Thermodynamic and kinetic aspects of a single-reactor synthesis of 5-amino-3-methyl-1,2,4-triazole hydrochloride from aminoguanidine and acetic acid

Article abstract of DOI:10.1134/S1070427211030116

Fundamental thermodynamic and kinetic aspects of the reaction in which acetic acid guanyl hydrazide is formed from aminoguanidine and acetic acid in aqueous solutions at pH 0.6-1.5 and the kinetics of cyclization of acetic acid guanyl hydrazide hydrochloride to 5-amino-3-methyl-1,2,4-triazole hydrochloride in a melt were studied. Methods for synthesis of acetic acid guanyl hydrazide hydrochlorides and 5-amino-3-methyl-1,2,4-triazole hydrochloride were developed.

Full text of DOI:10.1134/S1070427211030116

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2011, Vol. 84, No. 3, pp. 400–406. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © E.V. Tarasova, V.M. Chernyshev, A.V. Chernysheva, R.S. Abagyan, 2011, published in Zhurnal Prikladnoi Khimii, 2011, Vol. 84,
No. 3, pp. 408–414.
ORGANIC SYNTHESIS AND INDUSTRIAL
ORGANIC CHEMISTRY
Thermodynamic and Kinetic Aspects
of a Single-Reactor Synthesis
of 5-Amino-3-methyl-1,2,4-triazole Hydrochloride
from Aminoguanidine and Acetic Acid
E. V. Tarasova, V. M. Chernyshev, A. V. Chernysheva, and R. S. Abagyan
South-Russian State Technical University (Novocherkassk Polytechnic Institute),
Novocherkassk, Rostov-on-Don oblast, Russia
Received August 13, 2010
Abstract—Fundamental thermodynamic and kinetic aspects of the reaction in which acetic acid guanyl
hydrazide is formed from aminoguanidine and acetic acid in aqueous solutions at pH 0.6–1.5 and the kinetics of
cyclization of acetic acid guanyl hydrazide hydrochloride to 5-amino-3-methyl-1,2,4-triazole hydrochloride in a
melt were studied. Methods for synthesis of acetic acid guanyl hydrazide hydrochlorides and 5-amino-3-
methyl-1,2,4-triazole hydrochloride were developed.
DOI: 10.1134/S1070427211030116
Carboxylic acid guanyl hydrazides are widely used
for synthesis of 3-substituted 5-amino-1,2,4-triazoles
[1–8]. One of the most important methods for syn-
thesis of guanyl hydrazides and 3-substituted 5-amino-
1,2,4-triazoles is the reaction of amino-guanidine with
carboxylic acids [5–15]. It is believed that, depending
on conditions, this reaction can yield both guanyl
hydrazides [4–9] and 3-substituted 5-amino-1,2,4-
triazoles [10–15]. In the latter case, it is assumed that
the guanyl hydrazides being formed are cyclized into
aminotriazoles in the course of the reaction. Despite
the wide use of the reaction of aminoguanidine with
carboxylic acids for synthesis of aminotriazoles, its
fundamental kinetic and thermo-dynamic aspects and
the effect of synthesis conditions on the reaction
direction has long remained poorly understood.
Recently, the kinetic and thermodynamic aspects of
the reaction of aminoguanidine with malonic acid in
aqueous solutions have been studied and the synthesis
conditions of 5-amino-3-carboxymethyl-1,2,4-triazole
and bis-5-amino-1,2,4-triazol-3-ylmethane have been
optimized [8]. In order to further analyze the reaction
of aminoguanidine with carboxylic acids and optimize
this method for synthesis of 3-substituted 5-amino-
1,2,4-triazoles, we examined in the present study the
fundamental kinetic and thermodynamic aspects of the
reaction in which acetic acid guanyl hydrazide
hydrochloride (GH) is formed from aminoguanidine
(AG) and acetic acid (AcOH) in acid aqueous solutions
and the kinetics of GH cyclization into 5-amino-3-
methyl-1,2,4-triazole hydrochloride (AMT) in a melt:
Cl _
NH2 + H2O
H
O
NH2
O
H
N
H+/H2O
N
N
H2N
+
NH2
Cl_
H2O
+
+
N
CH3
Cl_
H2N
N
H
HO
CH3
H
N
H
NH2
H3C
AMT
AcOH
GH
AG
400

THERMODYNAMIC AND KINETIC ASPECTS
401
The above sequence of reactions can yield 3-
substituted 5-amino-1,2,4-triazoles (in the form of
salts) in a single-reactor process, with bypassed stages
of isolation of guanyl hydrazides and their cyclization
in a free form [3] or under the action of alkalis [4–9].
