation of the
corresponding σꢀcomplex followed by the elimination of
the NO2 anion. The second route includes the prelimiꢀ
nary heterocycle opening and dearomatization of the sysꢀ
tem followed by the liberation of the nitrite anion from
the nonꢀheterocyclic precursor.
To compare activities of compounds 1—16 as potenꢀ
tial NOꢀdonors, let us compare the aromaticity paramꢀ
eters of the basic heterocycles, whose derivatives are studꢀ
ied in the present work.
–

Hydrolysis of fiveꢀmembered nitroheterocycles
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005 2815
Scheme 1
Scheme 2
According to calculations, isoxazole is least aromatic
among other fiveꢀmembered heterocycles.14 The mechaꢀ
nism of isoxazole opening under the action of alkali was
studied in detail,15 and the order of decreasing aromaticꢀ
ity is as follows: benzene > 1,2,4ꢀtriazole > pyrazole >
> imidazole > isoxazole.16
R =
(17a),
(17b),
(17c),
(17d)
On heating solutions of mononitro derivatives of
1,2,4ꢀtriazole 1—5 in 0.1 M NaOH containing 10% ethaꢀ
Table 1. Yield of the nitrite anion due to hydrolytic transformations of amides 1—16 in a 10% aqueousꢀ
alcohol solution of 0.1 M NaOH
Amide
T/°C
t/min
Yield (%)
Amide
T/°C
t/min
Yield (%)
1
40
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
0
0
0.8
2.1
0
0
0.9
1
9
40
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
60
120
6.7
10
70
40
70
40
70
40
70
40
70
40
70
40
70
40
70
70
40
70
40
70
40
70
40
70
40
70
40
70
40
70
18.6
28.1
6.5
10.4
19
27.3
7
12
2
3
4
5
6
7
8
10
11
12
13
14
15
16
0
1.2
2.9
3.5
1
1.3
2
3.2
0.5
1.2
2.3
2.9
0
17.9
27
0
0
0.7
1.0
0
0.1
0.6
1.32
0
0.5
1.2
2
5
7
9
16
103*
108*
125*
130*
0
0.8
0.9
0
0
1.3
1.5
0
0
0.8
1.3
* The yield of the nitrite anion more than 100% in the case of the dinitroimidazole derivative is a conseꢀ
quence, probably, of the quantitative elimination of the first nitro group and the onset of consumption of the
second group.

2816
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Trukhacheva et al.
Table 2. Rate constants (kav) at different temperatures for derivatives of dinitropyrazole 10, isoxazole 15, and dinitroimidazole 16
Comꢀ
pound
kav/s–1 at temperature/°C
25
35
40
50
70
10
15
16
—
4.4•10–5 2.6•10–6
—
2.3•10–3 3.1•10–4
9.4•10–5 8.5•10–6
9.3•10–5 1.1•10–6
5.0•10–3 5.0•10–4
3.5•10–4 3.5•10–5
—
3.1•10–5 4.6•10–6
—
3.1•10–5 4.6•10–6
—
3.9•10–4 6.2•10–5
—
Table 3. Free energy (∆G≠), enthalpy (∆H≠), and free enꢀ
tropy (∆S≠) of activation of the hydrolytic cleavage of comꢀ
pounds 10, 15, and 16
nol at 70 °C for 180 min, the isolation of the nitrite anion
depends weakly on the basic heterocycle. For derivatives
of nitropyrazole 6—8 and nitroimidazole 12—14, the yield
–
of NO2 is ∼2%, while its yield for nitrotriazole is someꢀ
Comꢀ
pound
∆G≠
∆H≠
–∆S≠
/cal mol–1 K–1
what higher (∼3%). Storage of nitroisoxazole derivative
15 under these conditions leads to a considerable degraꢀ
kcal mol–1
–
dation of the starting molecule, and NO2 is formed in
10
15
16
24.1 3.0
24.4 2.5
13.2 1.2
26.8 2.7
11.1 1.5
12.1 1.2
8.6 0.3
41.8 1.2
30.2 1.5
16% yield.
Under similar conditions, the isoxazole cycle cleavage
proceeds15 via Scheme 3.
tive activation entropy indicates the formation of a highly
ordered transition state.17
Scheme 3
The general presumable scheme of elimination of the
–
nitro group in the form of NO2 on heating of derivative
15 in the presence of alkali can be presented as Scheme 4.
