Russian Chemical Bulletin, International Edition, Vol. 50, No. 5, pp. 820822, May, 2001820
1066-5285/01/5005-820 $25.00 © 2001 Plenum Publishing Corporation
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 784786, May, 2001.
Hydrolysis of some imidazole, benzimidazole, and 1,2,3-benzotriazole
derivatives according to HPLC and NMR diffusimetry data
Yu. L. Polyakova,
A. V. Bulanova,
and R. Sh. Vartapetyan
Samara State University,
1 ul. Akad. Pavlova, 443011 Samara, Russian Federation.
Fax: +7 (846 2) 34 5417. E-mail: email@example.com
Institute of Physical Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 952 0065. E-mail: firstname.lastname@example.org
Hydrolysis of 1-mesylimidazole, 1-mesylbenzotriazole, and 1-tosylbenzimidazole was
studied by reversed-phase HPLC and pulsed field gradient NMR diffusimetry. The hydrolysis
rate constants and half reaction times were determined. The self-diffusion coefficients of the
substances in aqueous solutions were measured. The reversed-phase HPLC data agree well
with those of NMR diffusimetry.
Key words: hydrolysis, hydrolysis rate constant, self-diffusion coefficients, biologically
active substances, reversed-phase HPLC, NMR diffusimetry.
Chromatography becomes a more promising method
of physicochemical studies of various substances and
biological objects, which is due to apparatus and me-
thodical improvement of variants of the method and
development of new high-quality sorbents.
The purpose of this work was to study the interrela-
tion between the structure and physicochemical proper-
ties of substances and the behavior in aqueous solutions
of N-sulfonyl-substituted derivatives of some hetero-
cycles, 1-mesylimidazole (1), 1-tosylbenzimidazole (2),
and 1-mesylbenzotriazole (3), by reversed-phase HPLC
and NMR diffusimetry.*
These objects for studying were chosen because a
series of drugs used for various diseases was synthe-
sized from five-membered nitrogen-containing hetero-
As shown in Ref. 9, N-tosylbenzimidazole
(2) possesses an antibacterial activity. Therefore, it is
probable that other similar derivatives of five-membered
nitrogen-containing heterocycles can be biologically ac-
tive. The study of the capability of hydrolysis in aqueous
solutions with the pH close to that in biological liquids
will help to forecast the behavior of these compounds in
Since molecular weights of the starting substances
and hydrolysis products should differ, it is reasonable to
assume that the hydrolysis process can conveniently be
monitored using self-diffusion of molecules in solutions:
the values of self-diffusion coefficients (SDC), under
other equivalent conditions, are determined by the weight
of diffusing particles. The study of self-diffusion, in
particular, by NMR diffusimetry, can provide an addi-
tional fruitful information on the physicochemical prop-
erties of liquids.
Chromatographic studies were performed using a Milikhrom-
4 liquid chromatograph (Russia) with a UV-spectrometric de-
tector at λ = 190 and 220 nm. A column 80 mm long with an
inner diameter of 2 mm was packed with silica gel (Separon
SGX RPS) with grafted octadecyl groups (specific surface
, particle size 57 µm). Bidistilled water served as
an eluent. The mobile phase velocity was 100 µL min
Current concentrations of the starting substances and hydrolysis
products were calculated by the peak surface areas in the
chromatograms obtained in experiments.
Compounds 13 were synthesized according to a previ-
ously described procedure.
Substances were identified by
retention times of the hydrolysis products.
Hydrolysis of 1-mesylimidazole (1), 1-tosylbenzimidazole
(2), and 1-mesylbenzotriazole (3) was performed as follows. A
buffer solution (2 mL) (a mixture of orthophosphoric (0.1 M),
acetic (0.1 M), and boric acids (0.05 Ì) with the addition of an
aliquot of a 0.2 M solution of sodium hydroxide (all substances
were analytically pure grade)) with an exact pH was added to a
freshly prepared 1% solution (2 mL) of a substrate.
solutions with pH 4.0, 7.0, 8.0, and 9.0 were used. The time of
pouring together the solutions was fixed. Samples were taken
and chromatographed at certain intervals. The last chromato-
graphic measurement was performed 24 h after the beginning of
the reaction. To estimate the accuracy of quantitative measure-
ments and reproducibility of the obtained results, substances
were hydrolyzed five times at a specified pH. The final products
were identified by retention times of standard substances. The
relative error of a single measurement did not exceed 5%. (The
experimental error was determined specifying the degree of
reliability according to Student P = 0.95).
The reaction of a pseudo-first order was observed due to an
excess of a reactant (H
* The NMR method with pulsed magnetic field gradient (PFG
NMR) is implied by NMR diffusimetry.