In technological regard, this must diminish the amount
of wastewater and waste inorganic salts.
taken to be equal to the analytical concentration of
AcOH because the degree of dissociation of acetic acid
is negligible (pKa 4.6 [17]) under these conditions.
The concentrations [GH], [AcOH], and [AG] in
Eq. (1) were determined by analyzing the composition
of the reaction mixtures after equilibrium was attained.
The equilibrium state was reached from the sides of
both forward and reverse reactions until the
concentrations being analyzed coincided within the
experimental error. The reaction mixtures necessary
for studying the reverse reaction were obtained by
heating AG, AcOH, and HCl in the minimum amount
of water at 60°C for 6 h. Under these conditions, the
yield of guanyl hydrazides markedly exceeded the
equilibrium yield in dilute solutions. Then the resulting
mixture was diluted with water to a required volume
and the hydrolysis of GH was studied.
EXPERIMENTAL
We used aminoguanidine hydrocarbonate (Merck)
with the main substance content of no less than 98%;
the rest of the reagents were of chemically pure grade.
Twice distilled water was used to prepare aqueous
solutions.
Experiments for analysis of the reaction of GH
formation were performed as described in [7]. The
reactor temperature was maintained to within ±0.5°.
The solution acidity was determined with a Mettler
Toledo S40-KS instrument equipped with an
InLab®Expert Pro combined electrode. The AG con-
centration cAG (M) in reaction mixtures was deter-
mined by iodatometric titration [7]. The GH concentra-
tion was calculated by the formula
Experiments devoted to a study of the fundamental
kinetic aspects of the reaction of GH cyclization into
AMT were performed in 15-ml test tubes, each
charged with 0.1 g of GH. The temperature of the
reaction mixtures was maintained constant within
±0.5° with a thermostat having the form of an oil bath
placed on an IKA RCT basic magnetic rabble with a
heater, equipped with an external thermocouple. The
test tubes with the reaction mixture were kept in the
thermostat for the required time, and then the reaction
mixture was dissolved in 40 ml of a 0.025 M KH2PO4
solution and the AMT concentration was determined.
The AMT concentration was analyzed by high-
performance liquid chromatography (HPLC) on a
Milikhrom-5.3 chromatograph with a UV detector
(80×2 mm column packed with Separon C18 sorbent,
0.025 M aqueous solution of KH2PO4 as mobile phase,
elution rate 80 μl min–1, detection at a wavelength of
210 nm, sample volume 6 μl, chromatographic column
temperature 35°C). The elution time of AMT was
5.1 min. The pKa of acetic acid guanyl hydrazide was
determined by potentiometric titration of GH with a
0.1 N solution of KOH by the method described in [17].
cGH = cAG,0 – cAG
,
where cAG,0 and cAG are the initial and running
concentrations of AG in the reaction mixture (M).
The AcOH concentration cAcOH (M) was calculated
by the formula
cAcOH = cAcOH,0 – cGH
,
where cAcOH,0 is the initial concentration of AcOH.
The equilibrium constants of the reaction of GH
formation, KGH, were calculated by the formula
[GH]
,
[AcOH] [AG]
KGH
=
(1)
where [GH], [AcOH], and [AG] are the equilibrium
concentrations of the reactants (M).
As it was done in [7], we assumed in our kinetic
and thermodynamic calculations that aminoguanidine
reacts in the form of an aminoguanidinium cation
(AG). Under the conditions of our experiments, the
concentration cAG is almost equal to the analytical
concentration of aminoguanidine because, in the pH
range under study (0.6–1.5), the concentration of the
unprotonated form of aminoguanidine is negligible
(pKa 11.5 [16]). The concentration cAcOH was also
NMR spectra were recorded with a Bruker Avance
600 spectrometer (600 MHz for1H and 150 MHz for
13C, DMSO-d6 as solvent and TMS as internal
standard), and mass spectra, using a Finnigan MAT
Incos 50 instrument (direct introduction of a sample
into the ionic emission source with an ionization
energy of 70 eV). An elemental analysis was made
with a Perkin–Elmer analyzer. The melting points were
determined in sealed capillaries with a PTP instrument.