Evidently, the intensity of interaction with nucleoꢀ
philic reagents should increase sharply with an increase in
the number of electronꢀwithdrawing groups in the heteroꢀ
cycle. On going from monoꢀ to dinitro derivatives, nitrite
anion elimination due to the nucleophilic attack becomes
much more probable.
In the present work, we studied the degradation of
Nꢀ(3,4ꢀdimethoxyphenyl)carbamoylꢀ4ꢀnitroꢀ5ꢀmethylꢀ
isoxazole (15). The rate constants were determined under
assumption that the process is a pseudoꢀmonomolecular
reaction (since the main reagent, viz., alkali, is taken in a
high excess). Although the degree of decomposition of
compound 15 with nitrite anion elimination is relatively
high, on a fairly long heating in a great excess of alkali the
degradation of this isoxazole derivative can also occur in
other directions. This uncertainty decreases the accuracy
of determination of reaction rate constants and, hence,
thermodynamic parameters. It was found that the differꢀ
ences in the kinetic parameters (reaction rate constants)
exceed 10%, and the average constant values (kav), availꢀ
able from the spectrophotometric and polarographic meaꢀ
surements, were used for further calculations.
The reaction rate constants obtained by the study of
the alkaline degradation of compound 10 are given in
Table 2. The thermodynamic parameters of the process
calculated from these data are presented in Table 3. The
amount of the nitrite ion reaches 27%, which is much
higher than that for the mononitro derivatives. In this
case, a rather high activation enthalpy indicates a probꢀ
able bond cleavage in the transition state. A comparatively
low negative activation entropy indicates that the bond is
almost cleaved and the transition state is similar to the
final structure (Scheme 5). Due to this, the entropy value
of the transition state is similar to that of the initial state.
The behavior of 1ꢀmethylꢀ4,5ꢀdinitroimidazole (16)
differs so strongly from that of pyrazole derivative 10 that
this cannot be explained by the difference in the nature of
substituents in position 1. For example, compound 16
exhibits the fast (within approximately 12 min at 50 °C)
and qualitative elimination of the nitrite anion. In addiꢀ
tion, the next step of interaction is a much slower process:
degradation of the intermediate that formed with withꢀ
drawal of one more nitro group as the second nitrite anion.
In this case, the reaction mechanism differs from the
mechanism of degradation of pyrazole derivative 10. For
compound 16, the activation enthalpy is much lower,
We attempted to use the kav values to analyze a posꢀ
–
sible mechanism of NO2 elimination. The kav values
obtained at different temperatures for compounds 10, 15,
and 16 are given in Table 2. The thermodynamic paramꢀ
eters calculated from these data are presented in Table 3.
A relatively low free activation enthalpy can be attribꢀ
uted to a small energy consumption needed to cleave the
N—O bond and open the isoxazole cycle, which posꢀ
sesses, as already mentioned, the lowest aromaticity in
the series of fiveꢀmembered heterocycles. The high negaꢀ

Hydrolysis of fiveꢀmembered nitroheterocycles
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005 2817
Scheme 4
TS is transition state
–
Scheme 5
occurs in the rateꢀdetermining step of the process of NO2
group elimination. Similar reactions of imidazole cycle
opening under hydrolytic and other conditions with elimiꢀ
nation of nitrogen oxide in the form of the nitrite anion
are described in literature.1—3
It should be mentioned in conclusion that the aboveꢀ
presented schemes require additional proves and should
be considered presently as presumable. The main result of
the present work is the reliably determined experimental
fact that the studied Cꢀnitroꢀ and especially dinitroazole
derivatives can eliminate the nitrite anion. A possibility of
its elimination is determined by the structural features
and stability of these derivatives under the conditions of
nucleophilic attack.
R = pꢀMeOC6H4NHCOCH2
while the activation entropy is expressed by a considerꢀ
able negative value as for mononitroisoxazole derivaꢀ
tive 15. The imidazole cycle is much less aromatic than
the triazole and pyrazole cycles. The results obtained for
compound 16 can be interpreted on the basis of the folꢀ
lowing assumption. Under the conditions of attack of the
hydroxyl anion, the primary step of imidazole cycle degꢀ
radation is imidazole ring opening (Scheme 6), which
The process of nitrite anion elimination was studied
on heating in alkali, i.e., under the conditions far from
physicological. In many cases it remains unknown how
the hydrolysis of heterocycles occurs in the organism.