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402
TARASOVA et al.
Acetic acid 2-guanyl hydrazide hydrochloride
(Irel, %): 98 [M – HCl]+ (54), 57 (46), 42 (100). Found
(%): С 27.01, Н 5.18, N 41.39; М 134.7 (poten-
tiometric titration). C3H7N4Cl. Calculated (%): C
26.78, H 5.24, N 41.63; М 134.57.
(GH). A mixture of 30 g (0.220 mol) of amino-
guanidine hydrocarbonate, 26.77 g (0.242 mol) of a
33% solution of HCl, and 39.64 g (0.660 mol) of
AcOH was boiled under agitation for 1 h and the
excess amount of AcOH was evaporated in a vacuum.
A 100-ml portion of 2-propanol was added to the
residue and the mixture was boiled under agitation for
5 min and cooled to 0–5°C. The precipitate formed
was filtered off, recrystallized from 2-propanol, and
dried at 70°C. Yield 20.1–22.5 g (60–67%), mp 138–
For adequate determination of the equilibrium
constants of the reaction of GH formation from AG
and AcOH by analysis of concentrations of the equilib-
rium mixtures, it was necessary to make sure that the
reaction of GH cyclization into AMT does not occur in
the conditions under study. An HPLC analysis of the
reaction mixtures demonstrated the absence of AMT,
i.e., the GH cyclization does not occur in acid aqueous
solutions (pH 0.6–1.5) at temperatures of up to 100°C
and does not hinder equilibration. The equilibrium
constants KGH obtained at temperatures of 40–80°C are
presented below:
1
1
139°C. H NMR spectrum, Н, δ, ppm: 1.87 s (3H,
CH3), 7.87 br.s (4H, 2NH2), 9.53 с (1H, NH), 10.10 s
(1H, NH). 13С NMR spectrum, δ, ppm: 20.77 q (CH3,
J = 128.8 Hz), 158.80 s (С=N), 169.73 m (CO). Mass
spectrum, m/z (Irel, %): 116 [M – HCl]+ (13), 98 (29),
73 (14), 57 (21), 43 (100). Found (%): С 23.28, Н
6.07, N 36.51; М 152.3 (potentiometric titration).
C3H9N4OCl. Calculated (%): C 23.61, H 5.95, N
36.72; М 152.58.
T, °C
K
GH, l mol–1
40
50
10.7±0.3
6.3±0.18
5-Amino-3-methyl-1,2,4-triazole hydrochloride
(AMT). A mixture of 13.6 g (0.10 mol) of amino-
guanidine hydrocarbonate, 12.17 g (0.11 mol) of a
33% solution of HCl, and 18.1 g (0.30 mol) of AcOH
was heated to 115–120°C under agitation for 1 h,
AcOH was evaporated, and the reaction mixture was
heated to 180–190°C and kept at this temperature for
2 h. The resulting melt was cooled to 50–60°C and
20 ml of ethyl acetate was added. The mixture was
boiled with reflux for 3–5 min and then was cooled.
The crystalline precipitate was filtered off and dried at
70°C. We obtained 12.6–12.9 g of AMT, with a
content of the main substance of 96–97% (yield 90–
93%) according to HPLC data. After recrystallization
from 30 ml of 2-propanol, the yield of the analytically
pure product was 8.9–9.4 g (66–70%), mp 135–137°C.
1H NMR spectrum, δ, ppm: 2.20 s (3H, CH3), 8.01 br.s
(2H, NH2). 13С NMR spectrum, δ, ppm: 10.87 q (CH3,
J = 131.0 Hz), 147.42 t (C-3 of triazole, J = 7.7 Hz),
151.11 s (C-5 of triazole). Mass spectrum (EI), m/z
60
70
80
4.6±0.12
3.5±0.14
2.6±0.10
Upon changes in acidity within the range under
study, KGH remained unchanged within the experi-
mental error. The linear dependence of logarithms of
KGH on inverse temperature made it possible to apply
van’t Hoff’s isobar equation to calculate the heat effect
of the reaction of GH formation to be ΔHGH = –31.5 ±
2 kJ mol–1. This value is close to enthalpies of similar
reactions in which malonic acid guanyl hydrazide is
formed from aminoguanidine and malonic acid
(–27.5 ± 2.0 kJ mol–1) and malonic acid diguanyl
hydrazide is formed from aminoguanidine and malonic
acid guanyl hydrazide (–34.6 ± 5.3 kJ mol–1) [7].
The kinetics of the reaction of GH formation was
studied in the reagent concentration range 0.3–1.0 M
and pH 0.6–1.5. When processing kinetic data, we
HO OH
HO OH
H
H
H
H2N
N
H2N
N
NH2 + AcOH + H3O+
H2N
N
+
H2O
N
CH3
N
H
CH3
NH2
AG
NH
2 H
H
NH2
TI
k1
k-1
GG + H2O + H3O+.
H3O
+
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 84 No. 3 2011

THERMODYNAMIC AND KINETIC ASPECTS
403
were based on the assumption that this reaction occurs
by the mechanism that is characteristic of reactions
between amines and carboxylic acids under acid
catalysis conditions [18, 19] and is similar to that of
the reaction of aminoguanidine with malonic acid [7].
Because the reaction is performed in dilute aqueous
solutions, it has a pseudozeroth order with respect to
H2O. Therefore, the rate constant of the reverse
reaction can be expressed in terms of k'–1 = k–1c(H2O).
At a constant pH, Eq. (2) takes the form
With this mechanism, the reaction rate must be
described, irrespective of which stage, formation of a
tetrahedral intermediate (TI) or its hydrolysis [18], is
rate determining, by the kinetic equation
(dcGH)/(dτ) = k'1 cAGcAcOH – k''–1cGH
,
where k'1 = k1c(H3O+) and k''–1 = k'–1c(H3O+) are the
effective rate constants of the forward and reverse
reactions, respectively.
(dcGH)/(dτ) = k1cAGcAcOHc(H3O+)
The constant k'1 was calculated by the linear least-
squares method, with the integral form of the kinetic
equation used for the reversible bimolecular reaction
[20]
– k–1cGHc(H2O)c(H3O+),
(2)
where k1 and k2 are the rate constants of the forward
and reverse reactions, respectively.
(cAG,0 − X1)(cAG − X2)
1
k'1
1
,
ln
τ =
X1 − X2
(cAG,0 − X2)(cAG − X1)
[KGH(cAcOH,0 − cAG,0) + 2cAG,0] √[KGH(cAcOH,0 − cAG,0) + 2cAG,0]2+4(KGH − 1)c2AG,0
.
X1,2
=
2(KGH − 1)
The rate constant of the reverse reaction, k''–1, was
found from the relation k''–1 = k'1/KGH.
aminoguanidine and acetic acid is substantially lower
than that of a similar reaction of aminoguanidine with
malonic acid (42.1 ± 3 kJ mol–1) [7]. Explaining the
influence exerted by the structure of carboxylic acid on
the activation energy requires an additional study of
the reaction under discussion for the example of other
carboxylic acids.
The adequacy of the chosen kinetic model to the
experimental data was assessed by calculating Fisher’s
criterion. The calculated values of Fisher’s criterion
did not exceed the tabulated data for the 95%
probability in the whole range of experimental data
[20], which points to adequacy of the chosen kinetic
model to the experimental data and does not contradict
the suggested reaction mechanism.
When processing the kinetic data for the reaction of
GH cyclization into 5-amino-3-methyl-1,2,4-triazole
hydrochloride, we assumed that the volume of the
It can be seen in Fig. 1 that, in the pH range under
study, is directly proportional to the concentration
c(H3O+). A similar dependence of k'1 and k'–1 on
c(H3O+) is observed at other temperatures. This serves
as evidence in favor of the suggested mechanism and
makes it possible to calculate the rate constants k1 and
k'–1 (Table 1).