However, for thiazolidine derivatives, the cycle cleavage
is known to be catalyzed by enzyme 5ꢀoxoꢀLꢀprolinase.
Our experiments represent a model process conducted
under nonꢀphysicological conditions. However, it cannot
Scheme 6
TS is transition state

2818
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005
Trukhacheva et al.
30 min to a solution of 5ꢀmethylꢀ3ꢀisoxazolecarboxylic acid
(Acros, 7.0 g, 0.055 mol) in concentrated H2SO4 (100 mL). The
reaction mixture was stored for 8 h at 50 °C, then poured into ice
(400 g), extracted with ether (2×100 mL), and dried with MgSO4.
The solvent was removed in vacuo, and the residue was crystalꢀ
lized from 1,2ꢀdichloroethane. The yield was 7.5 g (79%).
Synthesis of amides 1—15 (general procedure). A solution of
acid (0.001 mol) in SOCl2 (10 mL) was refluxed for 4 h, an excess
of SOCl2 was evaporated, and a solution of amine (0.001 mol) in
MeCN (10 mL) was added. The mixture was heated to boiling
and left to stand for 16 h. The resulting mixture was diluted with
water (20 mL), and the precipitate that formed was filtered off,
washed with 10% NH3 and water, and dried in air.
be excluded that that the compounds under study can be
sources of NO in the organism as well, because the rates
of the processes and yields of final products increase mulꢀ
tiply under enzymatic catalysis conditions. The fact of
determination of significant amounts of the nitrite anion
during degradation of fiveꢀmembered nitroheterocycles
suggests substantially that these compounds can be genꢀ
erators of nitrogen oxide in the living organism as well.
From this point of view, it is important that the comꢀ
pounds of the type under study and their analogs can
liberate the nitrite anion and are of significant interest
due to their biological activity.
In all cases, the yields of amides were 90—95%. The melting
points and 1H NMR and elemental analysis data for the syntheꢀ
sized compounds are collected in Table 4.
Experimental
The kinetic parameters were measured by the photocoloriꢀ
metric and polarographic methods.
1
H NMR spectra were recorded on a Bruker ACꢀ300 instruꢀ
ment. Chemical shifts are presented relative to Me4Si. The course
of the reaction and purity of substances were monitored by TLC
on Silufol UVꢀ254 plates.
5ꢀMethylꢀ4ꢀnitroꢀ3ꢀisoxazolecarboxylic acid (17е). Sodium
nitrate (7.1 g) was added with stirring at room temperature for
The solutions under study with a concentration of
10–4—10–3 mol L–1 in the presence of an 0.1 M solution of
NaOH and 10% alcohol were maintained for 3—4 h at three
temperatures: 23, 40, and 70 °C. Samples for photocolorimetric
and polarographic studies were taken at certain time intervals
Table 4. Physicochemical properties of compounds 1—15
Comꢀ
pound
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR data
(DMSOꢀd6, δ)
(%)
H
C
N
1
188
135
195
147
126
177
60
50.82
50.57
45.17
45.29
46.86
46.91
52.34
52.36
47.47
47.66
57.03
56.93
58.25
58.31
53.89
53.79
48.94
48.91
47.01
46.57
45.77
46.03
57.04
56.93
58.08
58.33
52.45
52.50
51.99
52.34
4.08
4.24
2.83
3.04
4.29
4.26
4.66
4.76
4.08
4.00
5.10
5.14
5.51
5.60
4.82
4.86
4.00
4.10
3.91
3.87
3.94
4.14
5.14
5.05
5.54
5.59
5.16
5.04
4.26