The linear dependence of the logarithms of the
constants k1 and k'–1 on inverse temperature (Fig. 2)
made it possible to calculate parameters of the
Arrhenius equation k = Aexp (–Ea/RT) to be ln A =
6.02 ± 0.06 and Ea = 24.3 ± 0.2 kJ mol–1 for the
forward reaction and ln A = 15.8 ± 0.1 and Ea = 55.8 ±
0.4 kJ mol–1 for the reverse reaction. It is significant
that the activation energy of the reaction between
c(H3O+), M
Fig. 1. Dependence of (1) k1' and (2) k–1' on c(H3O+) at 60°C.
(k1') Effective rate constant of the forward reaction and
(k–1'') effective rate constant of the reverse reaction.
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 84 No. 3 2011

404
TARASOVA et al.
reaction mixture remains unchanged in the course of
the reaction. The experimental data are best described
by a first-order kinetic equation of the reaction:
The revealed fundamental thermodynamic and
kinetic aspects of the reactions make it possible to
formulate basic approaches to optimization of the GH
synthesis and single-reactor synthesis of AMT from
AG and AcOH. It is advisable to synthesize GH under
acid catalysis conditions at pH ≤ 1. To raise the
equilibrium yield of GH, it is appropriate to use an
excess amount of acetic acid and to perform the
synthesis with the minimum amount of water in the
reaction mixture (similarly to the conditions suggested
in [8]). The high activation energy of the reaction of
AMT cyclization results in that the rate of GH
cyclization is very low at temperatures of up to 140°C.
Therefore, a selective synthesis of GH can be
performed at the boiling point of the reaction mixture
(~120°C). However, synthesis of AMT requires that
GH should be cyclized at temperatures T ≥ 140°C.
Thus, to obtain AMT, it is advisable to perform the
first stage of synthesis at the boiling point of the
reaction mixture and, to pass to the second state, it is
advisable to evaporate acetic acid and water released in
the course of the reaction and to heat GH formed to a
temperature exceeding 140°C.
(dnAMT)/(dτ) = knGH
,
where k is the rate constant (s–1), and nAMT and nGH,
molar amounts of AMT and GH in the reaction
mixture.
nAMT was found using HPLC, and nGH was
calculated by the formula
nGH = nGH,0 – nAMT
,
where nGH,0 is the initial molar amount of GH.
We calculated the rate constants k by the least-
squares method, using the integral form of a first-order
kinetic equation [20]. The values of k, found at various
temperatures, are presented below:
T, °C
150
160
180
200
k, min–1
0.0016±0.0001
0.0053±0.0003
0.024±0.003
0.099±0.006
Because hydrocarbonate (AGH) is the best
available salt of aminoguanidine, we used this sub-
stance as a raw material when developing a single-re-
actor synthesis of GH and AMT. The required acidity
of the reaction mixture was created with concentrated
hydrochloric acid (HCl content 33%).
A calculation of Fisher’s criterion demonstrated the
adequacy of the chosen kinetic model to the
experimental data.
The linear dependence of ln k on inverse tempera-
ture makes it possible to calculate the parameters of
the Arrhenius equation: ln A = 31.9 ± 0.2 and Ea =
134.3 ± 0.8 kJ mol–1.
Let us consider the effect of technological
parameters on the yield of GH and AMT.
Mixing the reagents gives a mixture of AG, AcOH,
and H2O. The subsequent boiling of the resulting
mixture (temperature 118–120°C) gradually yields
GH. It is inappropriate to use a >10% molar excess of
HCl with respect to the stoichiometric amount of
AGH, because this fails to cause a noticeable increase
in the reaction rate (Fig. 3). Raising the AcOH : AGH
molar ratio to more than 3 : 1 does not lead to any
significant rise in the equilibrium conversion of AG
(Table 2). Therefore, to obtain GH, it is appropriate to
use the molar ratio AGH : HCl : AcOH = 1 : 1.1 : 3 at
a synthesis duration of 2 h. On evaporating the excess
amount of acetic acid in a vacuum and crystallization
from 2-propanol, we obtained an analytically pure GH
in 60–67% yield.
Fig. 2. Logarithms of the rate constants of (1) forward and
(2) reverse reactions vs. the inverse temperature T–1 (K–1).