4.71
26.81
26.81
26.07
26.41
22.38
22.79
25.63
25.44
24.56
26.26
20.07
20.43
19.50
19.44
19.11
19.30
22.12
21.93
21.04
20.89
18.97
19.17
20.11
20.43
19.64
19.43
17.47
17.49
13.47
13.08
С11Н11N5O3
2.3 (s, 3 Н); 5.3 (s, 2 Н); 7.2, 7.5 (both d, 2 H each);
8.9. 10.4 (both s, 1 H each)
5.3 (s, 2 Н); 7.2 (m, 3 Н); 7.9 (m, 1 Н);
8.9, 10.4 (both s, 1 H each)
3.7 (s, 6 Н); 5.3 (s, 2 Н); 6.9, (both d, 2 H each);
7.3, 8.9, 10.4 (all s, 1 H each)
1.2 (t, 3 Н); 2.6 (q, 2 Н); 5.3 (s, 2 Н);
7.2, 7.5 (both d, 2 H each); 8.9, 10.4 (both s, 1 H each)
3.8 (s, 3 Н); 5.3 (s, 2 Н); 6.9, 7.5 (both d, 2 H each);
8.9, 10.4 (both s, 1 H each)
2.2, 2.3 (both s, 3 H each); 5.1 (s, 2 Н); 6.9 (s, 1 Н);
7.2, 7.5 (both d, 2 H each); 10.3 (s, 1 Н)
1.2 (t, 3 Н); 2.3 (s, 3 Н); 2.6 (q, 2 Н); 5.1 (s, 2 Н);
6.9 (s, 1 Н); 7.2, 7.5 (both d, 2 H each); 10.3 (s, 1 Н)
2.3 (s, 3 Н); 5.1 (s, 2 Н); 6.9 (d, 3 Н); 6.9 (s, 1 Н);
7.5 (d, 2 Н); 10.3 (s, 1 Н)
2.3, 2.7 (both s, 3 H each); 5.2 (s, 2 Н); 7.2 (d, 2 Н);
7.5 (d, 2 Н); 10.3 (s, 1 Н)
2.6 (s, 3 Н); 5.2 (s, 2 Н); 6.9, 7.5 (both d, 2 H each);
10.2 (s, 1 Н)
2.6 (s, 3 Н); 3.7 (s, 6 Н); 5.3 (s, 2 Н); 6.9, 7.1
(both d, 1 H each); 7.3 (d, 2 Н); 10.3 (s, 1 Н)
2.2, 2.3 (both s, 3 H each); 5.0 (s, 2 Н); 7.1, 7.5
(both d, 2 H each); 8.3, 10.3 (both s, 1 H each)
1.2 (t, 3 Н); 2.6 (q, 2 Н); 5.0 (s, 2 Н); 7.2 (d, 2 Н);
7.5 (d, 2 Н); 8.3, 10.3 (both s, 1 H each)
2.3 (s, 3 Н); 3.7 (s, 6 Н); 5.0 (s, 2 Н); 6.9, 7.1
(both d, 1 H each); 7.3, 8.3, 10.3 (all s, 1 H each)
2.9 (s, 3 Н); 3.8 (s, 6 Н); 7.0, 7.2 (both d, 1 H each);
7.3, 11.0 (both s, 1 H each)
2
C10H8FN5O3
C12H13N5O5
C12H13N5O3
C11H11N5O4
C13H14N4O3
C14H16N4O5
C13H14N4O4
C13H13N5O5
C13H13N5O6
C14H15N5O7
C13H14N5O4
C14H16N4O3
C14H16N4O5
C14H15N3O6
3
4
5
6
7
8
186
209
172
174
251
250
250
205
9
10
11
12
13
14
15

Hydrolysis of fiveꢀmembered nitroheterocycles
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 12, December, 2005 2819
(at first, at an interval of 10 min and then every half an hour).
Three or more entries were carried out at each temperature.
The Griess procedure18 was used for the photocolorimetric
determination of the yield of the nitrite anion: formation of a
colored azo dye due to diazotization followed by azocoupling.
A 2% solution of sulfanilic acid in 1 M HCl was used as a diazo
component, and an 0.3% aqueous solution of αꢀnaphthylꢀ
ethylenediamine hydrochloride served as an azo component.
The absorbance of colored solutions was determined on a
KFKꢀ3ꢀ01 photoelectrocolorimeter, which makes it possible to
measure the absorbance in the wavelength interval from 200 to
900 nm. Cells with an optical path length of 1 cm were used. The
absorption maximum of colored solutions was detected at
542 nm. The yield of nitrite in percentage was calculated from
the ratio of the absorbance of solutions under study to the absorꢀ
bance of the series of solutions of sodium nitrite with a specified
concentration.
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Harrison, Biochem. Biophys. Res. Commun., 2000, 270, 880.
10. B. Testa and J. M. Mayer, Hydrolysis in Drug and Prodrug
Metabolism, Chemistry, Biochemistry, and Enzymology, Wileyꢀ
VCH, Zurich, Switzerland, 2003, p. 710.
Polarographic studies were carried out on a dropping merꢀ
cury electrode with the parameters τ = 2.2 s, m = 1 mg s–1 via
the threeꢀelectrode scheme on a PUꢀ1 polarograph (Belarus)
in the dc and differentialꢀimpulse polarographic mode. An
XY Recoder 4103 twoꢀcoordinate recorder (Czechia) was used
to detect polarograms. A saturated calomel electrode served as
reference. Measurements were conducted in a temperatureꢀconꢀ
trolled cell at 25—50 °C. Before polarogram recording, air oxyꢀ
gen was preliminarily removed from solutions in the cell by
purging with an inert gas (argon).
–
The yield of NO2 during hydrolysis of the compounds unꢀ
der study was determined by a decrease of the fourꢀelectron
reduction wave of the nitro group in time.
Once a linear dependence of the wave height (H ) on the
working solution (C) (polarographic method) or that of the abꢀ
sorbance (А) on C (spectrophotometric method) was established
for a concentration interval of 10–5—10–3 mol L–1, the hydrolyꢀ
sis rate constants were calculated as for a quasiꢀmonomolecular
reaction of the first order, because alkali for hydrolysis is taken
in an amount by two—three orders greater than the amount of
the compound under study.
The reaction rate constants were determined by the graphiꢀ
cal method from a slope of the plot –lnHlim/H (or –lnAlim/A)
vs. t (H is the height of the polarographic wave, А is the absorꢀ
bance, and t is time/min). The experimental values correspondꢀ
ing to the initial linear regions of the kinetic curves were taken
into account in calculations (in a time interval of 10—60 min).
The activation enthalpy and entropy values were calculated
by the formulas19:
11. B. Xuan, T. Wang, G. Cy. Chiou, I. L. Dalinger, T. K.
Shkineva, and S. A. Shevelev, Acta Pharmacol. Sin., 2002,
23, 705.
12. R. M. Kochugin, E. V. Aleksandrova, V. S. Korsunskii, and
V. S. Shmekhunova, Khim. Geterotsikl. Soedin., 2000, 36,
178 [Chem. Heterocycl. Compd., 2000, 36 (Engl. Transl.)].
13. S. S. Novikov, A. I. Khmel´nitskii, T. S. Novikova, O. V.
Lebedev, and A. V. Emishina, Khim. Geterotsikl. Soedin.,
1970, 5, 669 [Chem. Heterocycl. Compd., 1970 (Engl.
Transl.)].
14. Comprehensive Heterocyclic Chemistry, Ed. A. R. Katritsky,
Pergamon Press, Oxford—New York—Toronto—Sidney,
Paris—Frankfurt, 1984, Vol. 6, p. 3.
15. A. Munno, V. Bertini, and F. Lucchesini, J. Chem. Soc.,
Perkin Trans. 2, 1977, 1121.
∆H≠ = ∆G≠ – RT,
∆S≠ = [lnk – ln(kT/h) + (E – RT )/(RT )]R,
16. A. F. Pozharskii, Teoreticheskie osnovy khimii geterotsiklov
[Theoretical Foundations of Chemistry of Heterocycles],
Khimiya, Moscow, 1985, 287 pp. (in Russian).
17. G. Becker, Einfuhrung in die Electronen Theorie Organischꢀ
Chemischer Reaktionen, Ferlag der Wissenschaften, Berlin,
1974, 653.
18. J. P. Griess, Ber. Deutsch Chem. Ges., 1879, 12, 426.
19. N. M. Emmanuel´ and D. G. Knorre, Kurs khimicheskoi
kinetiki [The Course of Chemical Kinetics], Vysshaya Shkola,
Moscow, 1974, 400 pp. (in Russian).
where ∆H≠ is the free activation enthalpy (kcal mol–1), ∆G≠ is
the free activation energy (kcal mol–1), ∆S≠ is the free activation
entropy (cal mol–1 K–1), E is the activation energy (kcal mol–1),
k is Boltzmann constant (0.33•10–23 cal K–1), T is the absolute
temperature (K), k is the rate constant (s–1), h is Planck´s
constant (13.744•10–34 cal s), and R is the gas constant
(2.02 cal mol–1 K–1).
The average values of the rate constants obtained after
three—four entries at each temperature were used in calculaꢀ
tions. The relative errors, being 10% on the average, were
calculated for each value.
Received January 19, 2005;
in revised December 7, 2005