(k1) Rate constant of the forward reaction and (k'–1) rate
constant of the reverse reaction.
In a single-reactor synthesis of AMT, it is
worthwhile to evaporate acetic acid under atmospheric
pressure and heat GH to 180–190°C. It is inappropriate
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THERMODYNAMIC AND KINETIC ASPECTS
405
Table 1. Rate constants k1 and k'–1 at various temperatures
Table 2. Effect of the initial AGH : AcOH ratio on the AG
conversion α at 120°C. Molar ratio AGH : HCl = 1 : 1.1
T, °C
k1, M–2 min–1
k'–1, M–1 min–1
α, %, at indicated synthesis duration, min
AGH:AcOH,
mol : mol
5
10
62
85
88
92
95
20
70
89
94
96
97
40
78
90
94
97
98
60
83
91
95
97
98
120
83
91
95
97
98
40
50
60
0.034±0.003
0.051±0.004
0.068±0.002
0.0032±0.0004
0.0081±0.0009
0.0148±0.0008
1:1.2
1:1.7
1:2.0
1:3.0
1:4.0
41
78
83
89
91
70
80
0.079±0.005
0.102±0.005
0.0227±0.0023
0.0394±0.0034
to raise the temperature to above 190°C because of the
partial decomposition of the product and its more
difficult purification. At temperatures below 180°C,
the cyclization reaction is too slow. The suggested
variant of single-reactor synthesis can produce AMT in
90–93% yield and main substance content of no less
than 96%.
salt forms of guanyl hydrazides of aliphatic carboxylic
acids with an acceptable rate is only possible at com-
paratively high temperatures (≥140°C). This enables
selective synthesis of salt forms of carboxylic acid 2-
guanyl hydrazides from aminoguanidine and car-
boxylic acids in acid aqueous solutions at tem-
peratures of 100–120°C.
The compounds GH and AMT can exist in several
(3) To provide a high yield, it is preferable to
perform the first stage of the single-reactor synthesis of
5-amino-3-methyl-1,2,4-triazole at a molar ratio amino-
guanidine hydrocarbonate : acetic acid : hydrochloric
acid = 1 : 1.1 : 3 at 118–120°C; it is advisable to
cyclize acetic acid 2-guanyl hydrazide after evapora-
1
tautomeric forms. As indicated by H NMR and 13C
proton-coupled NMR spectra and in accordance with
the acid-base properties (pKBH 8.68 ± 0.05 at 22°C),
+
the structure of GH is presumably similar to that of
other salts of carboxylic acid 2-guanyl hydrazides [21.
The predominant AMT tautomer in a solution in
dimethylsulfoxide is 5-amino-3-methyl-1,2,4-triazo-
lium chloride. This is indicated by the chemical shifts
of carbon atoms of the triazole ring in the 13C NMR
spectrum, whose signals are characteristic of 5-amino-
1,2,4-triazolium salts [22].
α, %
CONCLUSIONS
(1) The reaction in which acetic acid guanyl
hydrazide is formed from aminoguanidine and acetic
acid in acid aqueous solutions is acid-catalyzed,
reversible and exothermic and is first-order with
respect to CH3COOH, aminoguanidinium cation, and
H3O+. The suggested mechanism of this reaction is
similar to that of the reaction of amines with
carboxylic acids under acid-catalysis conditions, but a
monoprotonated form of aminoguanidine serving as a
nucleophile.
τ, min
(2) The reaction of thermal cyclization of acetic
acid guanyl hydrazide hydrochloride is described by a
first-order kinetic equation and has a high activation
energy (134.3 ± 0.8 kJ mol–1). Thus, the cyclization of
Fig. 3. AG conversion α vs. time τ at a temperature of 120°C.
Molar ratio AGH : HCl : AcOH: (1) 1 : 1 : 1, (2) 1 : 1.03 :
1, (3) 1 : 1.05 : 1, (4) 1 : 1.08 : 1, (5) 1 : 1.1 : 1, and
(6) 1 : 1.2 : 1.
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TARASOVA et al.
9. Chipen, G.I. and Grinshtein, V.Ya., Izv. Akad. Nauk
LatvSSR, 1965, no. 2, pp. 204–208.
10. Chupakhin, O.N., Ulomsky, E.N., Deev, S.L., and
Rusinov, V.L., Synth. Commun., 2001, vol. 31, no. 15,
pp. 2351–2355.
tion of the excess amount of acetic acid at tempera-
tures of 180–190°C.
ACKNOWLEDGMENTS
11. Reilly, J. and Drumm, P.J., J. Chem. Soc., 1926, vol. 50,
pp. 1729–1737.
12. Atkinson, M.R., Kozmak, A.A., Parkes, E.A., and
Polya, J.B., J. Chem Soc., 1954, vol. 78, no. 12, pp. 4508–
4510.
13. Barnett, E.D.B., Goodway, N.F., Kermack, W.O., et al.,
J. Chem. Soc., 1929, vol. 53, pp. 813–816.
14. Lipinski, C.A., J. Med. Chem., 1983, vol. 26, no. 1,
pp. 1–6.
15. Lopyrev, V.A. and Rakhmatullina, T.N., Zh. Obshch.
Khim., 1982, vol. 53, no. 7, p. 1684.
16. Koskinen, M., Mutikainen, I., Tilus, P., et al., Monatsh.
Chem., 1997, vol. 128, nos. 8–9, pp. 767–775.
17. Al’bert, A. and Serzhent, E., Konstanty ionizatsii kislot i
osnovamii (Constants of Acids and Bases Ionizations),
Miscow: Khimiya, 1964.
18. Brown, R.S., Bennet, A.J., and Slebocka-Tilk, H., Acc.
Chem. Res., 1992, vol. 25, no. 11, pp. 481–488.
19. Pan, B., Ricci, M.S., and Trout, B.L., J. Phys. Chem. B,
2010, vol. 114, no. 13, pp. 4389–4399.
20. Lebedev, N.N., Manakov, M.N., and Shvets, V.F.,
Teoriya tekhnologicheskikh protsessov osnovnogo
organicheskogo i neftekhimicheskogo sinteza (Theory of
Technological Processes of Basic Organic and
Petrochemical Synthesis), Moscow: Khimiya, 1975.
21. Chernyshev, V.M., Chernysheva, A.V., Tarasova, E.V.,
et al., Acta Cryst. Sect. E, 2010, vol. 66, pp. 1152–1153.
22. Anders, E., Wermann, K., Wiedel, B., and Vanden
Eynde, J.-J., Liebigs. Ann., 1997, no. 4, pp. 745–752.
The study was financially supported by the RF
Ministry of Education and Science under the Federal
target program “Scientific and Scientific-Pedagogical
Personnel of Innovative Russia” (contract P1472,
project NK-186P/3).
REFERENCES
1. Temple, C., Chemistry of Heterocyclic Compounds,
vol. 37, Montgomery, J.A., Ed., New York: Wiley,
1981, pp. 103–204.
2. Curtis, A.D.M., Sci. Synth., 2004, vol. 13, pp. 603–639.
3. Dolzhenko, A.V., Pastorin, G., Dolzhenko, A.V., and
Chui, W.-K., Tetrahedron Lett., 2009, vol. 50, no. 18,
pp. 2124–2128.
4. Grinshtein, V.Ya. and Chipen, G.I., Zh. Obshch. Khim.,
1961, vol. 31, no. 3, pp. 886–890.
5. Huang, Y., Hu, X.-Q., Shen, D.-P., and Fei, Y., Mol.
Divers., 2007, vol. 11, no. 2, pp. 73–80.
6. Abdel-Megeed, A.M., Abdel-Rahmana, H.M., Alkara-
manya, G.-E.S., and El-Gendya, M.A., Eur. J. Med.
Chem., 2009, vol. 44, no. 1, pp. 117–123.
7. Chernysheva, A.V., Chernyshev, V.M., Korolenko, P.V.,
and Taranushich, V.A., Zh. Prikl. Khim., 2008, vol. 81,
no. 10, pp. 1690–1695.
8. Chernyshev, V.M., Chernysheva, A.V., and Taranu-
shich, V.A., Zh. Prikl. Khim., 2009, vol. 82, no. 2,
pp. 282–287.
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